* 141900

HEMOGLOBIN--BETA LOCUS; HBB


HGNC Approved Gene Symbol: HBB

Cytogenetic location: 11p15.4     Genomic coordinates (GRCh38): 11:5,225,464-5,227,071 (from NCBI)


Gene-Phenotype Relationships
Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
11p15.4 {Malaria, resistance to} 611162 3
Delta-beta thalassemia 141749 AD 3
Erythrocytosis, familial, 6 617980 AD 3
Heinz body anemia 140700 AD 3
Hereditary persistence of fetal hemoglobin 141749 AD 3
Methemoglobinemia, beta type 617971 AD 3
Sickle cell disease 603903 AR 3
Thalassemia-beta, dominant inclusion-body 603902 AD 3
Thalassemia, beta 613985 3

TEXT

Description

The alpha (HBA1, 141800; HBA2, 141850) and beta (HBB) loci determine the structure of the 2 types of polypeptide chains in adult hemoglobin, HbA. Mutant beta globin that sickles causes sickle cell disease (603903). Absence of beta chain causes beta-zero-thalassemia. Reduced amounts of detectable beta globin causes beta-plus-thalassemia. For clinical purposes, beta-thalassemia (613985) is divided into thalassemia major (transfusion dependent), thalassemia intermedia (of intermediate severity), and thalassemia minor (asymptomatic).


Gene Structure

Fine detail of both the mouse (Miller et al., 1978) and the human beta-globin gene was determined in the 1970s (Flavell et al., 1978). The mouse beta-globin gene is interrupted by 2 intervening sequences of DNA that divide it into 3 discontinuous segments. The entire gene, including the coding, intervening and untranslated regions, is transcribed into a colinear 15S mRNA precursor. Because mature globin mRNA is smaller (10S) and does not contain the intervening sequences, the 15S precursor must be processed.

Using restriction endonucleases and recombinant DNA techniques, Flavell et al. (1978) prepared a map of the human beta- and delta- (142000) globin genes. The beta-globin gene contains a nonglobin DNA insert about 800-1000 basepairs in length, present within the sequence coding for amino acids 101-120. A similar untranscribed sequence may be present in the delta gene.


Mapping

Use of a combination of somatic cell hybridization and hybridization of DNA probes permitted assignment of the beta hemoglobin locus to chromosome 11 (Deisseroth et al., 1978). Parallel experiments showed that the gamma globin genes (HBG1, 142200; HBG2, 142250) are also on chromosome 11, a result to be expected from other data indicating linkage of beta and gamma.

Flavell et al. (1978) found that the distance between the beta and delta genes is about 7,000 nucleotide pairs and that the delta gene is to the 5-prime side of the beta gene, as predicted by other evidence. Polymorphism was found at the third nucleotide of the codon for amino acid number 50 (Wilson et al., 1977).

The order of the genes in the beta-globin cluster was proved by restriction enzyme studies (Fritsch et al., 1979); starting with the 5-prime end, the order is gamma-G--gamma-A--delta--beta--Hpa I. By 'liquid' molecular hybridization, Haigh et al. (1979) studied mouse-man hybrid rearrangements involving chromosome 11 and assigned the nonalpha-globin cluster to the region 11p11-p15.

Housman et al. (1979) concluded from study of Chinese-hamster ovary cell lines containing chromosome 11 or selected parts thereof that the beta hemoglobin complex (NAG, nonalpha-globin genes) is in interband p1205-p1208.

Lebo et al. (1981) studied the linkage between 2 restriction polymorphisms, the HpaI polymorphism on the 3-prime side of the beta-globin gene and the SacI polymorphism on the 5-prime side of the insulin gene. They found 4 recombinants in 34 meioses (12%), giving 90% confidence limits for the interval as 6-22 cM.

From in situ hybridization studies, Morton et al. (1984) concluded that the beta-globin gene is situated at 11p15. Their studies included a t(7;11)(q22;p15) in which the beta-globin locus appeared to be at the junction point. Interest relates to the translocation cell line coming from a patient with erythroleukemia and the fact that the ERBB oncogene (131550) is located on chromosome 7 (7pter-q22).

By high-resolution chromosome sorting of human chromosomes carrying segments of chromosome 11 and by spot blotting with various gene-specific probes, Lebo et al. (1985) concluded that the loci for parathyroid hormone, beta-globin, and insulin are all located on 11p15.

By in situ hybridization studies of chromosome 11 rearrangements, Magenis et al. (1985) likewise assigned HBB to 11p15. In an addendum, they referred to studies of a t(7;11) rearrangement that further narrowed the HBB assignment to 11p15.4-11pter.

By high-resolution cytogenetics and in situ hybridization, Lin et al. (1985) placed the beta-globin gene in the 11p15.4-p15.5 segment. Through reanalysis of a Chinese hamster/human cell hybrid that had lost all human chromosomes except 11, Gerhard et al. (1987) reached the conclusion that the beta-globin gene complex is located on 11p15 and that the insulin and HRAS1 genes are located in a segment of DNA approximately 10 Mb long.

Pseudogenes

The eta locus is 1 of 5 ancient beta-related globin genes linked in a cluster, 5-prime--epsilon (142100)--gamma--eta--delta--beta--3-prime, that arose from tandem duplications (Koop et al., 1986). The eta locus was embryonically expressed in early eutherians and persisted as a functional gene in artiodactyls (e.g., goat), but became a pseudogene in proto-primates and was lost from rodents and lagomorphs. Sequence studies show that the goat eta gene is orthologous to the pseudogene located between the gamma and delta loci of primates and called psi-beta-1. (The Hb beta-1 pseudogene (psi-beta-1) can be symbolized HBBP or HBBP1.)


Gene Function

Dye and Proudfoot (2001) performed in vivo analysis of transcriptional termination for the human beta-globin gene and demonstrated cotranscriptional cleavage (CoTC). This primary cleavage event within beta-globin pre-mRNA, downstream of the poly(A) site, is critical for efficient transcriptional termination by RNA polymerase II (see 180660). Teixeira et al. (2004) showed that the CoTC process in the human beta-globin gene involves an RNA self-cleaving activity. They characterized the autocatalytic core of the CoTC ribozyme and showed its functional role in efficient termination in vivo. The identified core CoTC is highly conserved in the 3-prime flanking regions of other primate beta-globin genes. Functionally, it resembles the 3-prime processive, self-cleaving ribozymes described for the protein-encoding genes from the myxomycetes Didymium iridis and Physarum polycephalum, indicating evolutionary conservation of this molecular process. Teixeira et al. (2004) predicted that regulated autocatalytic cleavage elements within pre-mRNAs may be a general phenomenon and that functionally it may provide an entry point for exonucleases involved in mRNA maturation, turnover, and, in particular, transcriptional termination.

It is increasingly appreciated that the spatial organization of DNA in the cell nucleus is a key contributor to genomic function. Simonis et al. (2006) developed 4C technology (chromosome conformation capture (3C)-on-chip), which allowed for an unbiased genomewide search for DNA loci that contact a given locus in the nuclear space. They demonstrated that active and inactive genes are engaged in many long-range interchromosomal interactions and can also form interchromosomal contacts. The active beta-globin locus in the mouse fetal liver preferentially contacts transcribed, but not necessarily tissue-specific, loci elsewhere on chromosome 7, whereas the inactive locus in fetal brain contacts different transcriptionally silent loci. A housekeeping gene in a gene-dense region on chromosome 8 of the mouse, Rad23a (600061), formed long-range contacts predominantly with other active gene clusters, both in cis and in trans, and many of these intra- and interchromosomal interactions were conserved between the tissues analyzed. The data demonstrated that chromosomes fold into areas of active chromatin and areas of inactive chromatin and established 4C technology as a powerful tool to study nuclear architecture.

Schoenfelder et al. (2010) found that mouse Hbb and Hba associated with hundreds of active genes from nearly all chromosomes in nuclear foci that they called 'transcription factories.' The 2 globin genes preferentially associated with a specific and partially overlapping subset of active genes. Schoenfelder et al. (2010) also noted that expression of the Hbb locus is dependent upon Klf1 (600599), while expression of the Hba locus is only partially dependent on Klf1. Immunofluorescence analysis of mouse erythroid cells showed that most Klf1 localized to the cytoplasm and nuclear Klf1 was present in discrete sites that overlapped with RNAII foci. Klf1 knockout in mouse erythroid cells specifically disrupted the association of Klf1-regulated genes within the Hbb-associated network. Klf1 knockout more weakly disrupted interactions within the specific Hba network. Schoenfelder et al. (2010) concluded that transcriptional regulation involves a complex 3-dimensional network rather than factors acting on single genes in isolation.


Biochemical Features

Crystal Structure

Andersen et al. (2012) presented the crystal structure of the dimeric porcine haptoglobin (140100)-hemoglobin complex determined at 2.9-angstrom resolution. This structure revealed that haptoglobin molecules dimerize through an unexpected beta-strand swap between 2 complement control protein (CCP) domains, defining a new fusion CCP domain structure. The haptoglobin serine protease domain forms extensive interactions with both the alpha- and beta-subunits of hemoglobin, explaining the tight binding between haptoglobin and hemoglobin. The hemoglobin-interacting region in the alpha-beta dimer is highly overlapping with the interface between the 2 alpha-beta dimers that constitute the native hemoglobin tetramer. Several hemoglobin residues prone to oxidative modification after exposure to heme-induced reactive oxygen species are buried in the haptoglobin-hemoglobin interface, thus showing a direct protective role of haptoglobin. The haptoglobin loop previously shown to be essential for binding of haptoglobin-hemoglobin to the macrophage scavenger receptor CD163 (605545) protrudes from the surface of the distal end of the complex, adjacent to the associated hemoglobin alpha-subunit. Small-angle x-ray scattering measurements of human haptoglobin-hemoglobin bound to the ligand-binding fragment of CD163 confirmed receptor binding in this area, and showed that the rigid dimeric complex can bind 2 receptors.


Molecular Genetics

Beta-Thalassemias

The beta-thalassemias were among the first human genetic diseases to be examined by means of new techniques of recombinant DNA analysis. In general, the molecular pathology of disorders resulting from mutations in the nonalpha-globin gene region is the best known, this elucidation having started with sickle cell anemia in the late 1940s. Steinberg and Adams (1982) reviewed the molecular defects identified in thalassemias: (1) gene deletion, e.g., of the terminal portion of the beta gene (Orkin et al., 1979); (2) chain termination (nonsense) mutations (Chang and Kan, 1979; Trecartin et al., 1981); (3) point mutation in an intervening sequence (Spritz et al., 1981; Westaway and Williamson, 1981); (4) point mutation at an intervening sequence splice junction (Baird et al., 1981); (5) frameshift deletion (Orkin and Goff, 1981); (6) fusion genes, e.g., the hemoglobins Lepore; and (7) single amino acid mutation leading to very unstable globin, e.g., Hb Vicksburg (beta leu75-to-ter).

Since it had been shown by cDNA-DNA hybridization that some cases of severe alpha-thalassemia result from deletion of all or most of the alpha globin genes, Ottolenghi et al. (1975) applied similar techniques to a study of whether beta genes were present in the forms of beta-thalassemia with no synthesis of beta chains. They studied material from persons heterozygous for beta-zero-thalassemia and delta-beta-thalassemia and concluded that at least one of the haploid genomes in this patient had a substantially intact beta globin gene. The beta globin structural gene is intact in beta-zero-thalassemia (Kan et al., 1975) but deleted in both hereditary persistence of fetal hemoglobin (Kan et al., 1975) and delta-beta-thalassemia (Ottolenghi et al., 1975); see 141749.

The possibility that the genetic lesions in beta-plus-thalassemia lie at splicing sites within intervening sequences of the beta globin gene was discussed by Maquat et al. (1980). Beta-zero-thalassemia is heterogeneous. Some cases have absent beta-globin mRNA. Some have a structurally abnormal beta-globin mRNA, usually in reduced amounts. Baird et al. (1981) found a nucleotide change at the splice junction at the 5-prime end of the large intervening sequence (IVS2) as the defect in 3 cases (1 Italian; 2 Iranian).

In a family of Scottish-Irish descent, Pirastu et al. (1983) studied a new type of gamma-delta-beta thalassemia. The proposita presented with hemolytic disease of the newborn which was characterized by microcytic anemia. Initial restriction enzyme analysis showed no grossly abnormal pattern, but studies of polymorphic restriction sites and gene dosage showed extensive deletion of the entire beta-globin cluster. In situ hybridization with radioactive beta-globin gene probes showed that only one 11p homolog contained the beta-globin gene cluster. Kazazian et al. (1982) observed a similar extensive deletion in a Mexican family.

Cai and Kan (1990) demonstrated the usefulness of denaturing gradient gel electrophoresis for detecting beta-thalassemia mutations and suggested that it might be a useful nonradioactive means of detecting mutations in other genetic disorders. Other methods are hybridization with allele-specific oligonucleotide probes, ribonuclease or chemical cleavage, and restriction endonuclease analysis. PCR greatly facilitated implementation of all these detection methods.

Matsuno et al. (1992) invoked possible gene conversion at the chi sequence near the 5-prime end of exon 2 (codons 31-34) as the explanation for the finding of a beta-thalassemia mutation common in southeast Asia (frameshift mutation in codons 41 and 42; see 141900.0326), as well as in Japan, on 2 different restriction frameworks (haplotypes). They presumed that the 6 families found in Japan with this particular mutation had inherited it from ancestors who had migrated to Japan from southeast Asia.

By analysis of family data on 15 restriction site polymorphisms (RSPs), Chakravarti et al. (1984) identified a 'hotspot' for meiotic recombination at the 5-prime end of the beta gene. Recombination leftward (in the 5-prime direction) from a point called chi near the end of the beta-globin gene is 3 to 30 times the expected rate; in the use of RSPs in prenatal diagnosis, it had been assumed that a marker 10 kb from a mutant gene would recombine at a rate of 10(-5) per kb, leading to a diagnostic error of 1 in 10,000. However, their data suggested the error rate using 'loci' on opposite sides of chi may be as high as 1 in 312. By a computer search of the DNA sequences of the beta cluster, they located a chi sequence (5-prime-GCTGGTGG-3-prime) at the 5-prime end of the second intervening sequence of the beta gene. This chi sequence, a promoter of generalized recombination in lambda phage, has been found in high frequency in the mouse genome, especially in immunoglobulin DNA. A recombinational hotspot has been found in the mouse major histocompatibility complex.

In a large Amish pedigree, Gerhard et al. (1984) observed an apparent crossover within the beta-globin gene cluster in the region of the recombinational 'hotspot' postulated by Chakravarti et al. (1984) on the basis of linkage disequilibrium in population data. It was also possible to identify the orientation of the beta-globin cluster vis-a-vis the centromere: cen--5-prime--epsilon--beta--3-prime--pter.

Camaschella et al. (1988) identified recombination between 2 paternal chromosomes in a region 5-prime to the beta gene, previously indicated to contain a 'hotspot' for recombination. The recombination was identified because in the course of prenatal diagnosis by linkage to RFLPs, a homozygous beta-thalassemia fetus was misdiagnosed as beta-thalassemia trait.

In the course of studying an Irish family with beta-thalassemia due to the Q39X mutation in the HBB gene (141900.0312), Hall et al. (1993) found a fourth case of recombination in the beta-globin gene cluster. The event had occurred 5-prime of the polymorphic RsaI site at position -550 bp upstream of the beta-globin gene mRNA cap site, within the 9.1-kb region shown to be a hotspot for recombination.

Huang et al. (1986) reported the same 'TATA' box mutation leading to the same nondeletion form of beta-thalassemia in Chinese as had been reported in American blacks by Antonarakis et al. (1984); see 141900.0379. There are other illustrations indicating that mutations in the beta-globin gene can recur.

Orkin et al. (1982) developed and applied a new strategy for the comprehensive analysis of existing mutations in a class of human disease. They combined analysis of various restriction enzyme polymorphisms in the beta-globin gene cluster with direct examination of beta-globin structural genes in Mediterranean persons with beta-thalassemia. The approach was prompted by the finding that specific mutant genes are strongly linked to patterns of restriction site polymorphism (haplotypes) in this region of the genome. They isolated 8 different mutant genes among the 9 different haplotypes represented in Mediterraneans. Seven of the 8 genes were present in Italians from various locales in Italy, and 6 in Greeks. Several were previously unknown mutations, and 1 of these possibly affects transcription. The strategy is probably applicable to the analysis of heterogeneity in other diseases of single-copy genes. When linkage analysis can be performed in the family, the haplotype analysis will be highly useful in prenatal diagnosis of beta-thalassemia. Indeed, the method of haplotyping proved highly useful both in tracing the origin of mutations and in family studies (see Antonarakis et al., 1982). Losekoot et al. (1992) described a method for rapid detection of beta-globin haplotypes (referred to by them as framework) by denaturing gradient gel electrophoresis.

Rosatelli et al. (1987) analyzed the molecular defect in 494 Sardinian beta-thalassemia heterozygotes. The most prevalent mutation, accounting for 95.4% of cases, was the nonsense mutation at codon 39 (141900.0312). The remainder, in decreasing order of frequency, were a frameshift at codon 6 (2.2%), beta-plus IVS1, nucleotide 110 (0.4%), and beta-plus IVS2, nucleotide 745 (0.4%). The DNA sequences along the human beta-globin cluster are highly polymorphic; over 20 polymorphic restriction endonuclease sites have been described in this 60-kb region. RFLP haplotypes have been useful in defining various thalassemia lesions, such as deletions, for prenatal diagnosis of beta-thalassemia, and for tracing the origin and migration of mutant genes.

Pirastu et al. (1987) found that the predominant beta-thalassemia in Sardinia, the beta-zero type due to nonsense mutation (CAG-to-TAG) at beta-39 (141900.0312), resides on 9 different chromosome haplotypes. One of the haplotypes included a cytosine-to-thymine point mutation 196 nucleotides upstream from the A-gamma-globin gene (142200.0027). The gamma-A mutation at position -196 is associated with high levels of production of fetal hemoglobin. The beta-39 nonsense mutation may have gotten onto the -196 chromosome through crossing-over. A chromosome carrying such a double mutation could be expected to impart selective advantage because the beta-thalassemia would protect against malaria while the increased gamma-globin production would ameliorate the severity of the beta-thalassemia. A similar mechanism may have been operative in the case of another haplotype which combined the beta-39 nonsense mutation with triple gamma loci produced by the addition of a second G-gamma-globin gene. Pirastu et al. (1987) proposed a schema by which the findings were explained by a single initial mutation with subsequent crossovers between the 5-prime and 3-prime blocks of genes producing 6 other chromosomes and then the creation of 2 others by crossing-over and gene conversion. Additional diversity could have arisen through other beta-39 mutations. The mutation identified in a family of northern European origin by Chehab et al. (1986) was of this type.

Direct sequencing of specific regions of genomic DNA became feasible with the invention of PCR, which permits amplification of specific regions of DNA (Church and Gilbert, 1984; Saiki et al., 1986). For example, Wong et al. (1986) amplified human mitochondrial DNA and sequenced it directly. Wong et al. (1987) applied a combination of PCR and direct sequence analysis of the amplified product to the study of beta-thalassemia in 5 patients whose mutant alleles had not been characterized. They found 2 previously undescribed mutations along with 3 previously known ones. One new allele was a frameshift at codons 106-107 and the other was an A-to-C transversion at the cap site (+1) of the beta-globin gene. The latter was the first natural mutation observed at the cap site (141900.0387).

In a study of beta-thalassemia in Spain, Amselem et al. (1988) demonstrated the usefulness of the dot-blot hybridization of PCR-amplified genomic DNA in both rapid population surveys and prenatal diagnosis. They found 7 different beta-thalassemia mutations. The nonsense codon 39 accounted for 64%, whereas the IVS1 position 110 mutation (141900.0364), the most common cause of beta-thalassemia in the eastern part of the Mediterranean basin, was underrepresented (8.5%). The IVS1 mutation at position 6 (141900.0360) accounted for 15% of the defects and led to a more severe form of beta(+)-thalassemia than originally described in most patients with this mutation.

Diaz-Chico et al. (1988) described 2 families, 1 Yugoslavian and 1 Canadian, with heterozygous thalassemia characterized by mild anemia with severe microcytosis and hypochromia, normal levels of hemoglobin A(2), and slightly raised hemoglobin F levels. In both families the condition resulted from large deletions which included all functional and pseudogenes of the beta-globin gene cluster. The deletion was at least 148 kb in the Yugoslavian family and 185 kb in the Canadian family.

Aulehla-Scholz et al. (1989) described a deletion comprising about 300 basepairs in a female heterozygote, resulting in loss of exon 1, part of IVS1, and the 5-prime beta-globin gene promoter region.

Laig et al. (1989) identified new beta-thalassemia mutations in northern and northeastern Thailand.

Rund et al. (1991) studied beta-thalassemia among Kurdistan Jews. They identified 13 distinct mutations among 42 sibships, of which 3 were previously undescribed. Four of the mutations (see 141900.0331, 141900.0341, 141900.0373, 141900.0383) were unique to Kurdish Jews and two-thirds of the mutant chromosomes carried the mutations unique to Kurdish Jews. Haplotype and geographic analyses suggested that thalassemia in central Kurdistan has evolved from multiple mutational events. Genetic admixture with the local population appears to be the primary mechanism of the evolution of thalassemia in Turkish Kurdistan, whereas there is evidence for a founder effect in Iranian Kurdistan.

Huang et al. (1990) used DNA from dried blood specimens amplified by PCR to study the distribution of beta-thalassemia mutations in southern, western, and eastern China.

As indicated by the work of Villegas et al. (1992), Oron et al. (1994), and Traeger-Synodinos et al. (1996), thalassemia intermedia is caused by interaction between a triplicated alpha-globin locus (leading to alpha-globin overproduction) and beta-thalassemia heterozygosity. Traeger-Synodinos et al. (1996) reported 3 cases of beta-thalassemia heterozygosity with homozygous alpha-globin gene triplication and 17 beta-thalassemia heterozygotes with a single additional alpha-globin gene. Garewal et al. (1994) likewise reported 2 patients with a clinical presentation of thalassemia intermedia due to homozygosity for alpha-gene triplication and heterozygosity for an HBB gene mutation.

Landin et al. (1996) noted that 34 of 316 beta-globin variants due to single amino acid substitutions could be caused by more than 1 type of point mutation at the DNA level. They also noted that 3 beta-globin variants (Hb Edmonton, Hb Bristol, and Hb Beckman) and 1 alpha-globin variant (Hb J-Kurosh) could not be produced by a single nucleotide substitution; 2 substitutions were required.

Several hemoglobin variants were first detected in the course of study of glycated hemoglobin (HbA1c) in diabetics, e.g., 141900.0429 and 141900.0477. The alternative situation, diagnosis of diabetes during the performance of hemoglobin electrophoresis for study of anemia, was observed by Millar et al. (2002).

Sierakowska et al. (1996) found that treatment of mammalian cells stably expressing the IVS2-654 beta HBB gene (141900.0348) with antisense oligonucleotides targeted at the aberrant splice sites restored correct splicing in a dose-dependent fashion, generating correct human beta-globin mRNA and polypeptide. Both products persisted for up to 72 hours after treatment. The oligonucleotides modified splicing by a true antisense mechanism without overt unspecific effects on cells growth and splicing of other pre-mRNAs. This novel approach in which antisense oligonucleotides are used to restore rather than to downregulate the activity of the target gene is applicable to other splicing mutants and is of potential clinical interest.

Erythrocytosis

Huisman et al. (1996) listed (in their Table 6B) 38 HBB variants causing erythrocytosis, plus 20 others causing mild erythrocytosis and 1 causing erythrocytosis in combination with hemolysis. (Some authors, Boyer et al. (1972), Charache et al. (1975), and Brennan et al. (1982), use polycythemia rather than erythrocytosis as the designation for the compensatory increase in red blood cell mass that accompanies hemoglobins with increased oxygen affinity. The 2 terms must be considered synonymous. Some, e.g., Hamilton et al. (1969), use erythremia. Although also a synonym of polycythemia and erythrocytosis, erythremia has become essentially obsolete.)

Hereditary Persistence of Fetal Hemoglobin

Part of the mutational repertoire of the beta-globin locus is hereditary persistence of fetal hemoglobin (HPFH; 141749) due to deletion. Two types (types I and II) occur in blacks and have as their basis deletion of the delta and beta loci. An Italian type and an Indian type are likewise deletion forms of HPFH; see review by Saglio et al. (1986). In 2 Italian brothers with a G-gamma/A-gamma form of hereditary persistence of fetal hemoglobin, Camaschella et al. (1990) demonstrated a deletion starting 3.2 kb upstream from the delta gene and ending within the enhancer region 3-prime to the beta-globin gene. The deletion removed 1 of the 4 binding sites for an erythroid specific transcriptional factor (NF-E1). It appeared that the residual enhancer element, relocated near gamma genes, may increase fetal hemoglobin expression.

Delta-Beta Thalassemia

In the so-called Corfu form of delta-beta-thalassemia, Kulozik et al. (1988) found that a deletion removed 7,201 basepairs containing part of the delta-globin gene and sequences upstream. The beta-globin gene contained a G-to-A mutation at position 5 in IVS1. The gamma-globin gene promoters were normal. In transfected HeLa cells, a normal message was produced from the mutated beta-globin gene at a level of approximately 20% of the normal, the remaining 80% being spliced at cryptic sites in exon 1 and intron 1. This indicated that the mutation in the beta-globin gene is not the sole cause of the complete absence of hemoglobin A in this form of thalassemia. Kulozik et al. (1988) concluded that the 7.2-kb deletion contains sequences necessary for the normal activation of the beta-globin gene. In the homozygous state there is complete absence of hemoglobin A and hemoglobin A(2) and a high level of hemoglobin F. Traeger-Synodinos et al. (1991) gave further data on the Corfu mutation.

Protection Against Malaria

Gouagna et al. (2010) used cross-sectional surveys of 3,739 human subjects and transmission experiments involving 60 children and over 6,000 mosquitoes in Burkina Faso, West Africa, to test whether the HBB variants HbC (141900.0038) and HbS (141900.0243), which are protective against malaria, are associated with transmission of the parasite from the human host to the Anopheles mosquito vector. They found that HbC and HbS were associated with significant 2-fold in vivo (p = 1.0 x 10(-6)) and 4-fold ex vivo (p = 7.0 x 10(-5)) increases of parasite transmission from host to vector. Gouagna et al. (2010) concluded that human genetic variation at the HBB locus can influence the efficiency of malaria transmission, possibly by promoting sexual differentiation of P. falciparum as a downstream phenotypic event. Alternatively, Gouagna et al. (2010) suggested that the higher infectivity of individuals with HBB variants in their study could be due to less frequent use of antimalarial drugs. In a commentary, Pasvol (2010) noted that little is known regarding the mechanisms involved in switching from the parasite asexual stages to the induction of gametogenesis, but that the hemoglobinopathies may provide a scenario beneficial to both host and parasite.

Reviews

Kazazian and Boehm (1988) gave an update on the variety of beta-thalassemias. Large deletions are a rare cause of beta-thalassemia; as of early 1989, 63 single nucleotide substitutions or small deletions and 7 large deletions had been described as the basis of beta-thalassemia (Kazazian, 1989).

Huisman (1990) provided a list of over 110 different beta-thalassemia alleles, most of them of the nondeletional type.

Huisman (1992) edited an up-to-date listing of the deletions, mutations, and frameshifts leading to beta-thalassemia, which had been published 3 times previously, and added a new table on the delta-thalassemias, prepared by Erol Baysal. Kazazian et al. (1992) tabulated a total of 9 beta-globin mutations producing dominant thalassemia-like phenotypes. Widespread ethnic derivation was demonstrated.

Krawczak et al. (1992) reviewed the mutational spectrum of single basepair substitutions in mRNA splice junctions on the basis of 101 different examples of point mutations occurring in the vicinity of splice junctions and held to be responsible for human genetic disease. The data comprised 62 mutations at 5-prime splice sites, 26 at 3-prime splice sites, and 13 that resulted in the creation of novel splice sites such as HbE. They estimated that up to 15% of all point mutations causing human genetic disease result in an mRNA splicing defect.

Carver and Kutlar (1995) listed 323 beta-chain variants as of January 1995. This number did not include beta-chain variants with deletions and/or insertions or those with extended polypeptide chains. Baysal and Carver (1995) provided an update (eighth edition) of their catalog, or repository, of beta-thalassemia and delta-thalassemia.

Huisman et al. (1996) provided a syllabus of human hemoglobin variants listing the characteristics as well as precise molecular change of known beta-globin mutants; these numbered 335 single-base mutations and 17 variants with 2 amino acid replacements as of January 1996. They also included hemoglobin variants resulting from fusion of parts of the beta-chain and delta-chain, variants with elongated beta-chains at both the C-terminal and N-terminal ends, and variants with small deletions and/or insertions in the beta-chain. Not included were deletions and mutations that result in beta-thalassemia, even if such a change, point mutation, or frameshift occurred in one of the coding regions of the HBB gene. Information regarding these abnormalities were provided elsewhere, e.g., Baysal and Carver (1995).

Huisman et al. (1996) stated that 138 of the 146 codons of the HBB gene have been mutated; 5 mutations are known for 6 codons (22, 67, 97, 121, 143, and 146), 6 mutations for codon 92, and 7 mutations for codon 99. Most of the mutations have been deduced from the sequence of the amino acid sequence of the variant protein and the known sequence of the HBB gene; slightly more than 10% of the mutations have been determined through DNA sequencing. Occasionally discrepancy was observed, such as at position 50 and 67 of the beta-globin chain.

Database of Hemoglobin Variants

Hardison et al. (2002) constructed a web-accessible relational database of hemoglobin variants and thalassemia mutations called HbVar, in which old and new data are incorporated. Queries can be formulated based on fields in the database. For example, tables of common categories of variants, such as all variants involving the HBA1 gene (141800) or all those that result in high oxygen affinity, can be assembled. More precise queries are possible, such as 'all beta-globin variants associated with instability and found in Scottish populations.'

Locus Control Region Beta

Cases of gamma-delta-beta thalassemia are known in which the beta gene is intact but deletion 'in cis' occurs upstream, even at a distance, in a region designated LCRB. In a remarkable case reported by Curtin et al. (1985), a deletion extended from the third exon of the G-gamma gene upstream for about 100 kb. The A-gamma, pseudo-beta, delta, and beta genes in cis were intact. This malfunction of the beta-globin gene on a chromosome in which the deletion is located 25 kb away suggests that chromatin structure and conformation are important for globin gene expression. In experiments in which the human beta-globin locus was introduced into the mouse genome, Talbot et al. (1989) found a 6.5-kb control region which allowed achievement of endogenous levels of beta-globin expression. The control region included an erythroid cell-specific DNase I hypersensitive site (HS). Using pulsed field gel electrophoresis and PCR, Driscoll et al. (1989) found, in a case of gamma-delta-beta-thalassemia, a de novo deletion on a maternally inherited chromosome 11 involving about 30 kb of sequences 5-prime to the epsilon gene. The deletion extended from -9.5 kb to -39 kb 5-prime of epsilon and included 3 of the 4 DNase I hypersensitive sites (at -10.9 kb, -14.7 kb, and -18 kb 5-prime of epsilon). The remaining sequences of the beta-globin complex, including the DNase I hypersensitive sites at -6.1 kb and all structural genes in cis to the deletion, were physically intact. Again, a significance of the hypersensitive sites in regulating globin-gene expression was demonstrated.

Epsilon-gamma-delta-beta-thalassemias are all caused by deletions of the beta-globin gene cluster on 11p. At the molecular level, the deletions fall into 2 categories: group I removes all or a greater part of the beta-globin cluster, including the beta-globin gene; group II removes extensive upstream regions leaving the beta-globin gene itself intact despite which its expression is silenced because of inactivation of the upstream beta-locus control region. A group I deletion was reported by Curtin et al. (1985). A group I deletion was reported in a Chilean family by Game et al. (2003), and an upstream deletion (group II) was reported in a Dutch family by Harteveld et al. (2003). Rooks et al. (2005) described 3 novel epsilon-gamma-delta-beta-thalassemia deletions in 3 English families, referred to as English II, III, and IV to distinguish them from the family of Curtin et al. (1985), which was also English (I). Two of the deletions removed the entire beta-globin gene complex, including a variable number of flanking olfactory receptor genes.

The significance of the hypersensitive sites to globin gene expression had also been demonstrated by Grosveld et al. (1987) who achieved high levels of position-independent beta-gene expression in transgenic mice with a specially constructed beta-globin minilocus in which 5-prime and 3-prime hypersensitive sequences flanked a beta-globin gene. The hypersensitive sequences, termed locus-activating regions (LARs), are erythroid-tissue-specific and developmentally stable. Curtin et al. (1989) performed experiments similar to those of Grosveld et al. (1987) with like results. (A similar positive control region for the cluster of alpha-globin genes was deduced by Hatton et al. (1990) on the basis of deletion in a case of alpha-thalassemia; see 141800.) See 187550 for evidence of an unlinked remote regulator of HBB gene expression. Townes and Behringer (1990) reviewed the topic of the locus activating region. They presented a model for developmental control of human globin gene expression (see their Figure 2). With respect to the cap site of the human epsilon-globin gene, LAR site I is located at position -6.1 kb; site II, at -10.9 kb; site III, at -14.7 kb; and site IV, at -18 kb. Moon and Ley (1990) cloned murine DNA sequences homologous to the human LAR site II. These sequences are linked to the mouse beta-globin gene cluster in the same basic arrangement as the human beta-globin gene cluster. Furthermore, the 2 LARs share 70% identical sequence and several enhancer-type functions. LAR sequences are almost certainly not confined to the human beta-globin locus. The investigators stated that these sequences may be critical components of any gene family that comprises multiple members that are regulated differently during development.

Perichon et al. (1993) demonstrated interethnic polymorphism of 1 segment of the LCRB region in sickle cell anemia patients. Distinct polymorphic patterns of a simple sequence repeat were observed in strong linkage disequilibrium with each of the 5 major beta-S haplotypes.

Studies by Grosveld et al. (1987) and by Blom van Assendelft et al. (1989) established that 6 DNase I hypersensitive sites flank the globin genes. One HS site is located 20 kb downstream of the beta-globin cluster and 5 HS sites are located 6-22 kb upstream within the locus control region (LCR). Peterson et al. (1996) examined the effects of deletion of the LCR 5-prime HS3 element and the 5-prime HS2 element on globin gene expression by recombining a 2.3-kb deletion of 5-prime HS3 or a 1.9-kb deletion of 5-prime HS2 into a beta-globin locus YAC, which was then used to produce transgenic mice. When the LCR 5-prime HS3 element is deleted there is decreased expression of epsilon-globin in the yolk sac. Deletion of 5-prime HS2 resulted in a minor but statistically significant decrease in epsilon-, gamma-, and beta-globin expression. From these results Peterson et al. (1996) concluded that there is functional redundancy among the HS sites. The effects of the 5-prime HS3 deletion on epsilon-globin gene expression led them to conclude that specific interactions between the HSs and the globin genes underlie activation of globin genes during specific stages of development.

Epner et al. (1998) deleted the murine beta-globin LCR from its native chromosomal location. The approximately 25-kb deletion eliminated all sequences and structures homologous to those defined as the human LCR. In differentiated embryonic stem cells and erythroleukemia cells containing the LCR-deleted chromosome, DNase I sensitivity of the beta-globin domain was established and maintained, developmental regulation of the locus was intact, and beta-like globin RNA levels were reduced 5 to 25% of normal. Thus, in the native murine beta-globin locus, the LCR was necessary for normal levels of transcription, but other elements were sufficient to establish the open chromatin structure, transcription, and developmental specificity of the locus. These findings suggest a contributory rather than dominant function for the LCR in its native location.

Bauchwitz and Costantini (2000) quantified the effects of beta-globin sequence modifications on epsilon-, gamma-, and delta-globin levels in transgenic mice. Embryonic day 11.5 primitive erythroid cells showed a large increase in epsilon-globin in the absence of the beta-globin gene, which is weakly expressed at that stage of development. Embryonic day 17.5 fetal liver and adult erythroid cells, in which beta-globin expression approaches its maximum, showed only a small stimulation of gamma- and delta-globin levels in the absence of beta-globin sequence. Analysis of erythroid colonies produced by in vitro differentiation of embryonic stem cells indicated that the absence of the human beta-globin gene had no effect on gamma-globin expression. The authors concluded that competitive influences need not be linked directly to transcriptional level or distance from the LCR, and that the large increases in gamma-globin levels seen in some human deletional beta-thalassemias and hereditary persistence of fetal hemoglobin conditions are most likely due to effects other than loss of beta-globin competition. In transgenic mice with beta-globin sequences inserted between epsilon and the LCR in a beta-locus, the expression of epsilon-, gamma-, and delta-globins suggested that stage-specific sensitivity to loss of LCR activity may be a more important parameter than position relative to the LCR.

Alami et al. (2000) created a yeast artificial chromosome containing an unmodified human beta-globin locus, and introduced it into transgenic mice at various locations in the genome. The locus was not subject to detectable stable position effects but did undergo mild-to-severe variegating position effects at 3 of the 4 noncentromeric integration sites tested. The distance and the orientation of the LCR relative to the regulated gene contributed to the likelihood of variegating position effects, and affected the magnitude of its transcriptional enhancement. DNaseI hypersensitive site (HSS) formation varied with the proportion of expressing cells (variegation), rather than the level of gene expression, suggesting that silencing of the transgene may be associated with a lack of HSS formation in the LCR region. The authors concluded that transcriptional enhancement and variegating position effects are caused by fundamentally different but interdependent mechanisms.

Navas et al. (2002) generated transgenic mouse lines carrying a beta-globin locus YAC lacking the LCR to determine if the LCR is required for globin gene activation. Beta-globin gene expression was analyzed by RNase protection, but no detectable levels of epsilon-, gamma-, and beta-globin gene transcripts were produced at any stage of development. Lack of gamma-globin gene expression was also seen in a beta-YAC transgenic mouse carrying a gamma-globin promoter mutant that causes hereditary persistence of fetal hemoglobin (see 142200.0026) and an HS3 core deletion that specifically abolishes gamma-globin gene expression during definitive erythropoiesis. The authors concluded that the presence of the LCR is a minimum requirement for globin gene expression.

Navas et al. (2003) assessed the contribution of the GT6 motif within HS3 of the LCR on downstream globin gene expression by mutating GT6 in a beta-globin locus YAC and measuring the activity of beta-globin genes in GT6-mutated beta-YAC transgenic mice. They found reduced expression of epsilon- and gamma-globin genes during embryonic erythropoiesis. During definitive erythropoiesis, gamma-globin gene expression was significantly reduced while beta-globin gene expression was virtually indistinguishable from that of wildtype controls. Navas et al. (2003) concluded that the GT6 motif is required for normal epsilon- and gamma-globin gene expression during embryonic erythropoiesis and for gamma-globin gene expression during definitive erythropoiesis in the fetal liver.

Bottardi et al. (2005) noted that abnormal epigenetic regulation of gene expression contributes significantly to a variety of human pathologies including cancer. Deletion of HS2 at the human beta-globin locus control region can lead to abnormal epigenetic regulation of globin genes in transgenic mice. The authors used 2 HS2-deleted transgenic mouse lines as a model to demonstrate that heritable alteration of chromatin organization at the human beta-globin locus in multipotent hematopoietic progenitors can contribute to the abnormal expression of the beta-globin gene in mature erythroid cells. This alteration was characterized by specific patterns of histone covalent modifications that were inherited during erythropoiesis and, moreover, was plastic because it could be reverted by transient treatment with a histone deacetylase inhibitor. Bottardi et al. (2005) concluded that aberrant epigenetic regulation can be detected and modified before tissue-specific gene transcription.

Note Regarding the Allelic Variants Section

In the allelic variants listed below, as well as in the allelic variants listed under the other globin genes, the codon count begins with the first amino acid of the mature protein because a large portion of the variants were characterized on the basis of a protein rather than the gene itself. It is more customary for the count to begin with the methionine initiator codon as number one. Thus, the HbS mutation (141900.0243) is designated glu6-to-val; in the gene based system of counting now used, it would be designated glu7-to-val. Some inconsistency is represented by the fact that some initiator mutations in the globin genes are indicated by a system counting from the initiator methionine; e.g., beta-thalassemia due to met1-to-ile (141900.0430).


Animal Model

Ciavatta et al. (1995) created a mouse model of beta-zero-thalassemia by targeted deletion of both adult beta-like globin genes, beta(maj) and beta(min), in mouse embryonic stem cells. Heterozygous animals derived from the targeted cells were severely anemic with dramatically reduced hemoglobin levels, abnormal red cell morphology, splenomegaly, and markedly increased reticulocyte counts. Homozygous animals died in utero; however, heterozygous mice were fertile and transmitted the deleted allele to progeny. The anemic phenotype was completely rescued in progeny derived from mating beta-zero-thalassemic animals with transgenic mice expressing high levels of human hemoglobin A. The authors suggested that beta-zero-thalassemic mice could be used to test genetic therapy for beta-zero-thalassemia and could be bred with transgenic mice expressing high levels of hemoglobin S to produce an improved mouse model of sickle cell disease.

Hemoglobin disorders were among the first to be considered for gene therapy. Transcriptional silencing of genes transferred into hematopoietic stem cells, however, posed one of the most significant challenges to its success. If the transferred gene is not completely silenced, a progressive decline in gene expression as mice age often is encountered. These phenomena were observed to various degrees in mouse transplant experiments using retroviral vectors containing a human beta-globin gene, even when cis-linked to locus control region derivatives. Kalberer et al. (2000) investigated whether ex vivo preselection of retrovirally transduced stem cells on the basis of expression of the green fluorescent protein driven by the CpG island phosphoglycerate kinase (311800) promoter could ensure subsequent long-term expression of a cis-linked beta-globin gene in the erythroid lineage of transplanted mice. They observed that 100% of 7 mice engrafted with preselected cells concurrently expressed human beta-globin and green fluorescent protein in 20 to 95% of their red blood cells for up to 9.5 months posttransplantation, the longest time point assessed. This expression pattern was successfully transferred to secondary transplant recipients. In the presence of the beta-locus control region hypersensitivity site 2 alone, human beta-globin mRNA expression levels ranged from 0.15 to 20% with human beta-globin chains detected by HPLC. Neither the proportion of positive blood cells nor the average expression levels declined with time in translated recipients.

Persons and Nienhuis (2000) discussed the background of the work by Kalberer et al. (2000), including position effect variegation (PEV). Both PEV and silencing mechanisms may act on a transferred globin gene residing in chromatin outside of the normal globin locus during the important terminal phases of erythroblast development when globin transcripts normally accumulate rapidly despite heterochromatization and shutdown of the rest of the genome.


History

By autoradiography using heavy-labeled hemoglobin-specific messenger RNA, Price et al. (1972) found labeling of a chromosome 2 and a group B chromosome. They concluded, incorrectly as it turned out, that the beta-gamma-delta linkage group was on a group B chromosome since the zone of labeling was longer on that chromosome than on chromosome 2 (which by this reasoning was presumed to carry the alpha locus or loci). Study of a case of the Wolf-Hirschhorn syndrome (4p-) suggested that the B group chromosome involved is chromosome 4. Barbosa et al. (1975) excluded a recombination fraction of less than 0.30 for MN and Hb-beta.

McCurdy et al. (1975) thought the beta locus in some persons might be duplicated; they observed a black woman who had hemoglobin A and 2 different variant hemoglobins, each with a beta-globin change. One of these, however, proved to be a posttranslational change (Charache et al., 1977). El-Hazmi et al. (1986) suggested that the presence of 2 beta-globin genes might account for the finding of triple HpaI fragments in a case of sickle cell anemia. They explained its origin by unequal crossing-over.

Housman et al. (1979) used a panel of hybrid hamster-human cells deleted by x-ray and selected by a double antibody technique (the method of Kao, Jones, and Puck) to assign the NAG cluster to 11p12, between LDHA distally and ACP2 proximally. The orientation of the cluster in relation to the centromere was not known.

Although some workers have put the insulin (176730), beta-globin, and HRAS (190020) genes on 11p15, Chaganti et al. (1985) located these differently by in situ hybridization to meiotic chromosomes: INS, 11p14.1; HRAS, 11p14.1; HBB, 11p11.22; and PTH (not previously assigned), 11p11.21.


ALLELIC VARIANTS ( 541 Selected Examples):

.0001 HEMOGLOBIN AALBORG

HBB, GLY74ARG
  
RCV000016242

.0002 HEMOGLOBIN ABRUZZO

HBB, HIS143ARG
  
RCV000016243...

.0003 HEMOGLOBIN AGENOGI

HBB, GLU90LYS
  
RCV000016244...

See Miyaji et al. (1966). As indicated by Corso et al. (1990), carriers of the mutation had been found in only 3 families, an American black, a Sicilian, and a Hungarian family, suggesting independent origins of the mutation. Corso et al. (1990) described another Sicilian family in which 5 members carried Hb Agenogi; in 1, it was associated with beta-zero-thalassemia. The proposita, a 40-year-old woman with 2 children, came to attention because of mild chronic anemia and biliary colic due to gallstones.

Noguera et al. (2002) described Hb Agenogi in an Argentinian patient with Syrian and Hungarian ancestry. The mutation had previously been described in only 5 families, one of which was from Hungary.


.0004 HEMOGLOBIN ALABAMA

HBB, GLN39LYS
  
RCV001811595...

.0005 HEMOGLOBIN ALAMO

HBB, ASN19ASP
  
RCV000016246

.0006 HEMOGLOBIN ALBERTA

ERYTHROCYTOSIS 6, INCLUDED
HBB, GLU101GLY
  
RCV000016247...

.0007 HEMOGLOBIN ALTDORF

HBB, ALA135PRO
  
RCV000016248

.0008 HEMOGLOBIN ANDREW-MINNEAPOLIS

ERYTHROCYTOSIS 6, INCLUDED
HBB, LYS144ASN
  
RCV000016249...

See Zak et al. (1974). Hebbel et al. (1978) used this hemoglobin to make ingenious observations on adaptation of humans to high altitudes.


.0009 HEMOGLOBIN ANKARA

HBB, ALA10ASP
  
RCV000016250

.0010 HEMOGLOBIN ARLINGTON PARK

HBB, GLU6LYS AND LYS95GLU
  
RCV000016251...

May have arisen either through a second mutation in a person with HbC or Hb N(Baltimore), or through crossing-over in a person who was heterozygous for both mutant hemoglobins. See Adams and Heller (1977).


.0011 HEMOGLOBIN ATHENS-GEORGIA

HEMOGLOBIN WACO
HBB, ARG40LYS
  
RCV000016252...

.0012 HEMOGLOBIN ATLANTA

HBB, LEU75PRO
  
RCV000016254...

Unstable hemoglobin. See Hubbard et al. (1975) and Brennan et al. (1983).


.0013 HEMOGLOBIN ATLANTA-COVENTRY

HBB, LEU75PRO AND LEU141DEL
  
RCV000016254...

Brennan et al. (1986) described a 25-year-old man with congenital hemolytic anemia who was found to have the mutation of Hb Atlanta (beta75 leu-to-pro) and that of Hb Coventry (beta141 leu deleted) in the same beta-globin chain along with a normal beta-globin chain and a beta-globin chain with only the Hb Atlanta mutation. They stated that this is the sixth known example of 2 changes in 1 beta chain. They postulated that the doubly abnormal beta-globin was a beta-delta globin originating by a Lepore-type-mechanism. Brennan et al. (1992) found on restudy that leu141 was in fact not deleted but replaced by a novel amino acid which they suggested was hydroxyleucine; they proposed that the change resulted from posttranslational oxidation of leu141 as a consequence of perturbation of the haem environment caused by the leu75-to-pro mutation. The finding was consistent with the report of George et al. (1992) who found no evidence of deletion of leu141 in genomic DNA. The heterozygous patients have 3 hemoglobins: HbA, Hb Atlanta, and Hb Atlanta-Coventry. The last 2 are the products of a single gene. A similar situation obtains with Hb Vicksburg (141900.0293), in which deletion of leu75 is not coded for in genomic DNA. Coleman et al. (1988) posited somatic mutation in that instance; however, a mechanism similar to that with Hb Atlanta-Coventry is possible.


.0014 HEMOGLOBIN AUSTIN

HBB, ARG40SER
  
RCV000016256

.0015 HEMOGLOBIN AVICENNA

HBB, ASP47ALA
  
RCV000016257

.0016 HEMOGLOBIN BARCELONA

ERYTHROCYTOSIS 6, INCLUDED
HBB, ASP94HIS
  
RCV000016258...

See Wajcman et al. (1982). This is a high oxygen affinity hemoglobin variant.


.0017 HEMOGLOBIN BAYLOR

HBB, LEU81ARG
  
RCV000016259

.0018 HEMOGLOBIN BEIRUT

HBB, VAL126ALA
  
RCV000016260...

.0019 HEMOGLOBIN BELFAST

HBB, TRP15ARG
  
RCV000016261

See Kennedy et al. (1974).

Galanello et al. (2004) reported the sixth occurrence of Hb Belfast, a change of codon 15 of the HBB gene from TGG (trp) to AGG (arg) (trp15 to arg; W15R), in a large Italian family with 9 affected members. The oxygen affinity of the isolated variant was increased. The clinical phenotype was silent or very mild, the only clinical finding being an intermittent moderate jaundice.


.0020 HEMOGLOBIN BEOGRAD

HEMOGLOBIN D (CAMPERDOWN)
HBB, GLU121VAL
  
RCV000016264...

See Efremov et al. (1973), Wilkinson et al. (1975), and Ruvidic et al. (1975).

Akar et al. (1995) described a dual restriction enzyme digestion protocol for discriminating between Hb Beograd and Hb D (Los Angeles) (glu121 to gln) when they occur in the same population. Both of these variants migrate like HbS on cellulose acetate electrophoresis. Hb O (Arab) (glu121 to lys; 141900.0202) represents no problem because that variant migrates differently on cellulose acetate electrophoresis. Also, the glu121-to-ter mutation (141900.0314) represents no problem because it is associated with a thalassemia phenotype. Other codon 121 mutations are Hb D (Neath) (glu121 to-ala; 141900.0445) and Hb St. Francis (glu121 to gly; 141900.0412).


.0021 HEMOGLOBIN BETH ISRAEL

HBB, ASN102SER
  
RCV000016266

Like Hb Kansas, this variant was associated with clinically evident cyanosis due to very low oxygen affinity (Nagel et al., 1976). (The hemoglobins M are not the only anomalous hemoglobins associated with cyanosis.)


.0022 HEMOGLOBIN BETHESDA

ERYTHROCYTOSIS 6, INCLUDED
HBB, TYR145HIS
  
RCV000016267...

.0023 HEMOGLOBIN BICETRE

HBB, HIS63PRO
  
RCV000016268

.0024 HEMOGLOBIN BOLOGNA

HBB, LYS61MET
  
RCV000016269

.0025 HEMOGLOBIN BORAS

HBB, LEU88ARG
  
RCV000016262

.0026 HEMOGLOBIN BOUGARDIREY-MALI

HBB, GLY119VAL
  
RCV000016263

.0027 HEMOGLOBIN BREST

HBB, GLN127LYS
  
RCV000016270

.0028 HEMOGLOBIN BRIGHAM

ERYTHROCYTOSIS 6, INCLUDED
HBB, PRO100LEU
  
RCV000016271...

This variant is a cause of erythrocytosis. See Lokich et al. (1973).


.0029 HEMOGLOBIN BRISBANE

HEMOGLOBIN GREAT LAKES
ERYTHROCYTOSIS 6, INCLUDED
HBB, LEU68HIS
  
RCV000016272...

.0030 HEMOGLOBIN BRISTOL

HBB, VAL67MET-TO-ASP
  
RCV000016276...

See Steadman et al. (1970) and Ohba et al. (1985).

Rees et al. (1996) reinvestigated the patient who was the subject of the first description of idiopathic Heinz body anemia (140700) (Cathie, 1952) and who was subsequently shown to have hemoglobin Bristol. Using both DNA and protein analysis, they showed that the original characterization of hemoglobin Bristol as val67 to asp was incorrect, in that a silent posttranslational modification of met to asp was mistaken for the primary mutation, which is, in fact, val67 to met. They also restudied 2 subsequent patients reported as having hemoglobin Bristol following protein sequencing in whom the same confusion occurred. They were able to describe a novel posttranslational modification in which the variant methionine amino acid residue is converted to an aspartate, probably catalyzed by the neighboring heme group and oxygen. The study emphasized the importance of analyzing both protein and DNA to characterize fully hemoglobin variants. Identification of the lesion as val67 to asp was made by Steadman et al. (1970).

Although DNA codes for 20 primary amino acids, more than 140 different residues have been identified in proteins due to varied posttranslational modifications. Most are relatively simple reactions involving enzymatic modification of the site change of amino acids to enhance or determine the properties of the particular protein; these processes include acetylation, phosphorylation, hydroxylation, and glycation. There are also a number of posttranslational modifications of hemoglobin A, such as glycation and carbamoylation, but these are due mostly to nonspecific metabolic affects that alter the chemical environment of the hemoglobin, rather than direct results of the properties of the hemoglobin itself. Unstable hemoglobin variants are characterized by the reduced solubility of the hemoglobin tetramer in the red cell in peripheral blood. Most result from mutations of amino acids in key positions, for example, heme- or alpha-beta contact points. Mutations can also alter the structure of the molecule such that posttranslational changes can occur, either of the variant amino acid itself or of other residues exposed by changes in the conformation of the molecule. More rarely, so-called silent modifications occur, in which 1 primary amino acid is converted to another primary amino acid. This is what happened in the case of hemoglobin Bristol. The modification of beta-143 leu, such that it appears to be deleted on protein sequencing, in hemoglobin Atlanta-Coventry (141900.0013) is the result of posttranslational modification, possibly from leucine to hydroxyleucine, as a result of the primary mutation that effects the heme surface. The same apparent deletion of leu-149 is observed with Hb Christchurch (141900.0049) and with Hb Manukau (141900.0438), which is also a mutation of val67 (val67 to gly). There are 6 reported hemoglobin variants in which deamidation of an asparaginyl residue to an aspartate occurs as a silent posttranslational modification: these include hemoglobin Osler (141900.0211). The posttranslational change from methionine to aspartate was the first example to be described (Rees et al., 1996); the exact mechanism of the change is not clear.


.0031 HEMOGLOBIN BRITISH COLUMBIA

ERYTHROCYTOSIS 6, INCLUDED
HBB, GLU101LYS
  
RCV000016274...

.0032 HEMOGLOBIN BROCKTON

HBB, ALA138PRO
  
RCV000016275

See Moo-Penn et al. (1980, 1988) and Ulukutlu et al. (1989). Negri Arjona et al. (1992) found a GCT (ala)-to-CCT (pro) mutation in codon 138 in a 6-year-old Spanish girl with chronic hemolytic anemia requiring transfusion. The patient showed Heinz bodies. Her parents and a brother were normal, indicating that her disorder represented a new mutation.

Tsoi et al. (1998) identified Hb Brockton in a 9-year-old Chinese boy with long-standing hemolysis. As in previous reports, the mutation occurred de novo. Tsoi et al. (1998) noted that the patient also had moyamoya disease (see 252350).


.0033 HEMOGLOBIN BRUXELLES

HEINZ BODY HEMOLYTIC ANEMIA
HBB, PHE41DEL OR PHE42DEL
  
RCV000016277...

Blouquit et al. (1989) demonstrated that hemoglobin Bruxelles, a beta-globin variant associated with severe congenital Heinz body anemia, has a deletion of 1 of the 2 adjacent phenylalanines, either phe41 or phe42. Other deletions affecting the phe41 or phe42 have been described. The nucleotide sequence of normal beta-globin mRNA is highly repetitive in the region of codons 41 to 46. Blouquit et al. (1989) suggested that the mutation originated through a frameshift mechanism.


.0034 HEMOGLOBIN BRYN MAWR

HEMOGLOBIN BUENOS AIRES
HBB, PHE85SER
  
RCV000016279...

.0035 HEMOGLOBIN BUNBURY

HBB, ASP94ASN
  
RCV000016281...

See Como et al. (1983). This is a high oxygen affinity hemoglobin variant.


.0036 HEMOGLOBIN BURKE

HBB, GLY107ARG
  
RCV000016282

.0037 HEMOGLOBIN BUSHWICK

HBB, GLY74VAL
  
RCV000016283

.0038 HEMOGLOBIN C

MALARIA, RESISTANCE TO, INCLUDED
HBB, GLU6LYS
  
RCV000016251...

See Itano and Neel (1950), Neel et al. (1953), Ranney et al. (1953), Hunt and Ingram (1959), Smith and Krevans (1959), Baglioni and Ingram (1961), River et al. (1961), and Fabry et al. (1981).

By restriction haplotyping, Boehm et al. (1985) concluded that the beta-C-globin gene in blacks had a single origin followed by spread of the mutation to other haplotypes through meiotic recombination 5-prime to the beta-globin gene. On 22 of 25 chromosomes studied, they found the same haplotype (defined by 8 polymorphic restriction sites), a haplotype seen only rarely among beta-A-bearing chromosomes. The 3 exceptions showed identity to the typical beta-C allele in the 3-prime end of the beta-globin gene cluster. Trabuchet et al. (1991) presented haplotyping information suggesting a unicentric origin of the HbC mutation in sub-Saharan Africa.

Rapid detection of the sickle cell mutation is possible by amplifying the region of codon 6 by PCR and digesting the amplification product by a restriction endonuclease whose recognition site is abolished by the A-to-T mutation, the resulting abnormal fragment being detected with ethidium bromide staining after electrophoresis. Detection of the HbC mutation is more difficult since no known restriction-endonuclease site is abolished or created by the mutation. Fischel-Ghodsian et al. (1990) described a rapid allele-specific PCR amplification technique that allowed detection of the HbC mutation in an even shorter time span than the one required for detecting the HbS mutation (141900.0243).

To test the hypothesis that hemoglobin C protects against severe malaria (611162), Agarwal et al. (2000) conducted a study in the predominantly Dogon population of Bandiagara, Mali, in West Africa, where the frequency of HbC is high (0.087) and that of HbS is low (0.016). They found evidence for an association between HbC and protection against severe malaria in the Dogon population. Indeed, the data suggested less selection for the HbAS state in this group than for HbAC.

In many children with sickle cell disease (603903), functional asplenia develops during the first year of life and septicemia is the leading cause of death in childhood. The risk of septicemia in sickle cell anemia is greatest during the first 3 years of life and is reduced markedly by prophylactic penicillin therapy. Less is known about splenic dysfunction and the risk of overwhelming sepsis in children with SC disease, although functional asplenia has been documented by radionuclide liver-spleen scans in some adult patients (Ballas et al., 1982) and an elevated erythrocyte pit count, a finding that indicates functional asplenia in children with sickle cell anemia, also has been found in some children with SC disease (Pearson et al., 1985). Lane et al. (1994) reported 7 fatal cases of pneumococcal septicemia in children with SC disease. The earliest death occurred in a 1-year-old child who had cyanotic congenital heart; the other children were aged 3.5 to 15 years. Only 1 child had received pneumococcal vaccine or prophylactic penicillin therapy. All 7 children had an acute febrile illness and rapid deterioration despite parenterally administered antibiotic therapy and intensive medical support. Erythrocyte pit counts in 2 patients were 40.3 and 41.7%, respectively (normal, less than 3.6%). Autopsy findings in 5 cases included splenic congestion without infarction in 5, splenomegaly in 4, and bilateral adrenal hemorrhage in 3. Lane et al. (1994) concluded that pneumococcal vaccine should be administered in all children with SC disease. The routine use of prophylactic penicillin therapy in infants and children with SC disease remained controversial. The mutation in codon 6 of HBB in HbS is GAG (glu) to GTG (val); the mutation in HbC is GAG (glu) to AAG (lys). See also 141900.0039 and 141900.0040.

Modiano et al. (2001) performed a large case-control study in Burkina Faso on 4,348 Mossi subjects, and demonstrated that hemoglobin C is associated with a 29% reduction in risk of clinical malaria in HbAC heterozygotes (P = 0.0008) and of 93% in HbCC homozygotes (P = 0.0011). These findings, together with the limited pathology of HbAC and HbCC compared to the severely disadvantaged HbSS and HbSC genotypes and the low HbS gene frequency in the geographic epicenter of HbC, support the hypothesis that, in the long-term and in the absence of malarial control, HbC would replace HbS in central West Africa.

Rihet et al. (2004) surveyed 256 individuals (71 parents and 185 sibs) from 53 families in Burkina Faso over 2 years and found that hemoglobin C carriers were found to have less frequent malaria attacks than AA individuals within the same age group (P = 0.01). Analysis of individual hemoglobin alleles yielded a negative association between HbC and malaria attack (P = 0.00013). Analyses that took into account confounding factors confirmed the negative association of HbC with malaria attack (P = 0.0074) and evidenced a negative correlation between HbC and parasitemia (P = 0.0009).

Fairhurst et al. (2005) reported a marked effect of hemoglobin C on the cell-surface properties of P. falciparum-infected erythrocytes involved in pathogenesis. Relative to parasite-infected normal erythrocytes (HbAA), parasitized AC and CC erythrocytes showed reduced adhesion to endothelial monolayers expressing CD36 (173510) and intercellular adhesion molecule-1 (ICAM1; 147840). They also showed impaired rosetting interactions with nonparasitized erythrocytes, and reduced agglutination in the presence of pooled sera from malaria-immune adults. Abnormal cell-surface display of the main variable cytoadherence ligand, PfEMP-1 (P. falciparum erythrocyte membrane protein-1), correlated with these findings. The abnormalities in PfEMP-1 display were associated with markers of erythrocyte senescence, and were greater in CC than in AC erythrocytes. Fairhurst et al. (2005) suggested that hemoglobin C might protect against malaria by reducing PfEMP1-mediated adherence of parasitized erythrocytes, thereby mitigating the effects of their sequestration in the microvasculature.

Recombinational hotspots are a ubiquitous feature of the human genome, occurring every 60 to 200 kb, and likely contribute to the observed pattern of large haplotypic blocks punctuated by low linkage disequilibrium (LD) over very short (1 to 2 kb) distances. Recombination breaks up ancestral LD and produces new combinations of alleles on which natural selection can act. Positive selection increases the frequency of beneficial mutations, creating LD via genetic 'hitchhiking.' The beta-globin hotspot spans approximately 1 kb and is located approximately 500 bp from the selected site at the beta-globin gene. The close proximity of these beta-globin regions allowed Wood et al. (2005) to empirically examine the signature of selection across a region that recombines at a rate 50 to 90 times higher than the genomic average of 1.1 cM/Mb. Early studies of the HbC polymorphism suggested that this allele was, like the hemoglobin S allele (141900.0243), also subject to balancing selection (Allison, 1954). Subsequently, it was shown that HbC provides protection against Plasmodium falciparum without significantly reducing fitness, indicating that this allele is increasing in frequency as a result of positive directional selection (Agarwal et al., 2000; Modiano et al., 2001; Hedrick, 2004; Rihet et al., 2004). Because the African HbC allele rarely exceeds frequencies of 20% and is geographically concentrated in central West Africa, it is thought that this mutation is very young. Wood et al. (2005) examined the extent of LD surrounding the African HbC allele to estimate its age and the strength of selection acting on this mutation and tested the hypothesis that the beta-globin recombinational hotspot decouples the selected HbC allele from nearby upstream regions. They estimated that the HbC mutation originated less than 5,000 years ago and that selection coefficients are between 0.04 and 0.09. Despite strong selection and the recent origin of the HbC allele, recombination (crossing-over or gene conversion) is observed within 1 kb 5-prime of the selected site on more than one-third of the Hb chromosomes sampled. The rapid decay in LD upstream of the HbC allele demonstrates the large effect the beta-globin hotspot has in mitigating the effects of positive selection on linked variation, in other words a reduction in 'hitchhiking.'

Modiano et al. (2008) adopted 2 partially independent haplotypic approaches to study the Mossi population in Burkina Faso, where both the HbS and HbC alleles are common. They showed that both alleles are monophyletic, but that the HbC allele has acquired higher recombinatorial and DNA slippage haplotypic variability or linkage disequilibrium decay and is likely older than HbS. Modiano et al. (2008) inferred that the HbC allele has accumulated mainly through recessive rather than a semidominant mechanism of selection.

Gouagna et al. (2010) used cross-sectional surveys of 3,739 human subjects and transmission experiments involving 60 children and over 6,000 mosquitoes in Burkina Faso, West Africa, to test whether the HBB variants HbC and HbS, which are protective against malaria, are associated with transmission of the parasite from the human host to the Anopheles mosquito vector. They found that HbC and HbS were associated with significant 2-fold in vivo (P = 1.0 x 10(-6)) and 4-fold ex vivo (P = 7.0 x 10(-5)) increases of parasite transmission from host to vector. In addition, the HbC allele was consistently associated with higher gametocyte rate.

Cyrklaff et al. (2011) found that HbS (141900.0243) and HbC affect the trafficking system that directs parasite-encoded proteins to the surface of infected erythrocytes. Cryoelectron tomography revealed that P. falciparum generates a host-derived actin cytoskeleton within the cytoplasm of wildtype red blood cells that connects the Maurer clefts with the host cell membrane and to which transport vesicles are attached. The actin cytoskeleton and the Maurer clefts were aberrant in erythrocytes containing HbS or HbC. Hemoglobin oxidation products, enriched in HbS and HbC erythrocytes, inhibited actin polymerization in vitro and may account for the protective role in malaria.


.0039 HEMOGLOBIN C (GEORGETOWN)

HEMOGLOBIN C (HARLEM)
HBB, GLU6VAL AND ASP73ASN
  
RCV000016286...

Red cells containing this hemoglobin, with 2 mutations in the HBB gene, sickle. The sickling is the result, of course, of the glu-to-val mutation, which is not counteracted by the asp73-to-asn mutation. It is called HbC (not S) because of its electrophoretic properties. See Pierce et al. (1963), Bookchin et al. (1966, 1968, 1970), and Lang et al. (1972).


.0040 HEMOGLOBIN C (ZIGUINCHOR)

HEMOGLOBIN ZIGUINCHOR
HBB, GLU6VAL AND PRO58ARG
  
RCV000016286...

As in the other cases of doubly substituted beta chains, either double mutation or intracistronic recombination in a genetic compound would explain the observation. This hemoglobin sickles because of its glu6-to-val substitution, but is called HbC (not S) because of its electrophoretic properties, which are those of classic HbC. See Goossens et al. (1975) and Hassan et al. (1977).


.0041 HEMOGLOBIN CAMDEN

HEMOGLOBIN MOTOWN
HEMOGLOBIN TOKUCHI
HBB, GLN131GLU
  
RCV000507699...

See Wade Cohen et al. (1973) and Honig et al. (1980). Hmoglobin Motown was formerly thought to be a change at beta 127 (Gibb, 1981). See Ohba et al. (1975); hemoglobin Tokuchi was formerly thought to be a substitution of tyrosine for histidine at beta 2 (Shibata et al., 1963).


.0042 HEMOGLOBIN CAMPERDOWN

HBB, ARG104SER
  
RCV000016293...

.0043 HEMOGLOBIN CARIBBEAN

HBB, LEU91ARG
  
RCV000016294...

.0044 HEMOGLOBIN CASTILLA

HBB, LEU32ARG
  
RCV000016295

See Garel et al. (1975).

Walker et al. (2003) described heterozygosity for Hb Castilla in an 8-month-old boy with persistent hemolytic anemia.


.0045 HEMOGLOBIN CHANDIGARH

HBB, ASP94GLY
  
RCV000016296

Dash et al. (1989) described Hb Chandigarh in a 35-year-old carrier of beta-thalassemia who was the father of a child diagnosed to have homozygous beta-thalassemia. At that time, the patient was normocytic with normal values of hemoglobin, PCV, and RBC count. Two other hemoglobin variants with substitutions at asp94 had been described: Hb Barcelona (asp94 to his; 141900.0016) and Hb Bunbury (asp94 to asn; 141900.0035), both of which were described as high oxygen affinity Hb variants, with or without erythrocytosis. Dash and Das (2004) reported on the same patient observed 15 years later. He then had marked hepatosplenomegaly and was found to have polycythemia. The asp94 residue was known to form a salt bridge between its carboxyl group and the imidazolium ion of the histidine residue at the C terminus. The loss of this salt bridge appears to destabilize the deoxy structure and shift the equilibrium from the deoxy to the oxy configuration.


.0046 HEMOGLOBIN CHEMILLY

ERYTHROCYTOSIS 6, INCLUDED
HBB, ASP99VAL
  
RCV000016297...

.0047 HEMOGLOBIN CHEVERLY

HBB, PHE45SER
  
RCV000016298...

See Yeager et al. (1983). (Hb Hammersmith is beta-42 phe to ser. Despite the functional and structural similarities, the clinical manifestations of Hb Cheverly are much milder than those of Hb Hammersmith.)


.0048 HEMOGLOBIN CHICO

HBB, LYS66THR
  
RCV000016299...

See Shih et al. (1987). Hb Chico has diminished oxygen affinity (Bonaventura et al., 1991). Its oxygen-binding constant is about half that of normal. Bonaventura et al. (1991) presented data on the molecular basis of this altered property.


.0049 HEMOGLOBIN CHRISTCHURCH

HBB, PHE71SER
  
RCV000016300

.0050 HEMOGLOBIN CITY OF HOPE

HBB, GLY69SER
  
RCV000016301...

See Rahbar et al. (1984) and Kutlar et al. (1989). De Angioletti et al. (1992) detected Hb City of Hope by reversed phase high performance liquid chromatography in an asymptomatic carrier in Naples. The gly69-to-ser substitution, identified by fast atom bombardment mass spectrometry, was shown to be due to a TGG-to-TGA substitution by DNA sequencing. The mutation was associated with RFLP haplotype 9, instead of haplotype 1, as previously reported.


.0051 HEMOGLOBIN COCHIN-PORT ROYAL

HBB, HIS146ARG
  
RCV000016302

See Wajcman et al. (1975).

De Angioletti et al. (2002) described the comparable mutation in the delta chain of hemoglobin A, designated HBA2-Monreale (142000.0038).


.0052 HEMOGLOBIN COCODY

HBB, ASP21ASN
  
RCV000016303

.0053 HEMOGLOBIN COLLINGWOOD

HBB, VAL60ALA
  
RCV000016304

.0054 HEMOGLOBIN CONNECTICUT

HBB, ASP21GLY
  
RCV000016305

.0055 HEMOGLOBIN COVENTRY

HBB, LEU141DEL
  
RCV000016306

The proband was a child who appeared to have 3 different beta chains in addition to the delta chain of HbA2 and the gamma chain of HbF (Casey et al. (1976, 1978)). The child had Hb Sydney (beta 67 val-to-ala) and deletion of beta 141 leu. These were in different beta genes. The presence of 3 beta genes suggested to Lehmann (1978) that the beta Coventry chain is in fact a beta-delta fusion chain. Fay et al. (1993) offered the explanation of posttranslational modification of leu-141, probably a conversion to hydroxyleucine, which was not detected by standard amino acid analysis and sequencing methods. Of interest was the finding that not only Hb Sydney but also another substitution at the same codon, val67-to-gly in Hb Manukau, showed this feature. Hemoglobin Coventry was also found in association with Hb Atlanta (leu75-to-pro) (141900.0012).


.0056 HEMOGLOBIN COWTOWN

ERYTHROCYTOSIS 6, INCLUDED
HBB, HIS146LEU
  
RCV000016307...

This variant was named for Fort Worth, Texas. Polycythemia is produced. One member of the family was treated with P32 for presumed polycythemia rubra vera (Schneider, 1978; Schneider et al., 1979). This and about 40 other hemoglobin variants are associated with erythrocytes. See Perutz et al. (1984).


.0057 HEMOGLOBIN CRANSTON

HBB, 2-BP INS, CODON 144
  
RCV000016308

This hemoglobin was found in an asymptomatic woman with a compensated hemolytic state due to an unstable hemoglobin variant (Bunn et al., 1975). The hemoglobin had an abnormally long beta chain that, starting at amino acid 144, had the following sequence: lys-ser-ile-thr-lys-leu-ala-phe-leu-leu-ser-asn-phe-tyr-COOH. This is the first HbA variant known to contain isoleucine. Bunn et al. (1975) concluded that Hb Cranston probably arose by nonhomologous crossing-over between 2 normal beta chain genes, resulting in the insertion of 2 nucleotides (AG) at position 144, to produce a frame shift. Hb Wayne is thought to be a frame shift mutation involving the alpha chain. Hb Tak is another hemoglobin with abnormally long beta chain. Hb Constant Spring, Hb Koya Dora, and Hb Icaria are hemoglobins with abnormally long alpha chains. See Shaeffer et al. (1980).


.0058 HEMOGLOBIN CRETE

HBB, ALA129PRO
  
RCV000016309...

See Maniatis et al. (1979).

Christopoulou et al. (2004) identified a 1368G-C transversion in exon 3 of the beta-globin gene, resulting in an ala129-to-pro (A129P) substitution. Both the proband and her mother, who were found to be heterozygous for Hb Crete, presented with mild microcytic anemia and normal hemoglobin A2 levels and iron metabolism indices.


.0059 HEMOGLOBIN CRETEIL

ERYTHROCYTOSIS 6, INCLUDED
HBB, SER89ASN
  
RCV000016310...

Erythrocytosis results. See Thillet et al. (1976) and Poyart et al. (1978).


.0060 HEMOGLOBIN D (BUSHMAN)

HBB, GLY16ARG
  
RCV000016311

.0061 HEMOGLOBIN D (GRANADA)

HBB, GLU22VAL
  
RCV000016312...

.0062 HEMOGLOBIN D (IBADAN)

HBB, THR87LYS
  
RCV000016313...

.0063 HEMOGLOBIN D (IRAN)

HBB, GLU22GLN
  
RCV000016314...

.0064 HEMOGLOBIN D (OULED RABAH)

HBB, ASN19LYS
  
RCV000016321...

See Elion et al. (1973) and Ren et al. (1988).

Among 598 children from the Berber population of the Mzab, Merghoub et al. (1997) found HbC and Hb D (Ouled Rabah) in the same gene frequency (0.015). Hb D(Ouled Rabah) is considered a private marker of the Kel Kummer Tuaregs. Haplotype analysis suggested a single origin of the Hb D mutation. Genetic markers calculated from blood group data clustered Mozabites and Tuaregs with the other Berber-speaking groups, Arabic-speaking populations being more distant. However, they found no specific relationship between the Mozabites and Kel Kummers. Tuaregs in general exhibit features that tend to differentiate them from other Berber-speaking groups. Merghoub et al. (1997) concluded that Hb D(Ouled Rabah) may be specific for Berber-speaking populations. Merghoub et al. (1997) noted that the origin of the Berber people is not clearly established. North Africa was peopled around the sixteenth millennium B.C.; transition to agriculture occurred around 9500 to 7000 B.C., spreading from the Near East to Egypt. The Arab invasion in the seventh and eighth centuries brought Islamization and dispersal of the Berber culture. Present-day populations of North Africa are mostly Arabic-speaking, whatever their remote origin. Berbers, however, with their languages and customs, still live in small niches of northern Morocco and Algeria, and in some northern oases of the Sahara, including those of the Mzab (Algeria). The Tuaregs also speak Berber languages. They inhabit the south of the Sahara and have been involved for centuries in trans-Saharan trade. Tuaregs have their own culture that probably diverged from the Berber world through isolation.


.0065 HEMOGLOBIN D (PUNJAB)

HEMOGLOBIN D (CHICAGO)
HEMOGLOBIN D (LOS ANGELES)
HEMOGLOBIN D (NORTH CAROLINA)
HEMOGLOBIN D (PORTUGAL)
HEMOGLOBIN OAK RIDGE
HBB, GLU121GLN
  
RCV000016317...

See Benzer et al. (1958), Bowman and Ingram (1961), Stout et al. (1964), Schneider et al. (1968), Lehmann and Carrell (1969), Ozsoylu (1970), Imamura and Riggs (1972), Bunn et al. (1978), Trent et al. (1984), Worthington and Lehmann (1985), Husquinet et al. (1986), and Harano et al. (1987). Hemoglobin D (Punjab) is common worldwide. It is the most frequent abnormal hemoglobin in Xinjiang Uygur Autonomous Region of China (Li et al., 1986). Zeng et al. (1989) used the PCR method for population studies of this variant. Using PCR and direct sequencing, Schnee et al. (1990) demonstrated the predicted G-to-C substitution in codon 121.


.0066 HEMOGLOBIN DEER LODGE

HBB, HIS2ARG
  
RCV000016324...

.0067 HEMOGLOBIN DETROIT

HBB, LYS95ASN
  
RCV000016325...

.0068 HEMOGLOBIN DJELFA

HBB, VAL98ALA
  
RCV000016326

.0069 HEMOGLOBIN DOHA

HBB, NH2 EXTENSION, VAL1GLU
  
RCV000016327

Kamel et al. (1985) investigated a Qatari family with an electrophoretically fast-moving hemoglobin that they found contained an abnormal beta chain with the sequence met-glu-his-leu at the NH2-end. Substitution of glutamic acid for valine at beta 1 apparently prevented removal of the initiator methionine. The methionine was blocked by a molecule not completely identified. No clinical consequences were observed in heterozygotes.

This variant was numbered based on the first amino acid of the mature protein. In the gene-based system of counting, this variant is VAL2GLU.


.0070 HEMOGLOBIN DUARTE

HBB, ALA62PRO
  
RCV000016328

.0071 HEMOGLOBIN E

BETA-PLUS-THALASSEMIA
BETA-E-THALASSEMIA
MALARIA, RESISTANCE TO, INCLUDED
HBB, GLU26LYS
  
RCV000016329...

This mutation is a cause of beta-plus-thalassemia (613985). See Hunt and Ingram (1961), Shibata et al. (1962), Blackwell et al. (1970), Fairbanks et al. (1980), Benz et al. (1981), and Kazazian et al. (1984).

Orkin et al. (1982) reported the complete nucleotide sequence of a beta-E-globin gene. They found a GAG-to-AAG change in codon 26 as the only abnormality. Expression of the beta-E gene was tested by introducing it into HeLa cells. Two abnormalities of RNA processing were shown: slow excision of intervening sequence-1 and alternative splicing into exon 1 at a cryptic donor sequence within which the codon 26 nucleotide substitution resides.

Antonarakis et al. (1982) used the Kazazian haplotype approach of analyzing DNA polymorphisms in the beta-globin cluster to present evidence that the beta-E mutation occurred at least twice in Southeast Asia. Thein et al. (1987) demonstrated that the GAG-to-AAG change could be recognized by the restriction enzyme MnlI which cleaves DNA at the sequence 3-prime-GGAG-5-prime.

Rey et al. (1991) described SE disease in 3 black American children of Haitian origin. They pointed out that the disorder is probably more benign than SC disease, SO(Arab) disease, and SC(Harlem) disease, all of which have increased risk of the complications of sickling including pneumococcal sepsis.

Rees et al. (1996) reported a girl homozygous for Hb E with severe anemia and anisopoikilocytosis, who was also homozygous for pyrimidine 5-prime nucleotidase deficiency (P5N; 266120). In erythrocytes deficient for P5N, the stability of the Hb E was decreased.

Hemoglobin E is very common in parts of Southeast Asia. Chotivanich et al. (2002) examined the possible protective role of Hb E and other prevalent inherited hemoglobin abnormalities against malaria (611162) in Thailand. They assessed the effect of Hb E by means of a mixed erythrocyte invasion assay. In vitro, starting at 1% parasitemia, Plasmodium falciparum preferentially invaded normal (HbAA) compared to abnormal hemoglobin red blood cells, including those heterozygous and homozygous for Hb E. The heterozygote HbAE cells differed markedly from all the other cells tested, with invasion restricted to approximately 25% of the red blood cells. Despite their microcytosis, AE heterozygous cells were functionally relatively normal in contrast to the red blood cells from the other hemoglobinopathies studied. Chotivanich et al. (2002) interpreted these findings as suggesting that HbAE erythrocytes have an unidentified membrane abnormality that renders most of the red blood cell population relatively resistant to invasion by P. falciparum. This would not protect from uncomplicated malaria infections but would prevent the development of heavy parasite burdens and was considered consistent with the 'Haldane hypothesis' of heterozygote protection against severe malaria for Hb E.

The Hb E variant is concentrated in parts of Southeast Asia where malaria is endemic, and Hb E carrier status confers some protection against Plasmodium falciparum malaria. To examine the effect of natural selection on the pattern of linkage disequilibrium (LD) and to infer the evolutionary history of the Hb E variant, Ohashi et al. (2004) analyzed biallelic markers surrounding the Hb E variant in a Thai population. Pairwise LD analysis of Hb E and 43 surrounding biallelic markers revealed LD of Hb E extending beyond 100 kb, whereas no LD was observed between non-Hb E variants and the same markers. The inferred haplotype network suggested a single origin of the Hb E variant in the Thai population. Forward-in-time computer simulations under a variety of selection models indicated that the Hb E variant arose 1,240 to 4,440 years ago. Thus, the Hb E mutation occurred recently and allele frequency increased rapidly. The study demonstrated that a high resolution LD map across the human genome can detect recent variants that have been subjected to positive selection.

The highest frequencies of the Hb E gene in large population samples, approximately 0.3, had been observed in the southern part of northeastern Thailand. Even higher frequencies were observed by Flatz et al. (2004) in Austroasiatic populations in southern Laos. One frequency was as high as 0.433 in a population of Sekong Province.

As in other areas of Southeast Asia, hemoglobin E is a very common hemoglobin variant in India, where the highest prevalence of hemoglobin E has been observed in the northeastern regions. In West Bengal, carrier frequency varies from 5 to 35% in different subpopulations, whereas in Assam and Meghalaya, the heterozygous frequency ranges from 27 to 51%. Individuals heterozygous for hemoglobin E have normal or near-normal mean corpuscular volume (MCV) with 27 to 31% of the abnormal Hb in peripheral blood. Homozygosity for hemoglobin E is commonly benign, characterized by mild hypochromic microcytic anemia with the presence of target cells. Edison et al. (2005) observed hyperbilirubinemia among patients with homozygosity for the hemoglobin E gene in the Indian population, with jaundice being the major complaint at presentation. A study of UGT1A1 gene polymorphism showed that the variant TA(7) in the promoter region of the UGT1A1 gene (191740.0011) was associated with hyperbilirubinemia in homozygous HbE patients.

The role of the TA(7) polymorphism of UGT1A1 in the determination of jaundice and gallstones in hemoglobin E beta-thalassemia had been pointed out by Premawardhena et al. (2001) in studies from Sri Lanka. The same group (Premawardhena et al., 2003) studied the global distribution of length polymorphisms of the promoters of the UGT1A1 gene. They found that homozygosity for the TA(7) allele occurred in 10 to 25% of the populations of Africa and the Indian subcontinent, with a variable frequency in Europe. It occurred at a much lower frequency in Southeast Asia, Melanesia, and the Pacific Islands, ranging from 0 to 5%. African populations showed a much greater diversity of length alleles than other populations. These findings defined those populations with a high frequency of hemoglobin E beta-thalassemia and related disorders that are at increased risk for hyperbilirubinemia and gallbladder disease. Beutler et al. (1998) had suggested that the wide diversity in the frequency of the UGT1A1 promoter alleles might reflect a balanced polymorphism mediated through the protective effect of bilirubin against oxidative damage.

O'Donnell et al. (2009) studied Sri Lankan patients with HbE beta-thalassemia for exposure to malaria caused by P. falciparum or P. vivax. They found that there were high frequencies of antibodies to both malaria parasites, as well as DNA-based evidence of current infection with P. vivax. Comparisons with age-matched controls showed that there was a higher frequency of antibodies in thalassemic patients, particularly against P. vivax and in young children, that was unlikely to be related to transfusion. A higher frequency was also found in patients who had undergone splenectomy. O'Donnell et al. (2009) proposed that patients with HbE beta-thalassemia may be more prone to malaria, particularly P. vivax malaria.

The estimated number of worldwide annual births of patients with HbE beta-thalassemia is 19,128 (Modell and Darlison, 2008 and Weatherall, 2010).


.0072 HEMOGLOBIN E (SASKATOON)

HBB, GLU22LYS
  
RCV000016333...

See Vella et al. (1967) and Gonzalez-Redondo et al. (1987). Gurgey et al. (1990) found compound heterozygosity for this mutation and beta-thalassemia of type IVS1-6 (141900.0360). Igarashi et al. (1995) identified Hb E-Saskatoon in a Japanese male. Igarashi et al. (1995) reported what they stated was the first case of Hb-E (Saskatoon) in a Japanese male.

Birben et al. (2001) described Hb E-Saskatoon in homozygous state in a 30-year-old Turkish woman. The consanguineous parents were heterozygotes for the abnormal hemoglobin. The heterozygous son of the proband had mild anemia; physical examination of the child and family members revealed no abnormalities. The parameters of routine hematologic studies were within normal limits.


.0073 HEMOGLOBIN EDMONTON

HBB, THR50LYS
   RCV000016334

See Labossiere et al. (1971). Landin et al. (1996) pointed out that 2 nucleotide substitutions in codon 50, either ACT to AAA, or ACT to AAG, would be required to produce this amino acid substitution. The same is true for the amino acid substitutions in Hb Bristol (141900.0030) and Hb Beckman (141900.0442) among the beta-globin variants and Hb J-Kurosh (141800.0066), an alpha-globin variant.


.0074 HEMOGLOBIN EXTREMADURA

HBB, VAL133LEU
  
RCV000016335

In a Spanish female with mild hemolytic anemia, Villegas et al. (1989) demonstrated this mildly unstable hemoglobin.


.0075 HEMOGLOBIN FANNIN-LUBBOCK

HBB, VAL111LEU AND GLY119ASP
  
RCV000016336...

See Moo-Penn et al. (1976). In 5 apparently, unrelated Spanish adults, Qin et al. (1994) found a fast-moving hemoglobin variant and observed a GGC-to-GAC mutation at codon 119 which had previously been identified as the abnormality in Hb Fannin-Lubbock. In addition, however, they found a GTC-to-CTC change at codon 111 which led to a val-to-leu substitution. Protein analysis in one of the individuals confirmed that the 2 mutations were located on the same chromosome. Qin et al. (1994) suggested that some other known variants may carry an additional mutation that results in an electrophoretically silent amino acid substitution which may, however, have an effect on the physicochemical properties of the protein. In the case of Hb Fannin-Lubbock, it appeared likely that the val111-to-leu substitution, rather than the gly119-to-asp replacement, was the cause of the instability of the variant. The Hb Fannin-Lubbock variant in these Spanish families had a normal oxygen affinity.


.0076 HEMOGLOBIN FREIBURG

HBB, VAL23DEL
  
RCV000016337

Deletion of val23 from otherwise normal beta chain probably occurred through triplet deletion resulting from unequal crossing-over between 2 normal beta loci in 1 parent of the proband. Two of 3 living children of the proband also had the abnormal hemoglobin, which was accompanied by slight cyanosis in all 3 and by a hemolytic process in the proband. See Jones et al. (1966) and Horst et al. (1988).


.0077 HEMOGLOBIN FUKUOKA

HBB, HIS2TYR
  
RCV000016339

.0078 HEMOGLOBIN FUKUYAMA

HBB, HIS77TYR
  
RCV000016340...

.0079 HEMOGLOBIN G (ACCRA)

HBB, ASP79ASN
  
RCV000016341...

There is no clinical or hematologic abnormality in the homozygote. See Edington et al. (1955), Gammack et al. (1961), Lehmann et al. (1964), and Milner (1967).


.0080 HEMOGLOBIN G (COPENHAGEN)

HBB, ASP47ASN
  
RCV000016342...

.0081 HEMOGLOBIN G (COUSHATTA)

HEMOGLOBIN G (SASKATOON)
HEMOGLOBIN G (HSIN-CHU)
HEMOGLOBIN G (TAEGU)
HBB, GLU22ALA
  
RCV000016343...

.0082 HEMOGLOBIN G (FERRARA)

HBB, ASN57LYS
  
RCV000016347...

.0083 HEMOGLOBIN G (GALVESTON)

HEMOGLOBIN G (PORT ARTHUR)
HEMOGLOBIN G (TEXAS)
HBB, GLU43ALA
  
RCV000016348...

See Bowman et al. (1962, 1964).


.0084 HEMOGLOBIN G (HSI-TSOU)

HBB, ASP79GLY
  
RCV000016351

.0085 HEMOGLOBIN G (MAKASSAR)

HBB, GLU6ALA
   RCV000016352...

.0086 HEMOGLOBIN G (SAN JOSE)

HBB, GLU7GLY
  
RCV000016353...

This hemoglobin oxy was first described in a family of Calabrian origin by Schwartz et al. (1957). The molecular defect was demonstrated by Hill et al. (1960). Brancati et al. (1989) reported a case of homozygosity in a healthy male with normal hematologic findings. See Hill and Schwartz (1959), Ricco et al. (1974), Wilson et al. (1980), and Schiliro et al. (1981).


.0087 HEMOGLOBIN G (SZUHU)

HEMOGLOBIN GIFU
HBB, ASN80LYS
  
RCV000016354...

See Blackwell et al. (1969), Imai et al. (1970), Kaufman et al. (1975), Welch (1975) and Romero et al. (1985). Schiliro et al. (1991) found this abnormal hemoglobin in 4 members from 2 generations of a Sicilian family.


.0088 HEMOGLOBIN G (TAIPEI)

HBB, GLU22GLY
  
RCV000016356...

.0089 HEMOGLOBIN G (TAIWAN-AMI)

HBB, GLY25ARG
  
RCV000016357

.0090 HEMOGLOBIN GAINESVILLE-GA

HBB, GLY46ARG
  
RCV000016358

.0091 HEMOGLOBIN GAVELLO

HBB, ASP47GLY
  
RCV000016359

.0092 HEMOGLOBIN GEELONG

HEMOGLOBIN JINAN
HBB, ASN139ASP
  
RCV000016360...

.0093 HEMOGLOBIN GENOVA

HEMOGLOBIN HYOGO
HBB, LEU28PRO
  
RCV000016362...

.0094 HEMOGLOBIN GRANGE-BLANCHE

HBB, ALA27VAL
  
RCV000016364...

.0095 HEMOGLOBIN GUN HILL

HBB, 15-BP DEL
  
RCV000016365

Deletion of amino acid residues 93-97 inclusive of beta chain probably through unequal crossing over. This unstable hemoglobin also has absence of half of the normal complement of heme. Other unstable hemoglobins include Hb Zurich, Hb Koln, Hb Geneva, Hb Sydney, Hb Hammersmith and Hb Sinai. (It is possible that the deletion is 91-95 or 92-96 rather than 93-97.) See Bradley et al. (1967) and Rieder and Bradley (1968). See Hb Koriyama (141900.0152).


.0096 HEMOGLOBIN HACETTEPE

HEMOGLOBIN COMPLUTENSE
HBB, GLN127GLU
  
RCV000016366...

.0097 HEMOGLOBIN HAFNIA

HBB, HIS116GLN
  
RCV000016368

By isoelectric focusing (IEF) of red cell hemolysates, this hemoglobin variant simulates glycated hemoglobin (HbA1c). This is the first mutation discovered at beta 116. It was first found in a 6-year-old boy with diabetes mellitus; 5 nondiabetic members of the family had the same hemoglobin variant (Blanke et al., 1988). (Hafnia is Latin for Copenhagen.)

During neonatal screening in Belgium, Cotton et al. (2000) found a newborn of Brazilian origin with Hb Hafnia. Both he and his mother were heterozygous for a CAT-to-CAA transversion at codon 116. Both were clinically and hematologically normal.


.0098 HEMOGLOBIN HAMADAN

HBB, GLY56ARG
  
RCV000016369...

See Rahbar et al. (1975).

Akar et al. (2003) described the first observation of homozygous Hb Hamadan in a Turkish family. In this family 1 member was a compound heterozygote for Hb Hamadan and beta-thalassemia due to a -29A-G promoter mutation (141900.0379). Neither homozygous Hb Hamadan nor a combination with beta-thalassemia appeared to have clinical significance.


.0099 HEMOGLOBIN HAMILTON

HBB, VAL11ILE
  
RCV000016370...

See Manca et al. (1987) and Wong et al. (1984). Manca et al. (1992) described an easy PCR-based method for demonstration of the mutation. They demonstrated the predicted G-to-A transition at codon 11 which abolishes a MaeIII restriction site. This mutation, which is rather common among Sardinians, involves one of the 5 CpG dinucleotides of the beta-globin gene.


.0100 HEMOGLOBIN HAMMERSMITH

HEMOGLOBIN CHIBA
HEINZ BODY HEMOLYTIC ANEMIA
HBB, PHE42SER
  
RCV000016371...

The normal phenylalanine at this site apparently 'stabilizes' the heme with which it is in contact. The substitution of serine leads to severe Heinz body hemolytic anemia. See Dacie et al. (1967), Ohba et al. (1975), and Rahbar et al. (1981). Dianzani et al. (1991) demonstrated a de novo phe42-to-ser mutation using the chemical cleavage of mismatch method (CCM) of Cotton et al. (1988). The responsible substitution was a TTT-to-TCT change. The report of rare cases of this hemoglobinopathy in different ethnic groups also supports the occurrence of independent mutations.


.0101 HEMOGLOBIN HAZEBROUCK

HBB, THR38PRO
  
RCV000016374

.0102 HEMOGLOBIN HEATHROW

ERYTHROCYTOSIS 6, INCLUDED
HBB, PHE103LEU
  
RCV000016375...

Hb Heathrow is a cause of erythrocytosis because of increase in oxygen affinity. The mutation occurs in the same codon as that in Hb Saint Nazaire (141900.0436).

See White et al. (1973).


.0103 HEMOGLOBIN HELSINKI

ERYTHROCYTOSIS 6, INCLUDED
HBB, LYS82MET
  
RCV000016376...

This is a cause of familial erythrocytosis. See Ikkala et al. (1976).


.0104 HEMOGLOBIN HENRI MONDOR

HBB, GLU26VAL
  
RCV000016377

.0105 HEMOGLOBIN HIJIYAMA

HBB, LYS120GLU
  
RCV000016378

.0106 HEMOGLOBIN HIKARI

HBB, LYS61ASN
  
RCV000016379...

Heterozygotes have about 60% hemoglobin Hikari. See Shibata and Iuchi (1962) and Shibata et al. (1964).


.0107 HEMOGLOBIN HIMEJI

HBB, ALA140ASP
  
RCV000016380...

This hemoglobin was found in a diabetic because its N-terminal glycation was about 3 times that of the normal (Ohba et al., 1986).


.0108 HEMOGLOBIN HINSDALE

HBB, ASN139LYS
  
RCV000016381...

.0109 HEMOGLOBIN HIROSE

HBB, TRP37SER
  
RCV000016382

.0110 HEMOGLOBIN HIROSHIMA

ERYTHROCYTOSIS 6, INCLUDED
HBB, HIS146ASP
  
RCV000016383...

Associated with increased oxygen affinity, decreased Bohr effect, and erythremia. (The substitution was formerly thought to be at residue 143.) See Hamilton et al. (1969) and Perutz et al. (1971).


.0111 HEMOGLOBIN HOFU

HBB, VAL126GLU
  
RCV000016384...

.0112 HEMOGLOBIN HOPE

HBB, GLY136ASP
  
RCV000016385...

See Minnich et al. (1965), Steinberg et al. (1974, 1976), Charache et al. (1979), Harano et al. (1983), Martinez and Colombo (1984), and Enoki et al. (1989). In a Thai Mien family, Pillers et al. (1992) observed Hb Hope in compound heterozygous state with Hb E. Previous reports of Hb Hope had involved predominantly black Americans, blacks who lived in Cuba, or natives of Mali who lived in France.

Ingle et al. (2004) analyzed interactions of Hb Hope with Hb S (141900.0243), other variant hemoglobins, and thalassemia.


.0113 HEMOGLOBIN HOSHIDA

HEMOGLOBIN CHAYA
HBB, GLU43GLN
  
RCV000016387

See Iuchi et al. (1978) and Shibata et al. (1980). Plaseska et al. (1991) observed this mutation, due to a GAG-to-CAG change at codon 43, in a Yugoslavian family.


.0114 HEMOGLOBIN HOTEL-DIEU

ERYTHROCYTOSIS 6, INCLUDED
HBB, ASP99GLY
  
RCV000016388...

.0115 HEMOGLOBIN I (HIGH WYCOMBE)

HBB, LYS59GLU
  
RCV000016389

See Boulton et al. (1970), Lacombe et al. (1987), and Wilkinson et al. (1987).

Hamaguchi et al. (2000) reported the first case of hemoglobin I (High Wycombe) in Japan. It was suspected because of a discrepancy between blood glucose status and glycated hemoglobin measurements in a 55-year-old diabetic female.


.0116 HEMOGLOBIN I (TOULOUSE)

HEMOGLOBIN TOULOUSE
HBB, LYS66GLU
  
RCV000016390...

.0117 HEMOGLOBIN INDIANAPOLIS

HEINZ BODY HEMOLYTIC ANEMIA
HBB, CYS112ARG
  
RCV000016392...

Adams et al. (1978, 1979) studied father and daughter with a clinical picture of beta-thalassemia which was due to labile beta-chains resulting in Heinz body formation in normoblasts. The changes in the beta-chains were posttranslational. Baiget et al. (1986) and De Biasi et al. (1988) described 2 new families with the cys112-to-arg mutation. In these families the carriers were not anemic, had normal chromic and normocytic red cells, and displayed only mild reticulocytosis. This prompted Coleman et al. (1991) to restudy the original family with the finding that the mutation in fact was leu106-to-arg. In order to avoid confusion, they renamed the original mutation Hb Terre Haute (see 141900.0398).


.0118 HEMOGLOBIN ISTANBUL

HEMOGLOBIN SAINT ETIENNE
HBB, HIS92GLN
  
RCV000016395

One patient had an apparent new mutation; the father was 41 years old and the mother 36 at the patient's birth (Aksoy et al. (1972)). See Beuzard et al. (1972) and Aksoy and Erdem (1979).

De Weinstein et al. (2000) described this hemoglobin variant in a 36-year-old Argentinian female of Spanish-Portuguese origin. She presented with chronic hemolytic anemia, jaundice, splenomegaly, and gallstones from childhood. She required blood transfusion during her only pregnancy at the age of 23. She underwent splenectomy and cholecystectomy when she was 33 years old. Her 13-year-old son also presented with chronic hemolytic anemia, jaundice, and splenomegaly. It was the third observation of this hemoglobin variant. In the first 2 cases, origination was by de novo mutation. This was the first case in which the precise DNA change was identified: codon 92 was changed from CAC (his) to CAG (gln).


.0119 HEMOGLOBIN J (ALTGELD GARDENS)

HBB, HIS92ASP
  
RCV000016396

See Adams et al. (1975, 1978).


.0120 HEMOGLOBIN J (AMIENS)

HBB, LYS17ASN
  
RCV000016397

.0121 HEMOGLOBIN J (ANTAKYA)

HBB, LYS65MET
  
RCV000016398...

.0122 HEMOGLOBIN J (AUCKLAND)

HBB, GLY25ASP
  
RCV000016399

.0123 HEMOGLOBIN J (BALTIMORE)

HEMOGLOBIN J (IRELAND)
HEMOGLOBIN J (TRINIDAD)
HEMOGLOBIN J (GEORGIA)
HEMOGLOBIN N (NEW HAVEN 2)
HBB, GLY16ASP
  
RCV000016400...

.0124 HEMOGLOBIN J (BANGKOK)

HEMOGLOBIN J (KORAT)
HEMOGLOBIN J (MANADO)
HEMOGLOBIN J (MEINUNG)
HBB, GLY56ASP
  
RCV000016405...

.0125 HEMOGLOBIN J (CAIRO)

HBB, LYS65GLN
  
RCV000016409

.0126 HEMOGLOBIN J (CALABRIA)

HEMOGLOBIN J (COSENZA)
HEMOGLOBIN J (BARI)
HBB, GLY64ASP
  
RCV000016410...

.0127 HEMOGLOBIN J (CHICAGO)

HBB, ALA76ASP
  
RCV000016413

See Romain et al. (1975). This hemoglobin was discovered in a 2-year-old black child from Chicago, who was hospitalized for iron deficiency anemia. The second case was reported in a Spanish family by Arrizabalaga et al. (1998).


.0128 HEMOGLOBIN J (CORDOBA)

HBB, LYS95MET
  
RCV000016414

.0129 HEMOGLOBIN J (DALOA)

HBB, ASN57ASP
  
RCV000016415

.0130 HEMOGLOBIN J (GUANTANAMO)

HBB, ALA128ASP
  
RCV000016416

The first reported cases were in a Cuban family of African ancestry (Martinez et al., 1977). Wajcman et al. (1988) described a case from Benin in Nigeria. Also see Zhu et al. (1988) and Sciarratta et al. (1990). Yamagishi et al. (1993) identified this mutation in a Japanese family during assay of glycated hemoglobins by ion exchange high performance liquid chromatography. No anemia or hemolysis was observed in the affected members of the family, although one member had a decreased haptoglobin value.


.0131 HEMOGLOBIN J (IRAN)

HBB, HIS77ASP
  
RCV000016417...

See Gammack et al. (1961), Rahbar et al. (1967), and Delanoe-Garin et al. (1986). Bircan et al. (1990) observed compound heterozygosity of this variant with Hb N (Baltimore) (141900.0188).


.0132 HEMOGLOBIN J (KAOHSIUNG)

HEMOGLOBIN J (HONOLULU)
HBB, LYS59THR
  
RCV000016418...

See Blackwell et al. (1971) and Blackwell et al. (1972). Chang et al. (1992) described a new RFLP created by this substitution.


.0133 HEMOGLOBIN J (LENS)

HBB, ALA13ASP
  
RCV000016420

.0134 HEMOGLOBIN J (LOME)

HBB, LYS59ASN
  
RCV000016421...

.0135 HEMOGLOBIN J (LUHE)

HBB, LYS8GLN
  
RCV000016422

.0136 HEMOGLOBIN J (RAMBAM)

HEMOGLOBIN J (CAMBRIDGE)
HBB, GLY69ASP
  
RCV000016423...

See Salomon et al. (1965) and Sick et al. (1967).

Plaseska-Karanfilska et al. (2000) described Hb Rambam in a family in Argentina. It was combined in compound heterozygous state with a form of beta-zero-thalassemia due to deletion of 2 nucleotides (CT) from codon 5. The latter mutation had been found among Bulgarian, Turkish, Greek, Macedonian, North African, and Middle Eastern populations, and in some populations of the Indian subcontinent.


.0137 HEMOGLOBIN J (SICILIA)

HBB, LYS65ASN
  
RCV000016425

.0138 HEMOGLOBIN J (TAICHUNG)

HBB, ALA129ASP
  
RCV000016426...

.0139 HEMOGLOBIN JIANGHUA

HBB, LYS120ILE
  
RCV000016427

.0140 HEMOGLOBIN JOHNSTOWN

HBB, VAL109LEU
  
RCV000016428...

See Jones et al. (1990).

Hb Johnstown, caused by a change of codon 109 in exon 3 of the HBB gene from GTG (val) to CTG (leu) (val109 to leu), is a high oxygen affinity hemoglobin variant. Feliu-Torres et al. (2004) identified Hb Johnstown in association with beta-zero-thalassemia of the IVS1AS-1G-A (141900.0356) type in an 8-year-old girl referred because of erythrocytosis and a left-shifted oxygen dissociation curve. The mother was found to be heterozygous for the Hb variant and the father was a beta-zero-thalassemia carrier. This Hb variant had normal electrophoresis. The erythrocytosis and low values for actual P50 due to Hb Johnstown were more marked due to the coinheritance of the beta-zero-thalassemia.


.0141 HEMOGLOBIN K (CAMEROON)

HBB, ALA129GLU OR ALA129ASP
   RCV000016426...

.0142 HEMOGLOBIN K (IBADAN)

HBB, GLY46GLU
  
RCV000016430...

See Allan et al. (1965). Castagnola et al. (1990) found this variant in an Italian family.


.0143 HEMOGLOBIN K (WOOLWICH)

HBB, LYS132GLN
  
RCV000016431...

.0144 HEMOGLOBIN KAIROUAN

HEMOGLOBIN MONROE
HBB, ARG30THR
  
RCV000016432...

Codon 30 (for arginine) is interrupted between the second and third nucleotide by the first intervening sequences of 130 nucleotides. Modifications of the consensus sequence of the donor-splice site of IVS1 will affect the process of splicing. In hemoglobin Monroe, the G-to-C mutation occurred at a nucleotide position adjacent to the GT dinucleotide required for splicing; this substitution would be expected to cause greatly decreased splicing and severe beta-plus-thalassemia, as was observed in the family reported by Gonzalez-Redondo et al. (1989). In a Mediterranean type of beta-plus-thalassemia, Vidaud et al. (1989) found a G-to-C transversion in codon 30 that altered both beta-globin pre-mRNA splicing and the structure of the hemoglobin product. Presumably, this G-to-C transversion at position -1 of intron 1 reduced severely the utilization of the normal 5-prime splice site, since the level of the arg-to-thr mutant hemoglobin (designated hemoglobin Kairouan) was very low in heterozygotes (2% of total hemoglobin). Since no natural mutations of the guanine located at position -1 of the CAG/GTAAGT consensus sequence had been isolated previously, Vidaud et al. (1989) studied the role of this nucleotide in cell-free extracts. They found that correct splicing was 98% inhibited. Thus, the last residue of exon 1 plays a role at least equivalent to that of the intron residue at position 5.


.0145 HEMOGLOBIN KANSAS

HEMOGLOBIN REISSMANN ET AL.
HBB, ASN102THR
  
RCV000016434

This hemoglobin variant has a low oxygen affinity, resulting in cyanosis. See Reissmann et al. (1961) and Bonaventura and Riggs (1968).


.0146 HEMOGLOBIN KEMPSEY

ERYTHROCYTOSIS 6, INCLUDED
HBB, ASP99ASN
  
RCV000016436...

.0147 HEMOGLOBIN KENITRA

HBB, GLY69ARG
  
RCV000016437

.0148 HEMOGLOBIN KHARTOUM

HBB, PRO124ARG
  
RCV000016438...

.0149 HEMOGLOBIN KNOSSOS

BETA-PLUS-THALASSEMIA
BETA-KNOSSOS-THALASSEMIA
HBB, ALA27SER
  
RCV000016439...

See Arous et al. (1982), Rouabhi et al. (1983), Galacteros et al. (1984), Elwan et al. (1987), and Kutlar et al. (1989). Hemoglobin Knossos is a cause of beta-thalassemia (613985), as is hemoglobin E. Orkin et al. (1984) isolated the beta(Knossos) gene and examined its expression in HeLa cells. Using a cryptic splice sequence that is enhanced by the Knossos substitution, they found that some beta(Knossos) transcripts were abnormally processed. In addition to Hb E, a silent substitution at beta 24 causes thalassemia by abnormal RNA processing.


.0150 HEMOGLOBIN KOFU

HBB, THR84ILE
  
RCV000016442

.0151 HEMOGLOBIN KOLN

HEMOGLOBIN UBE-1
HEMOGLOBIN SAN FRANCISCO (PACIFIC)
HEINZ BODY HEMOLYTIC ANEMIA
HBB, VAL98MET
  
RCV000016443...

See Shibata et al. (1961), Pribilla (1962), Hutchison et al. (1964), Pribilla et al. (1965), Carrell et al. (1966), Jackson et al. (1967), Jones et al. (1967), Woodson et al. (1970), Miller et al. (1971), Lie-Injo et al. (1972), and Ohba et al. (1973). Bradley et al. (1980) described a convincing instance of gonadal mosaicism accounting for an unusual pedigree pattern in a family with Hb Koln. Normal parents had 2 affected children and each of these 2 children had an affected child. This is the most common form of unstable hemoglobin. Horst et al. (1986) prepared DNA of 19 nucleotides, corresponding in length to the normal and mutant gene sequences, and demonstrated its use for the direct assay of the beta-Koln gene. The use of synthetic oligonucleotides established that the Hb Koln mutation is due to a G-to-A transition.

Landin et al. (1994) found Hb Koln as a new mutation in 3 independent cases of chronic hemolytic anemia in Sweden. The 2 children and 1 adult had partially compensated hemolysis and presented with aggravated hemolysis during acute infections in childhood. In 1 patient, acute B19 parvovirus infection induced an aplastic crisis. Diagnosis was based on hemoglobin instability testing and isoelectric focusing of hemoglobin dimers. Landin et al. (1994) demonstrated that PCR-RFLP can be used in diagnosis.

Chang et al. (1998) reported the first case of Hb Koln in the Chinese population.


.0152 HEMOGLOBIN KORIYAMA

HBB, 15-BP INS
   RCV000016447

See Kawata et al. (1988). Whereas 5 amino acid residues are deleted in Hb Gun Hill (141900.0095), 5 amino acid residues are inserted at the corresponding site in Hb Koriyama.


.0153 HEMOGLOBIN KORLE-BU

HBB, ASP73ASN
  
RCV000016286...

Since this same substitution is present with the sickle hemoglobin change as one of the two defects in hemoglobin C(Harlem), Konotey-Ahulu et al. (1968) suggested that the latter hemoglobin may have arisen by intracistronic crossing-over in an individual with the Korle-Bu gene on one chromosome and the sickle gene on the other. See Konotey-Ahulu et al. (1968) and Honig et al. (1983). Nagel et al. (1993) showed that compound heterozygosity for hemoglobin Korle-Bu (HbKB) and HbC (141900.0038) is associated with moderate chronic hemolytic anemia with microcytosis. They found that in vitro hemoglobin crystals formed within 2 minutes compared with 30 minutes for a mixture of 40% HbC and 60% HbS and within 180 minutes for 40% HbC with 60% HbA. The crystals were cubic in contrast with the tetragonal crystals observed in CC and SC disease. They concluded that the hemolysis observed in the HbKB/C compound heterozygote is likely to be secondary to the acceleration of Hb crystallization.


.0154 HEMOGLOBIN LA DESIRADE

HBB, ALA129VAL
  
RCV000016450...

.0155 HEMOGLOBIN LAS PALMAS

HBB, SER49PHE
  
RCV000016451...

.0156 HEMOGLOBIN LEIDEN

HBB, GLU6DEL OR GLU7DEL
  
RCV000016452...

.0157 HEMOGLOBIN LINCOLN PARK

HBB/HBD ANTI-LEPORE
HBB, HBB/HBD FUSION, HBD137DEL
  
RCV000016453...

See Honig et al. (1978). A beta-delta (anti-Lepore) variant found in a Mexican family, its amino acid structure of the non-alpha polypeptide indicated a crossover between amino acids 22 and 50. Honig et al. (1978) postulated a series of intergenic crossovers. The residue corresponding to the 137th in the delta chain is deleted. See Hb P(Nilotic).


.0158 HEMOGLOBIN LINKOPING

HEMOGLOBIN MEILAHTI
HBB, PRO36THR
  
RCV000016455...

See Jeppsson et al. (1984) and Ali et al. (1988). This variant was detected by oxygen equilibrium measurements and confirmed by IEF in Finns with erythrocytosis (Berlin et al., 1987) and in Americans of Finnish extraction (Jones et al., 1986). Wada et al. (1987) stated that 'in Finland, there are many patients with benign familial erythrocytosis, some of whom have Hb Helsinki' (141900.0103).


.0159 HEMOGLOBIN LITTLE ROCK

ERYTHROCYTOSIS 6, INCLUDED
HBB, HIS143GLN
  
RCV000641506

See Bromberg et al. (1973) and Francina et al. (1987). Heterozygotes have marked erythrocytosis as in the case of Hb Chesapeake, J (Capetown), Malmo, Rainier, Bethesda, Yakima, Kempsey, and Hiroshima.


.0160 HEMOGLOBIN LOUISVILLE

HEMOGLOBIN BUCURESTI
HBB, PHE42LEU
  
RCV000016458

This hemoglobin shows decreased stability on warming to 65 degrees C and an increased tendency to dissociate in the presence of sulfhydryl group-blocking agents. Clinically, it results in mild hemolytic anemia. See Keeling et al. (1971), Bratu et al. (1971), and Villegas et al. (1989).


.0161 HEMOGLOBIN LUFKIN

HBB, GLY29ASP
  
RCV000016460

See Schmidt et al. (1977) and Shimizu et al. (1988). Hb Lufkin is unstable, causing a mild but well-compensated hemolytic anemia. It was initially described in a black American boy from Texas. Gu et al. (1995) found this variant in combination with HbS in a black child who had a mild form of sickle cell disease, comparable to SC or SE disease.


.0162 HEMOGLOBIN LYON

HBB, LYS17DEL AND VAL18DEL
  
RCV000016461

Deletion of beta 17-18 (lys-val). See Cohen-Solal et al. (1974).


.0163 HEMOGLOBIN M (MILWAUKEE 1)

METHEMOGLOBINEMIA, BETA TYPE, INCLUDED
HBB, VAL67GLU
  
RCV000016462...

For a discussion of methemoglobinemia (617971) caused by Hb M (Milwaukee 1), see Gerald and Efron (1961), Hayashi et al. (1969), Perutz et al. (1972), and Horst et al. (1983). This is now usually called simply Hb M (Milwaukee) since Hb M (Milwaukee-2) has been shown to be the same as Hb M (Hyde Park). The family reported by Pisciotta et al. (1959) was of Italian extraction. Hb M (Milwaukee) was also described in a German family by Kohne et al. (1977). Oehme et al. (1983) followed the mutant beta-globin gene through 3 generations of this family by direct SstI analysis at the gene level. The molecular defect is a transversion T to A and because of the known recognition sequence of SstI, the nucleotide sequence corresponding to amino acids 67 and 68 can be established to be GAGCTC instead of GTGCTC.


.0164 HEMOGLOBIN M (MILWAUKEE 2)

HEMOGLOBIN M (HYDE PARK)
HEMOGLOBIN M (AKITA)
METHEMOGLOBINEMIA, BETA TYPE, INCLUDED
HBB, HIS92TYR
  
RCV000016463...

See Pisciotta et al. (1959), Heller et al. (1966), Shibata et al. (1968), and Stamatoyannopoulos et al. (1976). Rotoli et al. (1992) described the case of a cyanotic 7-year-old girl who was found to have 16% methemoglobin (617971). By molecular genetic studies, they demonstrated that this was a case of Hb M (Hyde Park). Hutt et al. (1998) showed by DNA sequence analysis that the mutation in M (Milwaukee-2), M (Hyde Park), and M (Akita) are all due to a change of codon 92 from CAC (his) to TAC (tyr).

Bird et al. (1988) reported a South African family of mixed descent in which 12 individuals with methemoglobin of the Hyde Park type also showed polyagglutination of the red cells. The 40-year-old proband had mild cyanosis and splenomegaly. The characteristics of this form of polyagglutination syndrome had not previously been reported. Red cells did not agglutinate with Arachis hypogea, Dolichos biflorus, or Salvia sclarea, but did show weak agglutination with Salvia horminum and BSII (GSII), and reacted strongly with Glycine soja and Sophora japonica lectins. BSI (GSI) lectin agglutinated group A but not group O cells. Bird et al. (1988) concluded that it was unlikely that this association between polyagglutination and the variant hemoglobin resulted from a single genetic mutation. Rather, the association may have been due to red cell denaturation and abnormal bond formation between this hemoglobin and alpha-sialoglycoprotein molecules in red blood cells.


.0165 HEMOGLOBIN M (SASKATOON)

HEMOGLOBIN M (ARHUS)
HEMOGLOBIN M (CHICAGO)
HEMOGLOBIN M (EMORY)
HEMOGLOBIN M (ERLANGEN)
HEMOGLOBIN M (HAMBURG)
HEMOGLOBIN M (HIDA)
HEMOGLOBIN M (HORLEIN-WEBER)
HEMOGLOBIN M (KURUME)
HEMOGLOBIN M (LEIPZIG)
HEMOGLOBIN M (NOVI SAD)
HEMOGLOBIN M (RADOM) METHEMOGLOBINEMIA, BETA TYPE, INCLUDED
HBB, HIS63TYR
  
RCV000016466...

This was the abnormal hemoglobin in the family with autosomal dominant cyanosis (617971) reported by Baltzan and Sugarman (1950). See Horlein and Weber (1948), Heck and Wolf (1958), Gerald and George (1959), Gerald and Efron (1961), Shibata et al. (1961, 1965), Heller (1962), Josephson et al. (1962), Hanada et al. (1964), Murawski et al. (1965), Hobolth (1965), Betke et al. (1966), Efremov et al. (1974), Kohne et al. (1975), and Baine et al. (1980). Suryantoro et al. (1995) described the his63-to-tyr mutation in an Indonesian boy with methemoglobinemia and mild hemolysis. The mutation was inherited from the mother. The report further demonstrated the worldwide distribution of Hb M-Saskatoon.


.0166 HEMOGLOBIN MACHIDA

HBB, GLU6GLN
  
RCV000016448

.0167 HEMOGLOBIN MADRID

HBB, ALA115PRO
  
RCV000016478

The hemoglobin Madrid variant was first discovered by Outeirino et al. (1974) in a Spanish patient whose parents did not carry the abnormality. A second case was observed in an American black teenager by Molchanova et al. (1993); although there was a family history of chronic hemolytic anemia, none of the family members was available for evaluation. Kim et al. (2000) described Hb Madrid in a Korean family with chronic hemolytic anemia. The amino acid substitution was due to a change at codon 115 from GCC (ala) to CCC (pro).


.0168 HEMOGLOBIN MALAY

BETA-PLUS-THALASSEMIA
BETA-MALAY-THALASSEMIA
HBB, ASN19SER
  
RCV000016479...

Yang et al. (1989) found an A-to-G change in codon 19 resulting in beta-plus-thalassemia (613985) in a Malaysian.


.0169 HEMOGLOBIN MALMO

ERYTHROCYTOSIS 6, INCLUDED
HBB, HIS97GLN
  
RCV000016482...

See Lorkin and Lehmann (1970), Fairbanks et al. (1971), Boyer et al. (1972), Berglund (1972), and Berglund and Linell (1972).

Landin et al. (1996) found this hemoglobin variant with increased oxygen affinity causing erythrocytosis in 2 apparently unrelated Swedish families. In 1 family, the his97-to-gln substitution was caused by a change from CAC-to-CAA; in the other family a CAC-to-CAG change was found.


.0170 HEMOGLOBIN MAPUTO

HBB, ASP47TYR
  
RCV000016483

.0171 HEMOGLOBIN MARSEILLE

HEMOGLOBIN LONG ISLAND
HBB, NH2 EXTENSION, HIS2PRO
  
RCV000016485

In this abnormal hemoglobin, found by isoelectric focusing in a hematologically normal though diabetic Maltese woman living in Marseille, Blouquit et al. (1984, 1985) demonstrated a double abnormality: a methionyl residue extending the NH2 terminus. This is an example of the increasing number of hemoglobin variants detected in the course of HbA1c evaluation in diabetics. Without DNA data, the authors concluded that proline in position 2 constitutes a steric impairment to the methionyl peptidase that normally eliminates the initiating methionine. The same hypothesis has been invoked to explain the apparent persistence of the initiator methionyl residue in naturally occurring proteins with a met-X sequence at the NH2-terminus, X being either a charged amino acid or a proline. Initial sequence, with abnormal residues in parentheses, equals H2N-(met)-val-(pro)-leu-thr-glu-glu-. Prchal et al. (1986) showed that the only lesion in DNA is an adenine-to-cytosine transversion in the second codon. Also see Barwick et al. (1985). Boi et al. (1989) detected this variant in Australia in the course of monitoring glycated hemoglobin (HbA1c) in diabetics. It causes a discrepancy between the HbA1c measurement and the clinical state of the diabetic patient.


.0172 HEMOGLOBIN MASUDA

HBB, LEU114MET AND GLY119ASP
  
RCV000016336...

.0173 HEMOGLOBIN MATERA

HBB, MET55LYS
  
RCV000016487

Sciarratta and Ivaldi (1990) discovered this electrophoretically slow-moving variant in an Italian family. Numerous red cells contained inclusion bodies, and heat and isopropanol tests demonstrated decreased stability of the hemoglobin.


.0174 HEMOGLOBIN MEQUON

HBB, PHE41TYR
  
RCV000016488

.0175 HEMOGLOBIN MCKEES ROCKS

ERYTHROCYTOSIS 6, INCLUDED
HBB, TYR145TER
  
RCV000016489...

The beta chain is only 144 amino acids long. The codon for beta 145 tyr has been changed to a terminator. Polycythemia is the clinical manifestation. See Winslow et al. (1975) and Rahbar et al. (1983).


.0176 HEMOGLOBIN MINNEAPOLIS-LAOS

HBB, PHE118TYR
  
RCV000016490

.0177 HEMOGLOBIN MISSISSIPPI

HEMOGLOBIN MS
HBB, SER44CYS
  
RCV000016491...

See Adams et al. (1985). Hemoglobin Mississippi has anomalous properties that include disulfide linkages with normal beta-, delta-, gamma-, and alpha-chains, and the formation of high molecular weight multimers. Heterozygotes for Hb MS are clinically and hematologically normal and heterozygotes for the beta-plus-thalassemia gene have mild microcytic anemia; however, the proband in the family initially discovered by Steinberg et al. (1987) had all the hematologic features of thalassemia intermedia in the compound heterozygous state. Steinberg et al. (1987) suggested that the unexpectedly severe clinical expression in the mixed heterozygote, as they called the state, may result from the proteolytic digestion of Hb MS as well as the excessive alpha-chains characteristic of beta-plus-thalassemia.


.0178 HEMOGLOBIN MITO

HBB, LYS144GLU
  
RCV000016493

.0179 HEMOGLOBIN MIYADA

HBB/HBD ANTI-LEPORE
HBB, HBB/HBD FUSION
   RCV000016494...

This is a beta-delta fusion variant, the complement of hemoglobin Lepore. For explanation, see hemoglobin P (Congo) (141900.0214). From a DNA sequence analysis of the Hb Miyada gene, Kimura et al. (1984) concluded that the shift from the 5-prime beta-globin gene to the 3-prime delta-globin gene occurred somewhere in a homologous sequence region between the third nucleotide of codon 17 and the second nucleotide of codon 21 of these 2 genes.


.0180 HEMOGLOBIN MIYASHIRO

HBB, VAL23GLY
  
RCV000016496

.0181 HEMOGLOBIN MIZUHO

HBB, LEU68PRO
  
RCV000016497...

See Ohba et al. (1977). Keeling et al. (1991) observed this variant in a Caucasian boy from Kentucky.

As noted by Harthoorn-Lasthuizen et al. (1995), Hb Mizuho is one of the more markedly unstable hemoglobin variants and is difficult to detect both by protein analysis and by sequencing of the amplified beta chain. The instability is due to the introduction of a proline residue in helix E, of which 5 residues form part of the heme contact. Harthoorn-Lasthuizen et al. (1995) identified a fourth case in a Dutch boy.


.0182 HEMOGLOBIN MIZUNAMI

HBB, PHE83SER
  
RCV000016498

.0183 HEMOGLOBIN MOBILE

HBB, ASP73VAL
  
RCV000016499

.0184 HEMOGLOBIN MORIGUCHI

HBB, HIS97TYR
  
RCV000016500

.0185 HEMOGLOBIN MOSCVA

HBB, GLY24ASP
  
RCV000016501

.0186 HEMOGLOBIN MOZHAISK

HBB, HIS92ARG
  
RCV000016502

.0187 HEMOGLOBIN N, BETA TYPE

HBB, LYS95ASP
   RCV000016503

.0188 HEMOGLOBIN N (BALTIMORE)

HEMOGLOBIN N (JENKINS)
HEMOGLOBIN JENKINS
HEMOGLOBIN HOPKINS 1
HEMOGLOBIN KENWOOD
HBB, LYS95GLU
  
RCV000016251...

See Clegg et al. (1965), Dobbs et al. (1966), Gottlieb et al. (1967), Ballas and Park (1985), and Anderson Fernandes (1989). In heterozygotes the concentration of Hb N (Baltimore) is the same as that of HbA. Hemoglobin Kenwood was previously reported incorrectly as having either aspartic acid or glutamic acid at beta 143. See personal communication from Heller in Hamilton et al. (1969).


.0189 HEMOGLOBIN N (MEMPHIS)

HBB, LYS95GLX
   RCV000016509

.0190 HEMOGLOBIN N (SEATTLE)

HBB, LYS61GLU
  
RCV000016510...

.0191 HEMOGLOBIN N (TIMONE)

HBB, LYS8GLU
  
RCV000016511...

.0192 HEMOGLOBIN NAGASAKI

HBB, LYS17GLU
  
RCV000016512

See Maekawa et al. (1970). Nakamura et al. (1997) identified a second case in a Japanese family. The proband was a 47-year-old diabetic male. The anomaly was identified during the HPLC assay for HBA1c. The abnormal beta chain comprised about 44% of the total beta chain as opposed to 30% in the previous report.


.0193 HEMOGLOBIN NAGOYA

HBB, HIS97PRO
  
RCV000016513

Hb Nagoya is an unstable hemoglobin found in father and son in Japan (Ohba et al., 1985).


.0194 HEMOGLOBIN NEVERS

HBB, TYR130SER
  
RCV000016514

During an investigation for erythrocytosis, Keclard et al. (1990) found this electrophoretically silent beta chain variant in a French-Caucasian male. The sister, mother, and grandmother carried the same abnormal hemoglobin in heterozygous state. The mother showed mild erythrocytosis.


.0195 HEMOGLOBIN NEW MEXICO

HBB, PRO100ARG
  
RCV000016515...

.0196 HEMOGLOBIN NEW YORK

HEMOGLOBIN KAOHSIUNG
HBB, VAL113GLU
  
RCV000016516...

This variant was found in a Chinese-American family. See Ranney et al. (1967), Kendall and Pang (1980), Saenz et al. (1980), and Todd et al. (1980).


.0197 HEMOGLOBIN NEWCASTLE

HBB, HIS92PRO
  
RCV000016518...

.0198 HEMOGLOBIN NITEROI

HBB, PHE42DEL, GLU43DEL, SER44DEL
  
RCV000016519

Deletion of phenylalanine, glutamic acid and serine at either beta 42-44 or beta 43-45. See Praxedes et al. (1972).


.0199 HEMOGLOBIN NORTH CHICAGO

HBB, PRO36SER
  
RCV000016520

Increased oxygen affinity. Discovered in a 52-year-old man treated since age 20 years for polycythemia vera with various measures including several courses of 32(P) (Rahbar et al., 1985).


.0200 HEMOGLOBIN NORTH SHORE

HEMOGLOBIN NORTH SHORE-CARACAS
HBB, VAL134GLU
  
RCV000016521

.0201 HEMOGLOBIN NOTTINGHAM

HBB, VAL98GLY
  
RCV000016523

See Gordon-Smith et al. (1973) and Orringer et al. (1978). The patient of Orringer et al. (1978) was a 7-year-old boy with severe hemolytic anemia in whom great improvement in clinical status, including rate of growth, was noted 1 year after he underwent a splenectomy and cholecystectomy. Cepreganova et al. (1992) described severe hemolytic anemia in a 7-year-old Canadian boy with Hb Nottingham. Brabec et al. (1994) reported a fourth case in an 8-year-old girl in the Czech Republic with severe hemolytic anemia.


.0202 HEMOGLOBIN O (ARAB)

HEMOGLOBIN EGYPT
HBB, GLU121LYS
  
RCV000016524...

This hemoglobin has been found in American blacks, Bulgarians, and Arabs (Kamel et al., 1967). Little et al. (1980) illustrated the fact that point mutation can be recognized by the change in susceptibility to cleavage by specific restriction endonucleases. The examples were: Hb O(Arab) with EcoRI, Hb J(Broussais) with HindIII, and Hb F(Hull) with EcoRI. The sickle cell mutation eliminates a site for MnlI. See Ramot et al. (1960), Kamel et al. (1967), Vella et al. (1966), Milner et al. (1970), and Charache et al. (1977).


.0203 HEMOGLOBIN OCHO RIOS

HBB, ASP52ALA
  
RCV000016526

.0204 HEMOGLOBIN OHIO

ERYTHROCYTOSIS 6, INCLUDED
HBB, ALA142ASP
  
RCV000016527...

High oxygen affinity leads to erythrocytosis. See Moo-Penn et al. (1980).


.0205 HEMOGLOBIN OKALOOSA

HBB, LEU48ARG
  
RCV000016528

.0206 HEMOGLOBIN OKAYAMA

HBB, HIS2GLN
  
RCV000016529...

.0207 HEMOGLOBIN OKAZAKI

HBB, CYS93ARG
  
RCV000016530...

.0208 HEMOGLOBIN OLMSTED

HBB, LEU141ARG
  
RCV000016531...

See Fairbanks et al. (1969) and Lorkin and Lehmann (1970). Thuret et al. (1996) described a second case of this unstable hemoglobin. The clinical course of a 12-year-old boy was characterized by severe hemolytic anemia leading to splenectomy and cholecystectomy at the age of 3.5 years. Priapism occurred 8 years after splenectomy, during a hemolytic febrile episode, and required aspiration of the corpora cavernosa. Splenectomy in cases of chronic hemolytic anemia due to an unstable hemoglobin lowers the frequency and severity of acute hemolytic attacks but vascular complications often occur. The original patient with Hb Olmsted, described by Fairbanks et al. (1969) died of chronic pulmonary disease with pulmonary hypertension at age 36 years. The patient reported by Thuret et al. (1996) had a French mother and Spanish father.


.0209 HEMOGLOBIN OLOMOUC

HBB, ALA86ASP
  
RCV000016532

This beta-chain variant, associated with erythrocytosis, was first discovered in a member of a Czechoslovakian family (Indrak et al., 1987). Tagawa et al. (1992) found the same mutation in a Japanese family.


.0210 HEMOGLOBIN OLYMPIA

ERYTHROCYTOSIS 6, INCLUDED
HBB, VAL20MET
  
RCV000016533...

Since GUG to AUG is the only single base change that can result in this substitution, the codon for beta 20 can be uniquely identified as GUG. See Stamatoyannopoulos et al. (1973) and Weaver et al. (1984). Berlin and Wranne (1989) described hemoglobin Olympia in a Swedish family.


.0211 HEMOGLOBIN OSLER

HEMOGLOBIN NANCY
HEMOGLOBIN FORT GORDON
ERYTHROCYTOSIS 6, INCLUDED
HBB, TYR145ASN-TO-ASP
  
RCV000781441...

Compensatory erythrocytosis results from its high oxygen affinity. See Charache et al. (1975), Gacon et al. (1975), Kleckner et al. (1975), and Butler et al. (1982).

Kattamis et al. (1997) found hemoglobin Osler in 2 members of an African American family with erythrocytosis. Sequence analysis of DNA from the proband showed heterozygosity for a T-to-A transversion at the first position of codon 145 in the HBB gene, which resulted in the substitution of an asparagine for normal tyrosine. The second cycle of C-terminal amino acid sequence analysis of a mixture of alpha- and beta-globin chains showed tyrosine, aspartic acid, and small amounts of asparagine. Collectively, these results were interpreted as indicating the existence of a mutation at codon 145 of the HBB gene, which codes for asparagine instead of tyrosine, and that asparagine then undergoes initial posttranslational deamidation to aspartic acid. Thus the mutation is tyr145asn, not tyr145asp, as initially thought. Posttranslational modifications had been described in 4 other beta-globin chains and 2 alpha-globin chain variants: Hb Providence (141900.0227), Hb Redondo, or Isehara (141900.0404), Hb La Roche-sur-Yon (141900.0482), Hb J (Singapore) (141800.0075), Hb Wayne (141850.0004), and the only variant in which the posttranslational modification does not involve an asn-to-asp substitution, Hb Bristol (val167met-asp; 141900.0030).


.0212 HEMOGLOBIN OSU CHRISTIANSBORG

HBB, ASP52ASN
  
RCV000016537...

Konotey-Ahulu et al. (1971) first observed this nonpathologic mutant in a Ghanaian patient with Hb S (141900.0243). By molecular analysis of the HBB gene, Giordano et al. (1999) identified the same mutant in 2 unrelated families of African origin living in the Netherlands, one from Ghana and the other from the Dominican Republic. In all carriers of both families, the mutation was associated with haplotype 11, an infrequent haplotype in the West African population, suggesting a single common mutation event. Giordano et al. (1999) stated that because Hb Osu-Christiansborg migrates at a similar rate to that of Hb S in alkaline hemoglobin electrophoresis, it can easily be mistaken for Hb S.

Hb Osu-Christiansborg has been described in several parts of the world and the mutation is believed to have had independent origins in these cases. Rodrigues de Souza et al. (2004) reported the first case of Hb Osu-Christiansborg in Brazil. The patient was a healthy 10-year-old boy, descendant of Spanish and Brazilian Native Indians. Hematologic data were all normal. The mutation was not found in the parents. Paternity testing confirmed the biologic relationship between the parents and the child, demonstrating that this was a de novo mutation.


.0213 HEMOGLOBIN P

HEMOGLOBIN P (GALVESTON)
HBB, HIS117ARG
  
RCV000016538...

.0214 HEMOGLOBIN P (CONGO)

HBB/HBD ANTI-LEPORE
HBB, HBB/HBD FUSION
   RCV000016540

This is a beta-delta fusion variant, the complement of hemoglobin Lepore. Unlike the delta-beta fusion product of Lepore hemoglobin, the non-alpha chain resembles beta at the NH2-end. Furthermore, HbA2 is present in normal concentrations and both HbA and HbS (or other beta variant) can be present in the patient heterozygous for hemoglobin P (Congo). The explanation for the origin of hemoglobin Lepore and hemoglobin P (Congo) (nonhomologous pairing and unequal crossing-over) is diagrammed in Fig. 2.20 (p. 41) of McKusick (1969). The fusion occurs between beta 22 and delta 116 (Lehmann and Charlesworth, 1970). See Dherte et al. (1959), Lehmann et al. (1964), Lambotte-Legrand et al. (1960), and Gammack et al. (1961).


.0215 HEMOGLOBIN P (NILOTIC)

HBB/HBD ANTI-LEPORE
HBB, HBB/HBD FUSION
   RCV000016542...

This is a beta-delta fusion product like Hb P (Congo) and Hb Miyada. The fusion site is beta 22 to delta 50. Thus, Hb P(Nilotic) is identical to Hb Lincoln Park (141900.0157) except for deletion of delta residue 137 in Hb Lincoln Park. Thus, it is the complement of Hb Lepore (Hollandia). See Badr et al. (1973). Among 8 chromosomes carrying the Hb P (Nilotic) hybrid gene, Lanclos et al. (1987) found only 1 haplotype.


.0216 HEMOGLOBIN PALMERSTON NORTH

ERYTHROCYTOSIS 6, INCLUDED
HBB, VAL23PHE
  
RCV000016544...

.0217 HEMOGLOBIN PASADENA

HBB, LEU75ARG
  
RCV000016545

.0218 HEMOGLOBIN PERTH

HEMOGLOBIN ABRAHAM LINCOLN
HEMOGLOBIN KOBE
HBB, LEU32PRO
  
RCV000016546...

This is an unstable hemoglobin resulting in hemolytic anemia. See Jackson et al. (1973), Honig et al. (1973), Rousseaux et al. (1980), and Shibata et al. (1980).


.0219 HEMOGLOBIN PETERBOROUGH

HBB, VAL111PHE
  
RCV000016549

See King et al. (1972).

Nakanishi et al. (1998) provided the second report of Hb Peterborough and the first of its occurrence in Japan.


.0220 HEMOGLOBIN PHILLY

HBB, TYR35PHE
  
RCV000016550

An unstable hemoglobin leading to hemolytic anemia. No electrophoretic abnormality. See Rieder et al. (1969) and Asakura et al. (1981).


.0221 HEMOGLOBIN PIERRE-BENITE

HBB, GLU90ASP
  
RCV000016551...

.0222 HEMOGLOBIN PITIE-SALPETRIERE

ERYTHROCYTOSIS 6, INCLUDED
HBB, VAL34PHE
  
RCV000016552...

Associated with erythrocytosis. See Blouquit et al. (1980).


.0223 HEMOGLOBIN POISSY

HBB, GLY56ARG AND ALA86PRO
  
RCV000016369...

.0224 HEMOGLOBIN PORTO ALEGRE

HBB, SER9CYS
  
RCV000016556...

This hemoglobin has an extra reactive thiol group because of the substitution of cysteine for serine. Octamers and dodecamers form in hemolysates of heterozygotes and homozygotes, respectively, on standing, through linkage between tetramers by disulfide bridges. See Tondo et al. (1963), Bonaventura and Riggs (1967), Seid-Akhavan et al. (1973), and Tondo (1976).

Salzano (2000) tabulated the Hbb variants observed in Latin America and provided further information on Hb Porto Alegre, which had been discovered by his group in a family of Portuguese descent living in the Brazilian city of that name. Substitution of cysteine for serine at the ninth residue of the chain created a sulfhydryl group on the surface of the molecule, allowing formation of intermolecular disulfide bonds. However, polymerization occurs in vitro but not in vivo, and the variant hemoglobin leads to no clinical problems. Lack of polymerization in vivo may be because of a compensatory synthesis of glutathione reductase.


.0225 HEMOGLOBIN POTOMAC

ERYTHROCYTOSIS 6, INCLUDED
HBB, GLU101ASP
  
RCV000016557...

.0226 HEMOGLOBIN PRESBYTERIAN

HBB, ASN108LYS
  
RCV000016558

See Moo-Penn et al. (1978), Horst et al. (1983), and Villegas et al. (1986). Using PCR and direct sequencing, Schnee et al. (1990) demonstrated that the molecular defect is a C-to-G substitution in codon 108; this eliminates an MaeII restriction site.

The beta variant lys108 enhances the stability of hemoglobin in the deoxy-state, conferring low affinity for oxygen binding in vitro. Suzuki et al. (2002) generated mutant mice carrying the Presbyterian mutation at the beta-globin locus by a targeted knockin strategy. Heterozygous mice showed the expression of Hb Presbyterian in 27.7% of total peripheral blood without any hematologic abnormalities, which well mimicked human cases. On the other hand, homozygous mice exclusively expressed Hb Presbyterian in 100% of peripheral blood associated with hemolytic anemia, Heinz body formation, and splenomegaly. Hb Presbyterian showed instability in an in vitro precipitation assay. Erythrocytes from homozygous mice showed a shortened life span when transfused into wildtype mice, confirming that the knocked-in mutation of lys108 caused hemolysis in homozygous mice. Suzuki et al. (2002) stated that this was the first report on the hemolytic anemia of unstable hemoglobin in an animal model. The results confirmed the notion that the higher ratio of an unstable variant beta-globin chain in erythrocytes triggers the pathologic precipitation and induces hemolysis in abnormal hemoglobinopathies.


.0227 HEMOGLOBIN PROVIDENCE

ERYTHROCYTOSIS 6, INCLUDED
HBB, LYS82ASX
  
RCV000016559...

.0228 HEMOGLOBIN PYRGOS

HBB, GLY83ASP
  
RCV000016560...

See Tatsis et al. (1972) and Yamada et al. (1977). Schiliro et al. (1991) found this hemoglobin variant in a mother and son in Sicily who were both clinically and hematologically normal.


.0229 HEMOGLOBIN QUIN-HAI

HBB, LEU78ARG
  
RCV000016554

.0230 HEMOGLOBIN RADCLIFFE

ERYTHROCYTOSIS 6, INCLUDED
HBB, ASP99ALA
  
RCV000016555...

Cause of polycythemia. See Weatherall et al. (1977).


.0231 HEMOGLOBIN RAHERE

ERYTHROCYTOSIS 6, INCLUDED
HBB, LYS82THR
  
RCV000016561...

See Lorkin et al. (1975) and Sugihara et al. (1985). Beta 82 is at the binding site of 2,3-diphosphoglycerate. Hb Rahere is accompanied by erythrocytosis.


.0232 HEMOGLOBIN RAINIER

ERYTHROCYTOSIS 6, INCLUDED
HBB, TYR145CYS
  
RCV000016562...

See Stamatoyannopoulos et al. (1968), Adamson et al. (1969), Stamatoyannopoulos and Yoshida (1969), Greer and Perutz (1971), Hayashi et al. (1971), and Salhany (1972). Hb Rainier causes erythrocytosis and is the only adult hemoglobin that is alkali-resistant. See Hb Bethesda (141900.0022), with which Rainier was confused earlier. Peters et al. (1985) studied a hemoglobin mutation induced by ethylnitrosourea in the mouse. Substitution of cysteine for tyrosine at codon 145 of the HBB gene was demonstrated by amino acid analysis. They proposed that an A-to-G transition in the tyrosine codon (TAC-to-TGC) had occurred. The mouse was polycythemic.

Carbone et al. (1999) identified a high oxygen affinity hemoglobin variant in a 53-year-old male from Naples, Italy, who suffered from pulmonary thromboembolism and polycythemia. Characterization of this variant at the protein level detected the presence of Hb Rainier. The mutation resulted from an A-to-G transition at the second position of codon 145 of the HBB gene, resulting in a tyr145-to-cys substitution.


.0233 HEMOGLOBIN RALEIGH

HBB, VAL1ALA
  
RCV000016563...

Substitution of acetylalanine for valine at beta 1. See Moo-Penn et al. (1977).

This variant was numbered based on the first amino acid of the mature protein. In the gene-based system of counting, this variant is VAL2ALA.


.0234 HEMOGLOBIN RANDWICK

HBB, TRP15GLY
  
RCV000016564

.0235 HEMOGLOBIN REGINA

HBB, LEU96VAL
  
RCV000016565

See Devaraj et al. (1985). Bisse et al. (1991) reported the second affected family. The hemoglobin variant was associated with high oxygen affinity and erythrocytosis.


.0236 HEMOGLOBIN RICHMOND

HBB, ASN102LYS
  
RCV000016566

.0237 HEMOGLOBIN RIO GRANDE

HBB, LYS8THR
  
RCV000030668

.0238 HEMOGLOBIN RIVERDALE-BRONX

HBB, GLY24ARG
  
RCV000016567

.0239 HEMOGLOBIN RIYADH

HEMOGLOBIN KARATSU
HBB, LYS120ASN
  
RCV000016568...

.0240 HEMOGLOBIN ROSEAU-POINTE A PITRE

HBB, GLU90GLY
  
RCV000016570

.0241 HEMOGLOBIN ROTHSCHILD

HBB, TRP37ARG
  
RCV000016571

See Gacon et al. (1977) and Danish et al. (1982). Kavanaugh et al. (1992) reported x-ray crystallographic studies.


.0242 HEMOGLOBIN RUSH

HBB, GLU101GLN
  
RCV000016572

.0243 HEMOGLOBIN S

SICKLE CELL DISEASE, INCLUDED
MALARIA, RESISTANCE TO, INCLUDED
HBB, GLU6VAL
   RCV000016286...

The change from glutamic acid to valine in sickle hemoglobin was reported by Ingram (1959). Ingram (1956) had reported that the difference between hemoglobin A and hemoglobin S lies in a single tryptic peptide. His analysis of this peptide, peptide 4, was possible by the methods developed by Sanger for determining the structure of insulin and Edman's stepwise degradation of peptides.

Kan and Dozy (1978) used the HpaI restriction endonuclease polymorphism (actually the linkage principle) to make the prenatal diagnosis of sickle cell anemia (603903). As described in 143020, when 'normal' DNA is digested with HpaI, the beta-globin gene is contained in a fragment 7.6 kilobases long. In persons of African extraction 2 variants were detected, 7.0 kb and 13.0 kb long. These variants resulted from alteration in the normal HpaI recognition site 5000 nucleotides to the 3-prime side of the beta-globin gene. The 7.6 and 7.0 kb fragments were present in persons with Hb A, while 87% of persons with Hb S had the 13.0 kb variant. The method is sufficiently sensitive that the cells in 15 ml of uncultured amniotic fluid sufficed. Restriction enzyme studies indicate that whereas Hb S and Hb C originated against the same genetic background (as independent mutations) and the Hb S in the Mediterranean littoral probably is the same mutation as the West African Hb S, Hb S in Asia is apparently a separate mutation. It does not show association with the noncoding polymorphism (Kan and Dozy, 1979).

Mears et al. (1981) used the linkage of the sickle gene with restriction polymorphisms to trace the origin of the sickle gene in Africa. They found evidence that 2 different chromosomes bearing sickle genes were subjected to selection and expansion in 2 physically close but ethnically separate regions of West Africa, with subsequent diffusion to other areas of Africa. The restriction enzyme MnlI recognizes the sequence G-A-G-G, which also is eliminated by the sickle mutation. The MstII enzyme recognizes the sequence C-C-T-N-A-G-G. Predictably, the resulting fragments are larger than those produced by some other enzymes, and MstII is, therefore, particularly useful in prenatal diagnosis (Wilson et al., 1982). The sickle cell mutation can be identified directly in DNA by use of either of 2 restriction endonucleases, DdeI or MstII (Geever et al., 1981; Kazazian, 1982). The nucleotide substitution alters a specific cleavage site recognized by each of these 2 enzymes. The fifth, sixth, and seventh codons of Hb A are CCT-GAG-GAG; in Hb S, they are CCT-GTG-GAG. The recognition site for DdeI is C-T-N-A-G, in which N = any nucleoside. Chang and Kan (1982) and Orkin et al. (1982) found that the assay using the restriction enzyme MstII is sufficiently sensitive that it can be applied to uncultured amniotic fluid cells. The enzyme DdeI requires that the amniotic cells be cultured to obtain enough DNA for the assay.

Antonarakis et al. (1984) applied the Kazazian haplotype method to the study of the origin of the sickle mutation in Africans. Among 170 beta-S bearing chromosomes, 16 different haplotypes of polymorphic sites were found. The 3 most common beta-S haplotypes, accounting for 151 of the 170, were only rarely seen in chromosomes bearing the beta-A gene in these populations (6 out of 47). They suggested the occurrence of up to 4 independent mutations and/or interallelic gene conversions. By haplotype analysis of the beta-globin gene cluster in cases of Hb S in different parts of Africa, Pagnier et al. (1984) concluded that the sickle mutation arose at least 3 times on separate preexisting chromosomal haplotypes. The Hb S gene is closely linked to 3 different haplotypes of polymorphic endonuclease restriction sites in the beta-like gene cluster: one prevalent in Atlantic West Africa, another in central West Africa, and the last in Bantu-speaking Africa (equatorial, East, and southern Africa). Nagel et al. (1985) found hematologic differences between the first 2 types explicable probably by differences in fetal hemoglobin production. Ramsay and Jenkins (1987) found that 20 of 23 sickle-associated haplotypes in southern-African Bantu-speaking black subjects were the same as those found commonly in the Central African Republic, a finding providing the first convincing biologic evidence for the common ancestry of geographically widely separated speakers of languages belonging to the Bantu family. The 3 haplotypes seen with the beta-S gene in Africa are referred to as Senegal, Benin, and Bantu. The 'Bantu line' extends across the waist of Africa; south of the line, Bantu languages are spoken. Based on their study, Ramsay and Jenkins (1987) suggested that the sickle cell mutation arose only once in the Bantu speakers, presumably in their nuclear area of origin, before the Bantu expansion occurred about 2,000 years ago. In Yaounde, the capital city of Cameroon, Lapoumeroulie et al. (1992) observed a novel RFLP pattern in the study of beta-S chromosomes. This chromosome contained an A-gamma-T gene and the RFLP haplotype was different from all the other beta(S) chromosomes in both the 5-prime and 3-prime regions. All the carriers of this specific chromosome belonged to the Eton ethnic group and originated from the Sanaga river valley.

Kulozik et al. (1986) found that the sickle gene in Saudi Arabia and on the west and east coasts of India exists in a haplotype not found in Africa. They concluded that the data are most consistent with an independent Asian origin of the sickle cell mutation. The distribution of the Asian beta-S-haplotype corresponded to the reported geographic distribution of a mild clinical phenotype of homozygous SS disease. Ragusa et al. (1988) found that the beta-S gene in Sicily is in linkage disequilibrium with the Benin haplotype, the same haplotype observed among sickle cell anemia patients from Central West Africa. In addition, this haplotype is either nonexistent or very rare among nonsickling Sicilian persons. They concluded that the beta-S gene was introduced into Sicily from North Africa and that the gene flow originated in Central West Africa, traveling north through historically well-defined trans-Saharan commercial routes.

Zeng et al. (1994) indicated that 5 different haplotypes associated with Hb S had been described, 4 in Africa (Bantu, Benin, Senegal, and Cameroon) and 1 found in both India and Saudi Arabia (Chebloune et al., 1988). There is a correlation between disease severity and haplotype for at least the 2 extremes of severity: patients with the Indian/Arabian haplotype have the mildest course of disease, while those with the Bantu haplotype exhibit the most severe course. Nucleotide -530 is a binding site for a protein called BP1 (601911), which may be a repressor of the HBB gene. BP1 binds with the highest affinity to the Indian haplotype sequence and with the weakest affinity to the Bantu sequence, which might explain the differences in clinical course in these different population groups. Zeng et al. (1994) demonstrated the same sequence at -530 bp in patients with the Arabian haplotype as in Indian sickle cell anemia patients. This supports the idea of a common origin of the sickle cell mutation in individuals in India and Saudi Arabia.

Sammarco et al. (1988) presented further strong evidence that the Hb S gene in Sicily was brought by North African populations, probably during the Muslim invasions.

Currat et al. (2002) studied the genetic diversity of the beta-globin gene cluster in an ethnically well-defined population, the Mandenka from eastern Senegal. The absence of recent admixture and amalgamation in this population permitted application of population genetics methods to investigate the origin of the sickle cell mutation (Flint et al., 1993) and to estimate its age. The frequency of the sickle cell mutation in the Mandenka was estimated as 11.7%. The mutation was found strictly associated with the single Senegal haplotype. Approximately 600 bp of the upstream region of the beta-globin gene were sequenced for 94 chromosomes, showing the presence of 4 transversions, 5 transitions, and a composite microsatellite polymorphism. The sequence of 22 chromosomes carrying the sickle mutation was also identical to the previously defined Senegal haplotype, suggesting that the mutation is very recent. Maximum likelihood estimates of the age of the mutation using Monte Carlo simulations were 45 to 70 generations (1,350-2,100 years) for different demographic scenarios.

Embury et al. (1987) described a new method for rapid prenatal diagnosis of sickle cell anemia by DNA analysis. The first step involved a 200,000-fold enzymatic amplification of the specific beta-globin DNA sequences suspected of carrying the sickle mutation. Next, a short radiolabelled synthetic DNA sequence homologous to normal beta-A-globin gene sequences is hybridized to the amplified target sequence. The hybrid duplexes are then digested sequentially with 2 restriction endonucleases. The presence of the beta-A or beta-S gene sequence in the amplified target DNA from the patient determines whether the beta-A hybridization probe anneals perfectly or with a single nucleotide mismatch. This difference affects the restriction enzyme digestion of the DNA and the size of the resulting radiolabelled digestion products which can be distinguished by electrophoresis followed by autoradiography. The method was sufficiently sensitive and rapid that same-day prenatal diagnosis using fetal DNA was possible. The same test could be applied to the diagnosis of hemoglobin C disease. Hemoglobin C (Georgetown) also sickles. See Herrick (1910), Sherman (1940), Neel (1949), Pauling et al. (1949), Allison (1954), Ingram (1956, 1957, 1959), Chang and Kan (1981), and Shalev et al. (1988).

Barany (1991) described a new assay designed to detect single base substitutions using a thermostable enzyme similar to the DNA polymerase used in PCR. This enzyme, DNA ligase, specifically links adjacent oligonucleotides only when the nucleotides are perfectly base-paired at the junction. In the presence of a second set of adjacent oligonucleotides, complementary to the first set and the target, the oligonucleotide products may be exponentially amplified by thermal cycling of the ligation reaction. Because a single base mismatch precludes ligation and amplification, it will be easily distinguished. Barany (1991) demonstrated the utility of the method in discriminating between normal and sickle globin genotypes from 10 microliter blood samples.

Prezant and Fischel-Ghodsian (1992) described a trapped-oligonucleotide nucleotide incorporation (TONI) assay for the screening of a mitochondrial polymorphism and also showed that it could distinguish the genotypes of hemoglobins A/C, A/A, A/S, and S/S. The method was considered particularly useful for diagnosing mutations that do not produce alterations detectable by restriction enzyme analysis. It also requires only a single oligonucleotide and no electrophoretic separation of the allele-specific products. It represents an improved and simplified modification of the allele-specific primer extension methods. (TONI, the acronym for the method, is also the given name of the first author.)

Grosveld et al. (1987) identified dominant control region (DCR) sequences that flank the human beta-globin locus and direct high-level, copy-number-dependent expression of the human beta-globin gene in erythroid cells in transgenic mice. By inserting a construct that included 2 human alpha genes and the defective human beta-sickle gene, all driven by the DCR sequences, Greaves et al. (1990) produced 2 mice with relatively high levels of human Hb S in their red cells. Use of this as an animal model for the study of this disease was suggested.

Turhan et al. (2002) presented evidence suggesting that a pathogenetic mechanism in sickle cell vasoocclusion may reside in adherent leukocytes. Using intravital microscopy in mice expressing human sickle hemoglobin, they demonstrated that SS red blood cells bind to adherent leukocytes in inflamed venules, producing vasoocclusion of cremasteric venules. SS mice deficient in P- and E-selectins, which display defective leukocyte recruitment to the vessel wall, were protected from vasoocclusion. Thus, drugs targeting SS RBC-leukocyte or leukocyte-endothelial interactions might prevent or treat the vascular complications of this disease.

Nitric oxide (NO), essential for maintaining vascular tone, is produced from arginine by NO synthase. Plasma arginine levels are low in sickle cell anemia, and Romero et al. (2002) reported that the sickle transgenic mouse model has low plasma arginine. They supplemented these mice with a 4-fold increase in arginine over a period of several months. Mean corpuscular hemoglobin concentration decreased and the percent high-density red cells was reduced. Romero et al. (2002) concluded that the major mechanism by which arginine supplementation reduces red cell density in these mice is by inhibiting the Ca(++)-activated K(+) channel.

In a Jamaican study, Serjeant et al. (1968) described 60 patients with homozygous sickle cell disease who were 30 years of age or older, and Platt et al. (1994) estimated a median survival of 42 to 48 years. Serjeant et al. (2007) stated that the sickle cell clinic at the University of West Indies had treated 102 patients (64.7% women) who survived beyond their 60th birthday. None of the patients received hydroxyurea, and only 2 patients with renal impairment received regular transfusions. The ages of the patients ranged from 60.2 to 85.6 years. Measurement of fetal hemoglobin levels suggested that higher fetal hemoglobin levels probably conferred protection in childhood. The major clinical problems emerging with age were renal impairment and decreased levels of hemoglobin.

Kwiatkowski (2005) noted that HbS homozygotes have sickle-cell disease, whereas heterozygosity confers a 10-fold increase in protection from life-threatening malaria (611162) and lesser protection against mild malaria.

Cholera et al. (2008) found that P. falciparum (Pf)-infected HbA/HbS erythrocytes did not bind to microvascular endothelial cells as well as Pf-infected HbA/HbA erythrocytes. Reduced binding correlated with altered display of the major Pf cytoadherence ligand on erythrocyte membranes. Cholera et al. (2008) noted that this protective mechanism had features in common with that of HbC (141900.0038), and they suggested that weakening of cytoadherence interactions may influence the degree of malaria protection in HbA/HbS children.

Modiano et al. (2008) adopted 2 partially independent haplotypic approaches to study the Mossi population in Burkina Faso, where both the HbS and HbC alleles are common. They showed that both alleles are monophyletic, but that the HbC allele has acquired higher recombinatorial and DNA slippage haplotypic variability or linkage disequilibrium decay and is likely older than HbS. Modiano et al. (2008) inferred that the HbC allele has accumulated mainly through recessive rather than a semidominant mechanism of selection.

Gouagna et al. (2010) used cross-sectional surveys of 3,739 human subjects and transmission experiments involving 60 children and over 6,000 mosquitoes in Burkina Faso, West Africa, to test whether the HBB variants HbC and HbS, which are protective against malaria, are associated with transmission of the parasite from the human host to the Anopheles mosquito vector. They found that HbC and HbS were associated with significant 2-fold in vivo (P = 1.0 x 10(-6)) and 4-fold ex vivo (P = 7.0 x 10(-5)) increases of parasite transmission from host to vector. In addition, mean oocyte densities were particularly high in mosquitoes fed from HbS carriers.

Ferreira et al. (2011) demonstrated that wildtype mice or mice expressing normal human Hb, but not mice expressing Hbs, developed experimental cerebral malaria (ECM) 6 to 12 days after infection with the murine malaria parasite, Plasmodium berghei. The Hbs mice eventually succumbed to the unrelated condition of hyperparasitemia-induced anemia. Tolerance to Plasmodium infection was associated with high levels of Hmox1 (141250) expression in hematopoietic cells, and mice expressing Hbs became susceptible to ECM when Hmox1 expression was inhibited. Hbs induced expression of Hmox1 in an Nrf2 (NFE2L2; 600492)-dependent manner, which inhibited the production of chemokines and Cd8-positive T cells associated with ECM pathogenesis. Ferreira et al. (2011) concluded that sickle hemoglobin suppresses the onset of ECM via induction of HMOX1 and the production of carbon monoxide, which inhibits the accumulation of free heme, affording tolerance to Plasmodium infection.

Cyrklaff et al. (2011) found that HbS and HbC affect the trafficking system that directs parasite-encoded proteins to the surface of infected erythrocytes. Cryoelectron tomography revealed that P. falciparum generates a host-derived actin cytoskeleton within the cytoplasm of wildtype red blood cells that connects the Maurer clefts with the host cell membrane and to which transport vesicles are attached. The actin cytoskeleton and the Maurer clefts were aberrant in erythrocytes containing HbS or HbC. Hemoglobin oxidation products, enriched in HbS and HbC erythrocytes, inhibited actin polymerization in vitro and may account for the protective role in malaria.


.0244 HEMOGLOBIN S (ANTILLES)

HBB, GLU6VAL AND VAL23ILE
  
RCV000016286...

This variant has electrophoretic mobility in standard conditions identical to that of Hb S but shows a slightly higher pI than Hb S on isoelectric focusing. Heterozygous carriers of this variant hemoglobin exhibit sickling disorders. This observation may provide a clue to the unexplained clinical sickling disorders in some A/S carriers, in whom careful biochemical analyses may reveal other examples of double mutations in the beta chain. See Monplaisir et al. (1986). Pagnier et al. (1990) introduced the val23-to-ile mutation into beta-globin cDNA by site-directed mutagenesis. The beta-globin chain was synthesized using an expression vector and hemoglobin tetramers were reconstituted. When mixed with equal amounts of hemoglobin S, facilitation of polymerization was observed. Pagnier et al. (1990) listed 5 other hemoglobin variants which contain both the sickle mutation and a second amino acid substitution in the same beta chain.

Popp et al. (1997) bred 2 homozygous viable Hb S Antilles transgene insertions into a strain of mice that produce hemoglobins with a higher affinity for oxygen than normal mouse Hb. The rationale was that the high oxygen affinity hemoglobin, the lower oxygen affinity of Hb S Antilles, and the lower solubility of deoxygenated Hb Antilles than Hb S would favor deoxygenation and polymerization of human Hb S Antilles in the red cells of the high oxygen affinity mice. The investigators found that the mice produced a high and balanced expression of human alpha and human beta (S Antilles) globins, that 25 to 35% of their RBCs were misshapen in vivo, and that in vitro deoxygenation of their blood induced 30 to 50% of the RBCs to form classic elongated sickle cells with pointed ends. The mice exhibited reticulocytosis, an elevated white blood cell count, and lung and kidney pathology commonly found in sickle cell patients, which should make these mice useful for experimental studies on possible therapeutic intervention of sickle cell disease.


.0245 HEMOGLOBIN S (OMAN)

HEMOGLOBIN S/O (ARAB)
HBB, GLU6VAL AND GLU121LYS
  
RCV000016286...

Langdown et al. (1989) described a doubly substituted sickling hemoglobin with the change of glu-to-val at beta 6 (141900.0243) and glu-to-lys at beta 121 (141900.0202). The double substitution resulted in a variant with reduced solubility and apparent increase in red cell sickling tendency. Hemoglobin S (Oman) combines the classic Hb S mutation (glu6 to val), with the Hb O (Arab) mutation (glu121 to lys). Nagel et al. (1998) studied a pedigree of heterozygous carriers of Hb S (Oman) that segregated into 2 types of patients: those expressing about 20% Hb S (Oman) and concomitant -alpha/alpha-alpha thalassemia and those with about 14% of Hb S (Oman) and concomitant -alpha/-alpha thalassemia. The higher expressors of Hb S (Oman) had a sickle cell anemia clinical syndrome of moderate intensity, whereas the lower expressors had no clinical syndrome and were comparable to the solitary case first described in Oman. In addition, the higher expressors exhibited a unique form of irreversibly sickled cell reminiscent of a 'yarn and knitting needle' shape, in addition to folded and target cells. Purified Hb S (Oman) has a C(SAT) (solubility of the deoxy polymer) of 11 g/dL, much lower than Hb S alone (17.8 g/dL). Another double mutant, Hb S (Antilles) (141900.0244), has a similarly low C(SAT) and much higher expression (40 to 50%) in the trait form, but has a phenotype that is similar in intensity to the trait form of Hb S (Oman). Nagel et al. (1998) concluded that the pathology of heterozygous S (Oman) is the product of recipient properties of the classic mutation which are enhanced by the second mutation at beta-121. In addition, the syndrome is further enhanced by a hemolytic anemia induced by the beta-121 mutation. They speculated that the hemolytic anemia results from the abnormal association of the highly positively charged Hb S (Oman) (3 charges different from normal hemoglobin) with the RBC membrane.

To characterize better the clinical and laboratory aspects of Hb S (Oman), also called Hb S/O (Arab), Zimmerman et al. (1999) reviewed the Duke University Medical Center experience. They identified 13 African American children and adults with Hb S/O (Arab), ranging in age from 2.7 to 62.5 years. All patients had hemolytic anemia with a median hemoglobin of 8.7 gm/dL and a median reticulocyte count of 5.8%. The peripheral blood smear typically showed sickled erythrocytes, target cells, polychromasia, and nucleated red blood cells. All 13 patients had had significant clinical sickling events, including acute chest syndrome (11), recurrent vasoocclusive painful events (10), dactylitis (7), gallstones (5), nephropathy (4), aplastic crises (2), avascular necrosis (2), leg ulcers (2), cerebrovascular accident (1), osteomyelitis (1), and retinopathy (1). Death had occurred in 4 patients, including 2 from pneumococcal sepsis/meningitis at ages 5 and 10 years, 1 of acute chest syndrome at age 14 years, and 1 of multiorgan failure at age 35 years. Zimmerman et al. (1999) concluded that Hb S/O (Arab) disease is a severe sickling hemoglobinopathy with laboratory and clinical manifestations similar to those of homozygous sickle cell anemia.


.0246 HEMOGLOBIN S (PROVIDENCE)

HBB, GLU6VAL AND LYS82ASX
  
RCV000016286...

Gale et al. (1988) described a hemoglobin carrying 2 substitutions, the standard substitution of Hb S (beta6 glu-to-val) and the substitution of Hb Providence (beta82 lys-to-asx). (There is partial postsynthetic deamination of asparagine to aspartic acid.) The double mutation is electrophoretically silent; if hemoglobin electrophoresis alone were done, the abnormality would be missed.


.0247 HEMOGLOBIN S (TRAVIS)

HBB, GLU6VAL AND ALA142VAL
  
RCV000016286...

.0248 HEMOGLOBIN SABINE

HBB, LEU91PRO
  
RCV000016581...

The hemoglobin is unstable, causing hemolytic anemia in the heterozygote. See Schneider et al. (1969) and Bogoevski et al. (1983). Hull et al. (1998) reported 2 cases of Hb Sabine, in a mother in whom the mutation had apparently arisen de novo and her son. They stated that more than 100 unstable hemoglobins causing hemolytic anemia had been described. Less than 20% of the unstable hemoglobins that have been characterized affect the alpha-globin chain.


.0249 HEMOGLOBIN SAINT JACQUES

ERYTHROCYTOSIS 6, INCLUDED
HBB, ALA140THR
  
RCV000016582...

Produces erythrocytosis by alteration of the site of fixation of 2,3-diphosphoglycerate (Rochette et al., 1984).


.0250 HEMOGLOBIN SAITAMA

HBB, HIS117PRO
  
RCV000016583

.0251 HEMOGLOBIN SAKI

HBB, LEU14PRO
  
RCV000016584...

.0252 HEMOGLOBIN SAN DIEGO

ERYTHROCYTOSIS 6, INCLUDED
HBB, VAL109MET
  
RCV000016585...

This hemoglobin is characterized by high oxygen affinity, and erythrocytosis is associated. See Anderson (1974), Nute et al. (1974), and Harkness et al. (1981). Williamson et al. (1995) observed a 30-year-old man of West Indian origin who showed compound heterozygosity for Hb San Diego and Hb S (141900.0243). He had suffered for about 6 months from severe colicky abdominal pain in episodes of several hours duration. He showed erythrocytosis with a hemoglobin value of 18.8 g/dl. The Hb San Diego mutation represented a GTG-to-ATG change. The Hb S mutation was inherited from the mother; Williamson et al. (1995) suggested that the Hb San Diego mutation occurred de novo on the chromosome 11 derived from the father. DNA testing was consistent with the assumed paternity. The Hb San Diego mutation occurred at a CpG dinucleotide. It was concluded that the abdominal pain was due to increased blood viscosity and the symptoms were relieved by venesection.


.0253 HEMOGLOBIN SANTA ANA

HBB, LEU88PRO
  
RCV000016586...

.0254 HEMOGLOBIN SAVANNAH

HBB, GLY24VAL
  
RCV000016587

.0255 HEMOGLOBIN SAVERNE

HBB, 1-BP DEL, HIS143PRO, FS
  
RCV000016588

Probable frameshift mutation resulting from deletion of the second base of the triplet coding for beta his 143; CAC becomes CCA (PRO). The last part of the beta gene code, 143rd residue on, becomes CAC-AGT-ATC-ACT-AAG-CTC-GCT-TTC-TTG-CTG-TCC-AAT-TTC-TAT-TAA, which reads pro-ser-ile-thr-lys-leu-ala-phe-leu-leu-ser-asn-phe-tyr-stop (COOH). Thus, the beta chain is 156 amino acids long rather than 146. See Delanoe et al. (1984).


.0256 HEMOGLOBIN SEATTLE

HBB, ALA70ASP
  
RCV000016589

Hemoglobin Seattle was discovered by Stamatoyannopoulos et al. (1969), who showed that it is associated with a considerable decrease in oxygen affinity with almost normal heme-heme interaction and normal Bohr effect. It was their conclusion and that of Huehns et al. (1970) that the change was ala76-to-glu. However, studies reported by Kurachi et al. (1973) led to the conclusion that Hb Seattle has a substitution of alanine by aspartic acid at position 70 of the beta polypeptide. Chow et al. (1994) reported a second example of Hb Seattle in a Ukrainian family.


.0257 HEMOGLOBIN SENDAGI

HEMOGLOBIN WARSAW
HBB, PHE42VAL
  
RCV000016590

Ogata et al. (1986) and Honig et al. (1990) studied this unstable variant, which has low oxygen affinity and an increased susceptibility to methemoglobin formation.


.0258 HEMOGLOBIN SHANGHAI

HBB, GLN131PRO
  
RCV000016592

The proband had chronic hemolytic anemia aggravated by oxidated drugs and common colds. Her 10-year-old son was also affected. Biosynthesis studies indicated a normal rate of synthesis, but relatively fast degradation of the mutant beta chain (Zeng et al., 1987).


.0259 HEMOGLOBIN SHELBY

HEMOGLOBIN LESLIE
HEMOGLOBIN DEACONESS
HBB, GLN131LYS
  
RCV000016593...

See Felice et al. (1978), Carcassi et al. (1980), and Moo-Penn et al. (1984). Deletion of glutamine at beta 131 in Hb Leslie was reported by Lutcher et al. (1976) and the same deletion was reported in Hb Deaconess by Moo-Penn et al. (1975). Later, Moo-Penn et al. (1984) showed that Hb Deaconess and Hb Leslie are identical to Hb Shelby. All three have substitution of lysine for glutamine at beta 131. Adachi et al. (1993) described a compound heterozygote for Hb S and Hb Shelby. Hb Shelby, like Hb A, can form hybrids with Hb S which participate in polymer formation in vitro. However, Hb S/Hb Shelby hybrids copolymerize with Hb S less than Hb A/S hybrids. The mild clinical presentation of the patient was attributed to this fact.


.0260 HEMOGLOBIN SHEPHERDS BUSH

HBB, GLY74ASP
  
RCV000016596

.0261 HEMOGLOBIN SHERWOOD FOREST

HBB, ARG104THR
  
RCV000016597...

See Ryrie et al. (1977).

Williamson et al. (1994) described a 22-year-old Pakistani male with polycythemia associated with homozygosity for this high-affinity hemoglobin mutant. Whereas 2 previously reported persons with the mutant hemoglobin were heterozygotes and were hematologically normal, the homozygous state was associated with compensatory erythrocytosis resulting from decreased delivery of oxygen to the tissues. Both parents and both sibs were heterozygous for the hemoglobin mutant and were hematologically normal. This may have been the first example of a beta-globin mutation producing polycythemia in homozygotes, but not in heterozygotes.


.0262 HEMOGLOBIN SHOWA-YAKUSHIJI

BETA-PLUS-THALASSEMIA
BETA-SHOWA-YAKUSHIJI THALASSEMIA
HBB, LEU110PRO
  
RCV000016598...

In a Japanese family, Kobayashi et al. (1987) and Naritomi et al. (1988) described a novel HBB mutation that produced the beta-thalassemia phenotype (613985) through a posttranslational mechanism. Substitution of proline for leucine at position 110 greatly reduced the molecular stability of the beta-globin subunit, leading to total destruction of the variant globin chains by proteolysis. The mutation could be identified after digestion with the restriction enzyme MspI. They named the variant Hb Showa-Yakushiji, after the 2 districts where the probands resided. Other variant hemoglobins that are very unstable and lead to thalassemia include Hb Indianapolis (141900.0117) and Hb Quong Sze (141900.0005).

In 4 unrelated individuals in India, Edison et al. (2005) found the hyper-unstable variant Hb Showa-Yakushiji in compound heterozygosity with other mutations producing beta-thalassemia or with Hb E (141900.0071). In all 4 patients, the mutation was found on the same haplotype, which differed from the Japanese haplotype, indicating its independent origin in India.


.0263 HEMOGLOBIN SIRIRAJ

HEMOGLOBIN G (HONAN)
HBB, GLU7LYS
  
RCV000016602...

This HBB gene variant was discovered in a Thai family by Tuchinda et al. (1965) and was subsequently identified in several Chinese by Blackwell et al. (1972). Chang et al. (1999) observed the same variant in a Taiwanese family. DNA analysis detected a G-to-A transition at the first base of codon 7 (GAG to AAG). This mutation creates an MboII site that is highly specific for Hb Siriraj.


.0264 HEMOGLOBIN SOGN

HBB, LEU14ARG
  
RCV000016604...

Hb Sogn was first described in Norway by Monn et al. (1968). Fairbanks et al. (1990) described the first known instances of Hb Sogn outside of Norway, in 2 families, both of Norwegian descent. Hb Sogn has been described in Norwegian families and in American families from the upper midwest where settlement of Scandinavian families was common. Miller et al. (1996) described the hemoglobin variant in a family residing in Illinois; the proband's maternal grandfather was Norwegian. Codon 14 showed a CTG (leu)-to-CGG (arg) change. The proband married a person who was homozygous for alpha-thalassemia-2. The couple had 2 daughters who offered the opportunity of comparing data between Hb Sogn heterozygotes with 4 alpha-globin genes and 3 alpha-globin genes. Mild microcytosis and hypochromia in the father was due to the presence of alpha-thal-2 homozygosity and that in the mother to the presence of the mildly unstable Hb Sogn. Striking microcytosis and hypochromia in 1 daughter could be attributed to the combination of a the alpha-thal-2 trait and Hb Sogn heterozygosity.


.0265 HEMOGLOBIN SOUTHAMPTON

HEMOGLOBIN CASPER
HBB, LEU106PRO
  
RCV000016605...

See Hyde et al. (1972), Jones et al. (1973), and Koler et al. (1973), who described Hb Southampton (Casper) as a leu106-to-pro substitution in the HBB gene.

Nusapan and Conant (2023) noted that Hb Southampton (Casper) is a rare unstable hemoglobinopathy caused by a c.320T-C transition in the HBB gene, resulting in a leu107-to-pro (L107P) substitution. The mutation results in distortion of the tertiary structure of the hemoglobin molecule, leading to membrane damage and RBC destruction. Hepatosplenomegaly, chronic hemolytic anemia, and methemoglobinemia are common features. Macrocytosis is sometimes observed.


.0266 HEMOGLOBIN SOUTH FLORIDA

HBB, NH2 EXTENSION, VAL1MET, METi RETAINED
  
RCV000016609...

The initiator methionine residue (METi) is preserved. This variant was first discovered in a patient who appeared to have markedly elevated Hb A(1c) as estimated by ion exchange chromatography. Glycosylated hemoglobin measured by a colorimetric method with thiobarbituric acid was normal, however. If it were not for the fact that methionine is 1 of the 4 N-terminal amino acids (alanine, glycine, serine, methionine) that participate in acetylation, this abnormal amino acid substitution would have gone unrecognized. Acetylation of the N-terminal methionine residue occurs less easily than in other amino acids; thus, hemoglobin South Florida could not be recognized by hemoglobin electrophoresis. In contrast, acetylation of alanine in hemoglobin Raleigh is 100% and that variant can be recognized by hemoglobin electrophoresis. See Boissel et al. (1985) and Shah et al. (1986). Malone et al. (1987) reported a family study. The fundamental change is not in the codon for the initiator mutation but in the codon for the first residue for the mature beta-globin chain, valine, which is converted to methionine. Because the initiator methionine is retained, this methionine is substituted for valine as residue 2 in the mature chain of Hb South Florida.


.0267 HEMOGLOBIN ST. ANTOINE

HBB, GLY74DEL AND LEU75DEL
  
RCV000016610

Two amino acids, glycine and leucine, are deleted from beta 74 and 75. See Wajcman et al. (1973).


.0268 HEMOGLOBIN ST. LOUIS

HEINZ BODY HEMOLYTIC ANEMIA
HBB, LEU28GLN
  
RCV000016611...

This is a form of Hb M, differing from other Hb M variants by the fact that the substitution is not for the histidine at E7 or F8. Hb M (Milwaukee) is another. Severe Heinz body anemia, in addition to methemoglobinemia, is associated with Hb St. Louis. The beta heme group is permanently in a ferric state. See Cohen-Solal et al. (1974), Anderson (1976), Thillet et al. (1976), and Wiedermann et al. (1986).


.0269 HEMOGLOBIN ST. MANDE

HBB, ASN102TYR
  
RCV000016603

This hemoglobin variant has a low oxygen affinity, resulting in cyanosis. See Arous et al. (1981). Poyart et al. (1990) found that the functional properties of St. Mande are intermediary between those of normal Hb A and Hb Kansas (0.0145).


.0270 HEMOGLOBIN STANMORE

HBB, VAL111ALA
  
RCV000016607

.0271 HEMOGLOBIN STRASBOURG

HBB, VAL23ASP
  
RCV000016608...

Hb Strasbourg was first observed in a female from northern Portugal and in 1 of her 2 children. Garel et al. (1976) incorrectly thought that the valine at position 20 was substituted. See Forget (1977). Bisse et al. (1998) provided information on a German family with the same abnormality. This was the second observation of this hemoglobin variant. The 23-year-old propositus had a hemoglobin level of 19.8 g/dl. The variant was shown to have a high oxygen affinity. Codon 23 of the HBB gene was changed from GTT (val) to GAT (asp).


.0272 HEMOGLOBIN SUMMER HILL

HBB, ASP52HIS
  
RCV000016613...

No hematologic abnormality. See Wilkinson et al. (1980) and Cin et al. (1983).


.0273 HEMOGLOBIN SUNNYBROOK

HBB, PRO36ARG
  
RCV000016614

.0274 HEMOGLOBIN SYDNEY

HBB, VAL67ALA
  
RCV000016615

Like hemoglobins Koln and Genova, this hemoglobin has no electrophoretic abnormality but is unstable, forming intracellular precipitates. See Carrell et al. (1967) and Casey et al. (1978).


.0275 HEMOGLOBIN SYRACUSE

ERYTHROCYTOSIS 6, INCLUDED
HBB, HIS143PRO
  
RCV000016616...

.0276 HEMOGLOBIN T (CAMBODIA)

HBB, GLU26LYS AND GLU121GLN
  
RCV000016317...

See Barwick et al. (1985). Combines substitutions of Hb E and Hb O (Arab): substitution of lysine for glutamic acid at beta 26 and of glutamine for glutamic acid at beta 121.


.0277 HEMOGLOBIN TA-LI

HBB, GLY83CYS
  
RCV000016618...

.0278 HEMOGLOBIN TACOMA

HEINZ BODY HEMOLYTIC ANEMIA
HBB, ARG30SER
  
RCV000016619...

.0279 HEMOGLOBIN TAK

HBB, +8 RESIDUES
  
RCV000016621...

The usual terminal dipeptide 145-146 of the beta chain is lacking and is replaced by 10 residues attached to the C-terminal end. Hemoglobin Constant Spring is a termination defect of the alpha chain. See Flatz et al. (1971). Characterized on the basis of amino acid analysis, this variant was assumed to be due to an insertion of the dinucleotide CA into codon 146, CAC-to-CA(CA)C, which abolished the normal stop codon at position 147 and caused a frameshift with elongation of the beta chain by 11 amino acids. The variant had previously been described in a few Thai families. Hoyer et al. (1998) reported the DNA sequence of Hb Tak in an individual of Cambodian descent who was a Hb E/Tak compound heterozygote. In contrast with extended variants of the alpha-globin gene that are expressed as alpha-thalassemias, the hematologic effect of Hb Tak/Hb E was a mild polycythemia. The combination of Hb Tak/Hb E was not expressed as a thalassemia.

Shih et al. (2005) reported heterozygosity for Hb Tak in a Taiwanese individual.


.0280 HEMOGLOBIN TAKAMATSU

HBB, LYS120GLN
  
RCV000016622

.0281 HEMOGLOBIN TAMPA

HBB, ASP79TYR
  
RCV000016623...

.0282 HEMOGLOBIN TIANSHUI

HBB, GLN39ARG
  
RCV000016624

In a healthy 34-year-old Chinese male of Han nationality, Li et al. (1990) identified a hemoglobin variant and showed that it had a replacement of glutamine by arginine at residue 39.


.0283 HEMOGLOBIN TILBURG

HBB, ASP73GLY
  
RCV000016625

This hemoglobin and 3 others with a single amino acid substitution at the same site have reduction in affinity for oxygen. See Bernini and Giordano (1988).


.0284 HEMOGLOBIN TOCHIGI

HBB, GLY56DEL, ASN57DEL, PRO58DEL, LYS59DEL
  
RCV000016626

Deletion of residues 56-59 of the beta chain. See Shibata et al. (1970).


.0285 HEMOGLOBIN TOURS

HBB, THR87DEL
  
RCV000016627

.0286 HEMOGLOBIN TOYOAKE

HBB, ALA142PRO
  
RCV000016628

.0287 HEMOGLOBIN TUBINGEN

HBB, LEU106GLN
  
RCV000016630

See Kohne et al. (1976). Philippe et al. (1993) described this hemoglobin variant, a cause of methemoglobinemia, in a 53-year-old Belgian woman. Her father had been cyanotic throughout his life. This was the second report of this hemoglobin variant.


.0288 HEMOGLOBIN TUNIS

HBB, PRO124SER
  
RCV000016631

.0289 HEMOGLOBIN TY GARD

ERYTHROCYTOSIS 6, INCLUDED
HBB, PRO124GLN
  
RCV000016632...

.0290 HEMOGLOBIN VAASA

HBB, GLN39GLU
  
RCV000016633

.0291 HEMOGLOBIN VANCOUVER

HBB, ASP73TYR
  
RCV000016634

.0292 HEMOGLOBIN VANDERBILT

ERYTHROCYTOSIS 6, INCLUDED
HBB, SER89ARG
  
RCV000016635...

.0293 HEMOGLOBIN VICKSBURG

HBB, LEU75DEL
  
RCV000016636

See Adams et al. (1981). When they failed to find evidence of deletion of leu75 in genomic DNA, Coleman et al. (1988) proposed somatic mutation. A more plausible explanation, perhaps, is one parallel to that obtaining in the case of Hb Atlanta-Coventry (141900.0013).


.0294 HEMOGLOBIN VILLEJUIF

HBB, THR123ILE
  
RCV000016637...

This mutation was discovered as a silent and asymptomatic variant in an 87-year-old French woman who coincidentally had polycythemia vera (Wajcman et al., 1989).. Carbone et al. (2001) reported the second observation of this hemoglobin variant in 3 related subjects from Montesarchio in southern Italy. The DNA change was ACC to ATC.


.0295 HEMOGLOBIN VOLGA

HEMOGLOBIN DRENTHE
HBB, ALA27ASP
  
RCV000016638...

.0296 HEMOGLOBIN WARWICKSHIRE

HBB, PRO5ARG
  
RCV000016640

.0297 HEMOGLOBIN WIEN

HBB, TYR130ASP
  
RCV000016641

.0298 HEMOGLOBIN WILLAMETTE

HBB, PRO51ARG
  
RCV000016629

.0299 HEMOGLOBIN WINDSOR

HBB, VAL11ASP
  
RCV000016642

Gilbert et al. (1989) found this variant in a 9-month-old child who presented with hemolytic anemia in association with intercurrent viral infection. Instability of the hemoglobin molecule as well as increase in oxygen affinity was demonstrated.


.0300 HEMOGLOBIN WOOD

ERYTHROCYTOSIS 6, INCLUDED
HBB, HIS97LEU
  
RCV000016643...

.0301 HEMOGLOBIN YAKIMA

ERYTHROCYTOSIS 6, INCLUDED
HBB, ASP99HIS
  
RCV000016644...

Polycythemia occurs with this hemoglobinopathy as with hemoglobin Chesapeake. See Jones et al. (1967), Novy et al. (1967), and Osgood et al. (1967).


.0302 HEMOGLOBIN YAMAGATA

HBB, LYS132ASN
  
RCV000016645

See Harano et al. (1990).

Hemoglobin Yamagata as reported by Harano et al. (1990) was caused by a change of codon 132 in the HBB gene from AAA (lys) to AAC (asn). Han et al. (1996) found the same amino acid substitution in a 37-year-old Korean woman to be caused by a change of codon 132 from AAA to AAT. No distinctive clinical abnormalities were detected.


.0303 HEMOGLOBIN YATSUSHIRO

HBB, VAL60LEU
  
RCV000016646

.0304 HEMOGLOBIN YOKOHAMA

HBB, LEU31PRO
  
RCV000016647

See Nakatsuji et al. (1981). Plaseska et al. (1991) described a de novo mutation in a Yugoslavian boy with severe transfusion-dependent hemolytic anemia. The patients of Nakatsuji et al. (1981) were a 33-year-old Japanese woman with chronic hemolytic anemia and her son with milder symptoms.


.0305 HEMOGLOBIN YORK

ERYTHROCYTOSIS 6, INCLUDED
HBB, HIS146PRO
  
RCV000016648...

.0306 HEMOGLOBIN YOSHIZUKA

HBB, ASN108ASP
  
RCV000016649

Reduced oxygen affinity like hemoglobin Kansas. See Imamura et al. (1969).


.0307 HEMOGLOBIN YPSILANTI

ERYTHROCYTOSIS 6, INCLUDED
HBB, ASP99TYR
  
RCV000016650...

Substitution in beta chain results in increased oxygen affinity leading to erythremia and abnormal polymerization manifested in heterozygotes by hybrid hemoglobin molecules containing both the Ypsi beta chain and the normal beta chain. See Glynn et al. (1968).


.0308 HEMOGLOBIN YUKUHASHI

HEMOGLOBIN DHOFAR
HBB, PRO58ARG
  
RCV000016651...

.0309 HEMOGLOBIN YUSA

HBB, ASP21TYR
  
RCV000016653...

.0310 HEMOGLOBIN ZURICH

HBB, HIS63ARG
  
RCV000016654...

Drug-induced hemolysis results from this variant hemoglobin. The affinity of Hb Zurich for carbon monoxide is about 65 times that observed in normal hemoglobin A. Carboxyhemoglobin content in persons with Hb Zurich varied from 3.9 to 6.7% for nonsmokers and 9.8 to 19.7% for smokers. Hemolysis was less in smokers, presumably because of stabilization of Hb Zurich by CO. See Huisman et al. (1960), Muller and Kingma (1961), Frick et al. (1962), Rieder et al. (1965), Dickerman et al. (1973), Zinkham et al. (1979, 1980, 1983), Dlott et al. (1983), and Virshup et al. (1983).

Miranda et al. (1994) identified Hb Zurich in a 38-year-old woman who had a hemolytic crisis after administration of an antibiotic for urinary tract infection. This hemoglobin variant was first identified by protein analysis and then by DNA sequencing.

Aguinaga et al. (1998) studied 4 members of a Kentucky family whom they had identified as Hb Zurich carriers. During pregnancy, the proband developed hemolytic anemia with Heinz bodies when treated for a urinary tract infection with sulfonamide. Because of severe anemia, the patient was transfused several times and ultimately splenectomized. The Kentucky family studied in this report was part of a larger kindred that was known to contain 19 members who were Hb Zurich carriers.

Zinkham et al. (1979) demonstrated in vitro thermal denaturation of Hb Zurich as a cause of anemia during fever.


.0311 BETA-ZERO-THALASSEMIA

HBB, LYS17TER
  
RCV000016655...

This variant was found in Chinese with beta-zero-thalassemia (613985). Chang et al. (1979) and Chang and Kan (1979) presented evidence that beta-zero-thalassemia is a nonsense mutation, the first identified in man. By molecular hybridization they showed that the beta gene is present. In different patients variable amounts of beta-like globin mRNA is present. They sequenced mRNA and found that noncoding regions at both ends were normal but at the position corresponding to amino acid no. 17, the normal lysine codon AAG was converted to UAG, a terminator. Such a nonsense mutation should be overcome by means of suppressor tRNA which allows the ribosome to read through a terminator codon by inserting an amino acid. In vitro addition of a serine suppressor tRNA from yeast resulted in human beta-globin synthesis. Cell-free assays with suppressor tRNAs may be useful for detecting nonsense mutations in other human genetic disorders. Steger et al. (1993) showed that this AAG-to-TAG nonsense mutation and the hemoglobin E mutation, common causes of beta(+)-thalassemia and beta-zero-thalassemia in Southeast Asia, can be detected using allele-specific PCR, known also as the amplification refractory mutation system (ARMS).

Krawczak et al. (2000) pointed out that this was the first single basepair substitution in a human gene underlying a genetic disorder to be reported. Knowledge of the amino acid substitution responsible for sickle hemoglobin permitted imperfect inference of the nucleotide change because of redundancy of the code.


.0312 BETA-ZERO-THALASSEMIA

HBB, GLN39TER
  
RCV000016656...

Chehab et al. (1986) found evidence for new mutation in the codon at beta-39 from CAG (glutamine) to the stop codon TAG. The beta-39 nonsense mutation is the second most common beta-thalassemia (613985) lesion in Italy, accounting for a third of cases, and the most common in Sardinia, accounting for 90% of cases there. In Sardinia, the beta-39 mutation has been identified with 9 different haplotypes. All this suggested to Chehab et al. (1986) that beta-39 is a mutation hotspot. Trecartin et al. (1981) found that the form of beta-zero-thalassemia that is predominant in Sardinia is caused by a single nucleotide mutation at the position corresponding to amino acid number 39 and converting a glutamine codon (CAG) to an amber termination codon (UAG). (Epstein et al. (1963) described 'amber' mutants of phage T4 in a frequently cited paper in a Cold Spring Harbor Symposium on Quantitative Biology. The origin of the unusual name 'amber' is, as Witkowski (1990) called it, 'an interesting footnote in the history of molecular biology.' Edgar (1966) recounted that R. H. Epstein and C. M. Steinberg, then at the California Institute of Technology, had promised Harris Bernstein, then at Yale University, that the mutants, if any were found, would be named after his mother. They were found and were named 'amber,' the English equivalent of 'Bernstein.' The other 2 'stop' codons, UGA and UAA, are sometimes referred to as 'opal' and 'ochre,' respectively.) Rosatelli et al. (1992) used denaturing gradient gel electrophoresis (DGGE) followed by direct sequence analysis of amplified DNA to study 3,000 beta-thalassemia chromosomes in the Sardinian population. They confirmed that the predominant mutation, present in 95.7% of beta-thalassemia chromosomes, was gln39-to-ter.


.0313 BETA-ZERO-THALASSEMIA

HBB, TRP15TER
  
RCV000016657...

The trp15-to-ter (W15X) mutation that Kazazian et al. (1984) demonstrated in Asian beta-thalassemia (613985) patients was the result of a TGG-to-TAG mutation. Ribeiro et al. (1992) demonstrated the frequent occurrence in central Portugal of beta-zero-thalassemia due to a change of codon 15 for tryptophan to a stop codon; the basis, however, was a TGG-to-TGA mutation.


.0314 BETA-THALASSEMIA, DOMINANT INCLUSION BODY TYPE

HBB, GLU121TER
  
RCV000016658...

See Kazazian et al. (1986), Fei et al. (1989) and Adams et al. (1990).

Thein et al. (1990) identified the E121X mutation in 3 British families with dominantly inherited inclusion body beta-thalassemia (603902). The clinical features were that of a dominant dyserythropoietic anemia associated with inclusion bodies in normoblasts. The condition was described originally by Weatherall et al. (1973) and was previously labeled dyserythropoietic, congenital, Irish or Weatherall type. The original family reported by Weatherall et al. (1973) was found by Thein et al. (1990) to carry an insertion/deletion mutation with frameshift in the HBB gene (141900.0520).


.0315 BETA-ZERO-THALASSEMIA

HBB, TRP37TER
  
RCV000016659...

.0316 BETA-ZERO-THALASSEMIA

HBB, GLU43TER
  
RCV000016660...

Atweh et al. (1988) described a novel nonsense mutation in a Chinese patient with beta-zero-thalassemia (613985): a G-to-T substitution at the first position of codon 43, which changed the glutamic acid coding triplet (GAG) to a terminator codon (TAG). They incorrectly referred to a patient carrying both the beta-17 and the beta-43 nonsense mutation as being a double heterozygote rather than a compound heterozygote.


.0317 BETA-ZERO-THALASSEMIA

HBB, LYS61TER
  
RCV000016661...

.0318 BETA-ZERO-THALASSEMIA

HBB, TYR35TER
  
RCV000016662...

.0319 HEMOGLOBIN HOUSTON

BETA-PLUS-THALASSEMIA, DOMINANT
BETA-HOUSTON-THALASSEMIA
HBB, GLN127PRO
  
RCV000016664...

In a person of British extraction, Kazazian et al. (1989) found a gln127-to-pro mutation as the basis of a 'dominant' form of beta-plus-thalassemia (613985). This form of thalassemia is due to instability of the beta-globin chains containing the particular mutation. Kazazian et al. (1992) again reported on the CAG-CGG missense mutation at codon 127 which caused thalassemia intermedia with hemolysis in 3 generations of a British-American family. They commented that the paucity of high-frequency exon 3 mutations and the worldwide distribution of the few that are observed are probably attributable to their phenotypic severity and lack of increased genetic fitness in relation to malaria.


.0320 BETA-PLUS-THALASSEMIA

HBB, GLN127PRO AND ALA128DEL
  
RCV000016665

In a Japanese patient with beta-plus-thalassemia (613985), Hattori et al. (1989) found deletion of nucleotides AGG from codons 127 and 128 (CAG to GCT) resulting in replacement of gln127 and ala128 by proline (CCT).


.0321 BETA-PLUS-THALASSEMIA

HEMOGLOBIN CAGLIARI
HBB, VAL60GLU
  
RCV000016666...

In an Italian with beta-plus-thalassemia (613985), Podda et al. (1989, 1991) found a val60-to-glu substitution.


.0322 BETA-ZERO-THALASSEMIA

HBB, LYS8FS
  
RCV000016669...

A frameshift mutation, -AA in codon 8, AAG to G, in the HBB gene was found in a Turkish patient with beta-zero-thalassemia (613985) by Orkin and Goff (1981). This mutation was also found in homozygous state in DNA from the archaeologic remains of a child with severe bone pathology consistent with thalassemia (Filon et al., 1995). The remains came from a grave thought to date to the Ottoman period, sometime between the 16th and 19th centuries. From the tooth development, it was estimated that the child died at the age of about 8 years, whereas patients with this mutation would be expected to be transfusion-dependent from early infancy. Filon et al. (1995) also found a rare DNA polymorphism: a C-to-T transition in the second codon of the HBB gene that did not alter the corresponding amino acid. This polymorphism is found in 13% of present-day Mediterranean beta-thalassemia chromosomes and is part of a haplotype (haplotype IV) that is associated with relatively high levels of fetal hemoglobin. The disease may have run a milder course because of linkage to haplotype IV.


.0323 BETA-ZERO-THALASSEMIA

HBB, GLY16FS
  
RCV000016670...

A frameshift mutation, -C, codon 16, GGC to GG, in the HBB gene was found in Asian Indians with beta-zero-thalassemia (613985) by Kazazian et al. (1984).


.0324 BETA-ZERO-THALASSEMIA

HBB, SER44FS
  
RCV000016671...

Frameshift, -C, codon 44, TCC to TC, was found in a Kurdish patient with beta-zero-thalassemia (613985) by Kinniburgh et al. (1982).


.0325 BETA-ZERO-THALASSEMIA

HBB, 1-BP INS, G, CODONS 8/9
  
RCV000016672...

Frameshift, +G, codons 8/9, AAGTCT to AAGGTCT was found in an Asian Indian with beta-zero-thalassemia (613985) by Kazazian et al. (1984).


.0326 BETA-ZERO-THALASSEMIA

HBB, 4-BP DEL, 41/42CTTT
  
RCV000016673...

Frameshift, -4, codons 41/42, TTCTTT to TT, was found in an Asian Indian with beta-zero-thalassemia (613985) by Kazazian et al. (1984) and in Chinese by Kimura et al. (1983).

Lau et al. (1997) found that the deletion of CTTT at codons 41/42 accounted for 40% of all beta-thalassemia alleles in Hong Kong. Chiu et al. (2002) designed allele-specific primers and a fluorescent probe for detection of this mutation in the HBB gene from maternal plasma by real-time PCR. Using this method, they showed that beta-thalassemia major could be excluded from fetal inheritance by demonstrating absence of inheritance of the paternally transmitted mutation. By studying circulating fetal DNA in the maternal plasma for this mutation, Chiu et al. (2002) added beta-thalassemia to the list of disorders that could be prenatally diagnosed using this noninvasive method, which had previously demonstrated usefulness in diagnosing sex-linked diseases (Costa et al., 2002) and fetal rhesus D status (Lo et al., 1998).


.0327 BETA-ZERO-THALASSEMIA

HBB, GLU6FS
  
RCV000016674...

Frameshift, -A, codon 6, GAG to GG, was found in Mediterranean patients by Kazazian et al. (1983). Bouhass et al. (1990) found the same mutation in an Algerian patient who was a genetic compound. Rosatelli et al. (1992) found that this mutation accounted for 2.1% of mutations carried by 3,000 beta-thalassemia chromosomes from the Sardinian population. Romey et al. (1993) described an improved procedure that allows the detection of single basepair deletions on nondenaturing polyacrylamide gels and demonstrated its applicability for identifying this mutation.


.0328 BETA-ZERO-THALASSEMIA

HBB, PHE71FS
  
RCV000016675...

Frameshift, +A, codons 71/72, TTAGT to TTTAAGT, was found in Chinese by Cheng et al. (1984).


.0329 BETA-ZERO-THALASSEMIA

HBB, LEU106FS
  
RCV000016668...

Frameshift, +G, codons 106/107, CTGGGC to CTGGGGG, was found in American blacks by Wong et al. (1987).


.0330 BETA-ZERO-THALASSEMIA

HBB, ALA76FS
  
RCV000016676...

Frameshift, -C, codon 76, GCT to GT, was found in an Italian by Di Marzo et al. (1988). Rosatelli et al. (1992) found that this mutation was responsible for 0.7% of the mutations carried by 3,000 beta-thalassemia chromosomes in the Sardinian population.


.0331 BETA-ZERO-THALASSEMIA

HBB, TRP37FS
  
RCV000016688...

Frameshift, -G, codon 37, TGG to G, was found in a Kurdish patient by Rund et al. (1989, 1991).


.0332 BETA-ZERO-THALASSEMIA

HBB, PRO5FS
  
RCV000016678...

Frameshift, -CT, codon 5, CCT to CC, was found in a Mediterranean patient by Kollia et al. (1989).


.0333 BETA-ZERO-THALASSEMIA

HBB, VAL11FS
  
RCV000016679...

Frameshift, -T, codon 11, GTT to GT, was found in a Mexican patient by Economou et al. (1990).


.0334 BETA-ZERO-THALASSEMIA

HBB, TYR35FS
  
RCV000016680...

Frameshift, -C, codon 35, TAC to TA, was found in Indonesia by Yang et al. (1989).


.0335 BETA-ZERO-THALASSEMIA

HEMOGLOBIN GENEVA
HBB, ASP114FS
  
RCV000016681

Frameshift, -CT, codon 114, CTG to G, was found in a French patient by Beris et al. (1988). Hb Geneva is an unstable hemoglobin producing a hemolytic anemia with inclusion bodies in the peripheral blood after splenectomy. Heterozygotes show manifestations of a thalassemia-like disorder.


.0336 BETA-ZERO-THALASSEMIA

HBB, LEU14FS
  
RCV000016683...

Frameshift, +G, codon 14/15, CTGTGG to CTGGTGG, was found in Chinese by Chan et al. (1988).


.0337 BETA-ZERO-THALASSEMIA

HBB, TRP37FS
  
RCV000016684...

Frameshift, -7 nucleotides from codons 37-39, TGGACCCAG, was found in a Turkish patient by Schnee et al. (1989).


.0338 BETA-ZERO-THALASSEMIA

HBB, ASP94FS
  
RCV000016685...

Frameshift, +TG, codon 94 (GAC), was found in a Mediterranean patient by Pirastu et al. (1990).


.0339 BETA-ZERO-THALASSEMIA

HBB, GLY64FS
  
RCV000016686...

Frameshift, -G, codon 64, GGC to GC, was found in a Swiss woman heterozygous for beta-thalassemia by Chehab et al. (1989). This was a spontaneous mutation as originally described by Tonz et al. (1973). The father was 45 years old when the proband was born. By haplotyping, Chehab et al. (1989) showed, furthermore, that the mutation had arisen on the father's chromosome 11.


.0340 BETA-ZERO-THALASSEMIA

HBB, VAL109FS
  
RCV000016687...

Frameshift, -G, codon 109, GTG to TG, found in a Lithuanian by Kazazian et al. (1989).


.0341 BETA-ZERO-THALASSEMIA

HBB, PRO36FS
  
RCV000016688...

Frameshift, -T, codon 36/37, CCTTGG to CCTGG, was found in Iranian Kurds by Rund et al. (1989, 1991).


.0342 BETA-ZERO-THALASSEMIA

HBB, ALA27FS
  
RCV000016689...

Frameshift, +C, codons 27/28, GCCCTG to GCCCCTG, was found in Chinese by Cai et al. (1989).


.0343 BETA-ZERO-THALASSEMIA

HBB, PHE71FS
  
RCV000016690...

Frameshift, +T, codon 71, TTT to TTTT, was found in Chinese by Kazazian (1990).


.0344 BETA-ZERO-THALASSEMIA

HBB, MET1ARG
  
RCV000016691...

This initiator codon mutant, ATG to AGG, was found in Chinese individuals by Kazazian (1990).


.0345 BETA-ZERO-THALASSEMIA

BETA-THALASSEMIA, LERMONTOV TYPE
HBB, MET1THR
  
RCV000016692...

This initiator codon mutant, ATG to ACG, was found in Yugoslavians with beta-zero-thalassemia (613985) by Jankovic et al. (1989). The same mutation was found by Beris et al. (1993) in a father and daughter of a family originating from Bern, Switzerland. Unlike the first reported family, of Yugoslavian origin, the Swiss patients had high Hb F levels. The mutation converted the initiator methionine to threonine and abolished an NcoI recognition site.

(In the case of many other genes in which the mutations have been characterized on the basis of the gene itself, the codon count begins with the initiator methionine. In such a system, this mutation would be designated met1-to-thr and the hemoglobin S mutation would be designated glu7-to-val.)

Molchanova et al. (1998) characterized the beta-thalassemia present in 3 generations of a branch of the family of the Russian poet Mihail Yurievich Lermontov. The hematologic data for affected members of 3 generations were compatible with a beta-thal heterozygosity. Sequence analysis showed an ATG-to-ACG change in the initiation codon. The family in which it was first observed by Jankovic et al. (1989, 1990) was said to have been of Croatian origin. In that family, the mutation was accompanied by a CAC-to-CAT change in codon 2 of the same chromosome; this common polymorphism was not seen in the Russian family.


.0346 BETA-ZERO-THALASSEMIA

HBB, IVS1, G-A, +1
  
RCV000016694...

Splice junction mutant, G to A, position 1 of IVS1, was found by Orkin et al. (1982) in a Mediterranean patient.


.0347 BETA-ZERO-THALASSEMIA

HBB, IVS1, G-T, +1
  
RCV000016695...

Splice junction mutant, G to T, at position 1 of IVS1 was found in an Asian Indian and in Chinese by Kazazian et al. (1984).


.0348 BETA-ZERO-THALASSEMIA

HBB, IVS2, G-A, +1
  
RCV000016696...

A splice junction mutant, G to A, at position 1 of IVS2 was found in a Mediterranean by Treisman et al. (1982), in a Tunisian by Chibani et al. (1988), and in an American black by Thein et al. (1988). The same mutation was found by Hattori et al. (1992), who referred to the mutation as IVS2-1 (G-A).

This is one of the earliest mutations at a 5-prime splice site to be described. In an analysis of 101 different examples of point mutations that lie in the vicinity of mRNA splice junctions and that have been held to be responsible for human genetic disease by altering the accuracy or efficiency of mRNA splicing, Krawczak et al. (1992) found that 62 were located at 5-prime splice sites, 26 at 3-prime splice sites, and 13 resulted in the creation of novel splice sites. They estimated that up to 15% of all point mutations causing human genetic disease result in an mRNA splicing defect. Of the 5-prime splice site mutations, 60% involve the invariant GT dinucleotides.

Sierakowska et al. (1996) found that treatment of mammalian cells stably expressing the IVS2-654 beta HBB gene with antisense oligonucleotides targeted at the aberrant splice sites restored correct splicing in a dose-dependent fashion, generating correct human beta-globin mRNA and polypeptide. Both products persisted for up to 72 hours after treatment. The oligonucleotides modified splicing by a true antisense mechanism without overt unspecific effects on cell growth and splicing of other pre-mRNAs. Sierakowska et al. (1996) stated that this novel approach in which antisense oligonucleotides are used to restore rather than to downregulate the activity of the target gene is applicable to other splicing mutants and is of potential clinical interest.

This mutation is frequent among patients in southern China and Thailand, accounting for 20% of beta-thalassemia in some regions. It causes aberrant RNA splicing. Lewis et al. (1998) modeled this mutation in mice, replacing the 2 (cis) murine adult beta-globin genes with a single copy of the human mutant HBB gene. No homozygous mice survived postnatally. Heterozygous mice carrying this mutant gene produced reduced amounts of mouse beta-globin chains and no human beta globin, and had a moderately severe form of beta-thalassemia. Heterozygotes showed the same aberrant splicing as their human counterparts and provided an animal model for testing therapies that correct splicing defects at either the RNA or DNA level.


.0349 BETA-ZERO-THALASSEMIA

HBB, IVS1, T-G, +2
  
RCV000016697...

Splice junction mutant, T to G, at position 2 of IVS1 was found in a Tunisian by Chibani et al. (1988).


.0350 BETA-ZERO-THALASSEMIA

HBB, IVS1, T-C, +2
  
RCV000030003...

Splice junction mutant, T to C, at position 2 of IVS1 was found in an American black by Gonzalez-Redondo et al. (1989). Of 33 thalassemic chromosomes in Algerian patients studied by Bouhass et al. (1990), 7 carried the T-to-C transition at position 2 in IVS1. Thus, the mutation may be common in the Algerian population. They observed 2 patients who were homozygous for the substitution and had no detectable Hb A by standard electrophoresis procedures. Interestingly, the other 2 possible changes at this position have also been observed; see 141900.0349 and 141900.0392.


.0351 BETA-ZERO-THALASSEMIA

HBB, IVS1, 17-BP DEL
  
RCV000016699...

Deletion of 17 nucleotides that removed the acceptor splice site from IVS1 was found in a Kuwaiti by Kazazian and Boehm (1988).


.0352 BETA-ZERO-THALASSEMIA

HBB, IVS1, 25-BP DEL
  
RCV000016700...

Deletion of 25 nucleotides that removed the acceptor splice site of IVS1 was found in an Asian Indian by Orkin et al. (1983).


.0353 BETA-ZERO-THALASSEMIA

HBB, IVS2, A-G, -2
  
RCV000016701...

Change from CCACAGC to CCACGGC (A to G at position -2) in the acceptor splice site of IVS2 was found in American blacks by Antonarakis et al. (1984) and Atweh et al. (1985).

This is one of the earliest-described examples of mutation in the 3-prime splice site affecting mRNA splicing. In an analysis of 101 different examples of point mutations occurring in the vicinity of mRNA splice junctions and resulting in human genetic disease, Krawczak et al. (1992) found that 26 involved 3-prime splice sites.


.0354 BETA-ZERO-THALASSEMIA

HBB, IVS2, A-C, -2
  
RCV000016702...

Change from CCACAGC to CCACCGC (A to C at position -2) at acceptor splice site of IVS2 was found in American blacks by Padanilam and Huisman (1986).


.0355 BETA-ZERO-THALASSEMIA

HBB, IVS1, 44-BP, SS DEL
  
RCV000016703...

Deletion of 44 nucleotides that removed the IVS1 donor splice site was found in a Mediterranean patient by Kazazian and Boehm (1988).


.0356 BETA-ZERO-THALASSEMIA

HBB, IVS1, G-A, -1
  
RCV000016704...

In an Egyptian child with thalassemia major, Deidda et al. (1990) found heterozygosity for a G-to-A substitution at position -1 of IVS1, which altered the conserved dinucleotide AG present in the consensus acceptor sequence. The other chromosome carried the T-to-C mutation at position 6 of the first intervening sequence (IVS1) (141900.0360). The latter mutation was associated with haplotype 6, frequently observed in Mediterranean areas; the new mutation was associated with haplotype 1. This gene can be added to the list of mutations that can be identified by Southern analysis using AflII.


.0357 BETA-PLUS-THALASSEMIA

HBB, IVS1, G-C, +5
  
RCV000016705...

A G-to-C change at position 5 of the donor site consensus sequence of IVS1 (CAG-GTTGGT to CAG-GTTGCT) was found in an Asian Indian with beta-plus-thalassemia (613985) by Kazazian et al. (1984) and in a Chinese with the same disorder by Cheng et al. (1984).


.0358 BETA-PLUS-THALASSEMIA

HBB, IVS1, G-T, +5
  
RCV000016706...

This mutation is a cause of beta-plus-thalassemia (613985). A G-to-T change at position 5 of the donor site consensus sequence of IVS1 (CAG-gttggt-to-CAG-gttgtt) was found in a Mediterranean patient and an Anglo-Saxon patient by Atweh et al. (1987) and in an American black by Gonzalez-Redondo et al. (1988). The 2 cases of Atweh et al. (1987) were in different RFLP backgrounds, suggesting that they represented independent mutations. Atweh et al. (1987) showed that after transfer of the cloned genes into HeLa cells, followed by transient expression, partial inactivation of the normal donor splice site of IVS1 and activation of 2 major and 1 minor cryptic splice sites occur. The effects of this mutation on mRNA splicing were similar to those of another beta-thalassemia gene with a G-to-C transition at the same position (141900.0357). In a rare case of beta-thalassemia in a German family, Eigel et al. (1989) found a G-to-T transversion at the intron 1 donor site of the beta-globin gene. This may be the same mutation. The patient was homozygous for this mutation and had died at age 27 of heart failure resulting from iron overload.


.0359 BETA-PLUS-THALASSEMIA

HBB, IVS1, G-A, +5
  
RCV000016707...

A G-to-A change at position 5 of the donor site consensus sequence of IVS1 (CAG-GTTGGT to CAGGTTGAT) was found in an Algerian patient with beta-plus-thalassemia (613985) by Lapoumeroulie et al. (1986).


.0360 BETA-PLUS-THALASSEMIA

HBB, IVS1, T-C, +6
  
RCV000016708...

T-to-C change at position 6 of the donor site consensus sequence of IVS1 (CAG-GTTGGT to CAG-GTTGGC) was found in a Mediterranean patient by Orkin et al. (1982).


.0361 BETA-PLUS-THALASSEMIA

HBB, IVS2, C-A, -3
  
RCV000016709...

A C-to-A change at position -3 in the acceptor splice site of IVS2 (CAG to AAG) was found in an Iranian, an Egyptian, and an American black by Gonzalez-Redondo et al. (1988) and Wong et al. (1989).


.0362 BETA-PLUS-THALASSEMIA

HBB, IVS1, T-G, -3
  
RCV000016710...

A T-to-G change at position -3 in the acceptor splice site of IVS1 (TAG to GAG) was found in a Saudi Arabian patient with beta-plus-thalassemia (613985) by Wong et al. (1989). Indeed, Wong et al. (1989) identified 2 different nucleotide substitutions in consensus acceptor splice sequences of the beta-globin gene leading to beta-thalassemia. One was at the IVS1/exon 2 junction and the other at the IVS2/exon 3 junction (141900.0361). Both mutations were single nucleotide substitutions, T-to-G and C-to-A, at position -3 immediately adjacent to the invariant AG dinucleotide. For the IVS2/exon 3 mutation, abnormal splicing into the cryptic splice site at IVS2 nucleotide 579 was demonstrated.


.0363 BETA-PLUS-THALASSEMIA

HBB, IVS1, C-A, -8
  
RCV000016711...

A C-to-A change at position -8 in the acceptor splice site of IVS2 was found in an Algerian patient with beta-plus-thalassemia (613985) by Beldjord et al. (1988).


.0364 BETA-PLUS-THALASSEMIA

HBB, IVS1, G-A, +110
  
RCV000016712...

A G-to-A change at position 110 of IVS1 was found in a Mediterranean patient with beta-thalassemia (613985) by Spritz et al. (1981) and Westaway and Williamson (1981). The mutation created a new splice acceptor site.

Kaplan et al. (1990) studied the molecular basis of beta-thalassemia minor, which has a frequency of about 1% among French Canadians residing in Portneuf County of Quebec Province. They showed that there were 2 different beta-thalassemia mutations segregating in the population: an RNA processing mutation involving nucleotide 110 of IVS1 on haplotype 1 and a point mutation leading to chain termination through a nonsense codon at position 39 (141900.0312), occurring on haplotype 2.


.0365 BETA-ZERO-THALASSEMIA

HBB, IVS1, T-G, +116
  
RCV000016713...

A T-to-G change at position 116 of IVS1 in the HBB gene was found in a Mediterranean patient by Metherall et al. (1986). The mutation created a new acceptor splice site, which resulted in the inclusion of IVS1 sequences in mature mRNA, producing a frameshift within exon 2 and a termination codon 34 amino acids downstream from the abnormal splice.


.0366 BETA-PLUS-THALASSEMIA

HBB, IVS2, T-G, +705
  
RCV000016714...

A T-to-G change at position 705 of IVS2 was found in a Mediterranean patient with beta-plus-thalassemia (613985) by Dobkin et al. (1983). The mutation created a new acceptor splice site.


.0367 BETA-PLUS-THALASSEMIA

HBB, IVS2, C-G, +745
  
RCV000016715...

A C-to-G change at position 745 of IVS2 was found in a Mediterranean patient with beta-plus-thalassemia (613985) by Orkin et al. (1982). The mutation created a new acceptor splice site.


.0368 BETA-ZERO-THALASSEMIA

HBB, IVS2, C-T, +654
  
RCV000016716...

A C-to-T change at position 654 of IVS2 was found in a Chinese by Cheng et al. (1984).


.0369 BETA-PLUS-THALASSEMIA

HBB, GGT24GGA AND GLY24GLY
  
RCV000016717...

In an American black patient with beta-plus-thalassemia (613985), Goldsmith et al. (1983) found a change in codon 24 from GGT to GGA. Although silent in terms of changing the amino acid sequence, the mutation affected processing of mRNA.


.0370 BETA-PLUS-THALASSEMIA

HBB, -101C-T, PROMOTER
  
RCV000016719...

Gonzalez-Redondo et al. (1989) found a C-to-T change in nucleotide -101 in an asymptomatic Turkish carrier of beta-thalassemia. This is one of the transcriptional mutants causing beta-thalassemia. Ristaldi et al. (1990) showed that this mutation is a relatively frequent cause of beta-thalassemia in the Italian population, where it is always associated with haplotype 1. Compound heterozygosity for this promoter mutation and a mutation for severe beta-thalassemia results in a mild form of thalassemia intermedia (Murru et al., 1991). In studies of infants of Italian couples, 1 member of which was heterozygous for this promoter mutation, Murru et al. (1993) demonstrated that mutation leads to a more severe defect in beta-globin chain production in infancy than in adulthood. The moment of transition from the fetal-infant to the adult pattern of expression seems to be at about 2 years of age. This age-related pattern of expression had not been detected for other beta-thalassemia mutations. Assuming the existence of different distal CACCC box binding proteins with an activating function on the beta-globin gene promoter in fetal and adult ages, Murru et al. (1993) speculated that the fetal type interacts less efficiently with the mutated CACCC promoter as compared with the adult one. They suggested that the findings permit one to predict a mild phenotype even when HbA is absent in the newborn.

Maragoudaki et al. (1999) reported the clinical, hematologic, biosynthetic, and molecular data on 25 double heterozygote beta-thalassemia intermedia patients and 45 beta-thalassemia heterozygotes with the C-to-T substitution at nucleotide position -101 from the cap site, in the distal CACCC box of the HBB promoter. This mutation is considered the most common among the silent beta-thalassemia mutations in Mediterranean populations. Of the 25 compound heterozygotes for the promoter mutation and common severe beta-thalassemia mutations, all but 1 had mild thalassemia intermedia preserving hemoglobin levels around 9.5 g/dl and hemoglobin F levels less than 25%. Strict assessment of hematologic and biosynthetic findings in the heterozygotes for the promoter mutation demonstrated that less than half of them had completely normal (silent) hematology.


.0371 BETA-PLUS-THALASSEMIA

HBB, -92C-T
  
RCV000016720...

Kazazian (1990) found a C-to-T change at position -92 in a Mediterranean patient with beta-plus-thalassemia (613985).


.0372 BETA-PLUS-THALASSEMIA

HBB, -88C-T
  
RCV000016718...

Orkin et al. (1984) found a C-to-T change at position -88 in an American black and an Asiatic Indian with beta-plus-thalassemia (613985).


.0373 BETA-PLUS-THALASSEMIA

HBB, -88C-A
  
RCV000016721...

In a Kurdish Jew with beta-plus-thalassemia (613985), Rund et al. (1989, 1991) found a C-to-A change at position -88.


.0374 BETA-PLUS-THALASSEMIA

HBB, -87C-G
  
RCV000016722...

In a Mediterranean patient with beta-plus-thalassemia (613985), Orkin et al. (1982) found a C-to-G change at position -87.


.0375 BETA-PLUS-THALASSEMIA

HBB, -86C-G
  
RCV000016723...

In a Lebanese patient with beta-plus-thalassemia (613985), Kazazian (1990) found a C-to-G change at position -86.


.0376 BETA-PLUS-THALASSEMIA

HBB, -31A-G
  
RCV000016724...

In a Japanese patient with beta-plus-thalassemia (613985), Takihara et al. (1986) found an A-to-G change at position -31. Also see Yamashiro et al. (1989).


.0377 BETA-PLUS-THALASSEMIA

HBB, -30T-A, PROMOTER
  
RCV000016725...

In a Turkish patient with beta-plus-thalassemia (613985), Fei et al. (1988) found a T-to-A change at position -30 (a TATA box mutation). Fedorov et al. (1992) found the T-30A mutation in a Karachai patient with beta-thalassemia intermedia.


.0378 BETA-PLUS-THALASSEMIA

HBB, -30T-C, PROMOTER
  
RCV000016726...

In a Chinese with beta-plus-thalassemia (613985), Cai et al. (1989) demonstrated a new beta-thalassemia mutation: a T-to-C mutation at position -30 converting a normal TATA box sequence from ATAAA to ACAAA.


.0379 BETA-PLUS-THALASSEMIA

HBB, -29A-G, PROMOTER
  
RCV000016727...

An A-to-G change at position -29 (a TATA box mutation) was found in an American black by Antonarakis et al. (1984) and in a Chinese patient with beta-plus-thalassemia (613985) by Huang et al. (1986).


.0380 BETA-PLUS-THALASSEMIA

HBB, -28A-C, PROMOTER
  
RCV000016728...

In a Kurdish Jew with beta-plus-thalassemia (613985), Poncz et al. (1982) found an A-to-C change at position -28 (a TATA box mutation).


.0381 BETA-PLUS-THALASSEMIA

HBB, -28A-G, PROMOTER
  
RCV000016729...

In Chinese patient with beta-plus-thalassemia, Orkin et al. (1983) found an A-to-G change at position -28 (a TATA box mutation).


.0382 BETA-PLUS-THALASSEMIA

HBB, 3-UNT, T-C, +3
  
RCV000016730...

In an American black patient with beta-plus-thalassemia (613985), Orkin et al. (1985) found a change from AATAAA to AACAAA in the 3-prime untranslated portion of the gene. This and several others are RNA cleavage and polyadenylation mutants.


.0383 BETA-PLUS-THALASSEMIA

HBB, 3-UNT, A-G, +6
  
RCV000016731...

In a Kurdish patient with beta-plus-thalassemia (613985), Rund et al. (1989, 1991, 1992) found a change from AATAAA-to-AATAAG in the 3-prime untranslated portion of the gene. Rund et al. (1992) used this and another polyadenylation mutation (141900.0417) to investigate the function of the poly(A) signal in vivo and to evaluate the mechanism whereby these mutations lead to a thalassemic phenotype. Analysis of RNA derived from peripheral blood demonstrated the presence of elongated RNA species in patients carrying either mutation. Other aspects of RNA processing (initiation, splicing) were unimpaired.


.0384 BETA-PLUS-THALASSEMIA

HBB, 3-UNT, A DEL, +4
   RCV000016732

In an Arab patient with beta-plus-thalassemia (613985), Kazazian (1990) found deletion of an A in the 3-prime RNA cleavage-polyadenylation signal, i.e., a change from AATAAA to AATAA.


.0385 BETA-PLUS-THALASSEMIA

HBB, 3-UNT, G INS, +4
   RCV000016733

In a Mediterranean patient with beta-plus-thalassemia (613985), Jankovic et al. (1989) found a change from AATAA to AATGAA in the RNA cleavage-polyadenylation signal.


.0386 BETA-PLUS-THALASSEMIA

HBB, 3-UNT, A-G, +5
  
RCV000016734

In a Malaysian patient with beta-plus-thalassemia (613985), Jankovic et al. (1989) found a change from AATAAA to AATAGA in the RNA cleavage-polyadenylation signal.


.0387 BETA-PLUS-THALASSEMIA

HBB, CAP, A-C
  
RCV000029957...

In an Asian Indian patient with beta-plus-thalassemia (613985), Wong et al. (1986) found a cap site mutation, specifically, an A-to-C change at position 1. The first nucleotide of the transcript is designated the cap site; it is usually 60-100 nucleotides 5-prime of the initiator methionine codon in the untranslated part of the transcript. The cap site is the nucleotide to which a 7-methyl-G cap is added to the mRNA transcript. The mutation reported by Wong et al. (1987) is the only cap site mutation reported to date (Kazazian, 1992).


.0388 MOVED TO 141900.0356


.0389 HEMOGLOBIN BIRMINGHAM

HBB, 9-BP DEL
  
RCV000016736

Wilson et al. (1990) found loss of leu-ala-his-lys at positions 141, 142, 143, and 144 and their replacement by a gln residue. The changes were the result of a deletion of 9 nucleotides, namely, 2 bp of codon 141, all of codons 142 and 143, and 1 bp of codon 144; the remaining CAG triplet (C from codon 141 and AG from codon 144) codes for the inserted glutamine.


.0390 HEMOGLOBIN GALICIA

HBB, 3-BP DEL
  
RCV000016737

In a Spanish patient, Wilson et al. (1990) found that his and val at positions 97 and 98 of the beta-chain had been replaced by a leu residue. The change resulted from the deletion of ACG in codons 97 and 98 and the creation of a remaining triplet CTG (C from codon 97 and TG from codon 98) which codes for the inserted leucine residue. Wilson et al. (1990) considered 2 mechanisms, namely, slipped mispairing in the presence of short repeats, and misreading by DNA polymerase due to a local distortion of the DNA helix, as the basis for the small deletions in hemoglobin Birmingham and hemoglobin Galicia.


.0391 HEMOGLOBIN SOUTH MILWAUKEE

HBB, LEU105PHE
  
RCV000016738...

In 4 generations of a family of English ancestry, Honig et al. (1990) found 15 persons with erythrocytosis. Elevated hemoglobin levels were accompanied by leftward-shifted whole blood oxygen equilibrium curves. Phlebotomies for relief of symptoms attributable to erythrocytosis had been necessary in 5 of the affected family members. In the affected individuals, 43% of the beta chains contained a leucine-to-phenylalanine substitution at position 105. Oxygen equilibrium curves demonstrated normal Bohr effect but decreased cooperativity.


.0392 BETA-ZERO-THALASSEMIA

HBB, IVS1, T-A, +2
  
RCV000016739...

Bouhass et al. (1990) described an Algerian patient with beta-zero-thalassemia (613985) who was a genetic compound for the mutation listed as 141900.0327 and a new mutation consisting of a T-to-A transversion at position 2 of IVS1.


.0393 HEMOGLOBIN DHONBURI

HEMOGLOBIN NEAPOLIS
HBB, VAL126GLY
  
RCV000016741...

While investigating the mechanism of a beta-thalassemia intermedia phenotype in a 34-year-old Thai male, Bardakdjian-Michau et al. (1990) discovered a new beta-hemoglobin variant, val126-to-gly, which they called Hb Dhonburi. The variant was unstable but exhibited normal oxygen-binding properties. Pagano et al. (1991) found the same amino acid substitution in 3 unrelated families from southern Italy and dubbed it Neapolis. A GTG-to-GGG mutation was responsible for the change. The 8 heterozygous patients showed hematologic and biosynthetic alterations of mild beta-thalassemia. The characteristics were very similar to those of Hb E (141900.0071), Hb Knossos (141900.0149), and Hb Malay (141900.0168), all of which have a single base substitution causing amino acid replacement and alternative splicing of the precursor beta-mRNA by activating cryptic donor sites in exon 1.

Moghimi et al. (2004) demonstrated this variant in a family from northern Iran.


.0394 HEMOGLOBIN IOWA

HBB, GLY119ALA
  
RCV000016743

Plaseska et al. (1990) found a gly-to-ala mutation at position beta119 in a black infant and her mother. The baby was also heterozygous for Hb S (141900.0243). The change in hemoglobin Iowa did not affect stability or oxygen-carrying properties; hematologic data were normal in the mother and child.

Somjee et al. (2004) described Hb Iowa in compound heterozygous state, not with Hb S as in the initial report, but with Hb C (141900.0038). The patient was an African American girl, originally diagnosed as homozygous Hb C during neonatal screening. Both cases indicated that there were no abnormal hematologic manifestations associated with this rare hemoglobin variant. However, in both cases, Hb Iowa was mistaken for Hb F during routine neonatal screening. Neonatal misidentification of Hb Iowa led to misdiagnosis of sickle cell disease in the patient of Plaseska et al. (1990) and Hb C in the patient of Somjee et al. (2004).


.0395 BETA-THALASSEMIA

HBB, 1-BP INS, A, CODON 47
  
RCV000016744...

In a Suriname carrier of beta-thalassemia (613985), Losekoot et al. (1990) detected a frameshift insertion in the HBB gene: a single nucleotide (+A) at codon 47 which caused the formation of a termination codon at position 52.


.0396 HEMOGLOBIN CALAIS

HBB, ALA76PRO
  
RCV000016740

In a 43-year-old woman suffering from chronic anemia since the age of 20, Wajcman et al. (1991) found this new hemoglobin variant which displays decreased oxygen affinity.


.0397 HEMOGLOBIN ZENGCHENG

HBB, LEU114MET
  
RCV000016486...

This variant was detected in a cord blood sample from a Chinese newborn tested by IEF and reversed phase high performance liquid chromatography (Plaseska et al., 1990). This mutation occurs with another mutation in Hb Masuda (141900.0172).


.0398 HEMOGLOBIN TERRE HAUTE

BETA-PLUS-THALASSEMIA
HBB, LEU106ARG
  
RCV000016746...

Adams et al. (1978, 1979) described a hemoglobin variant responsible for severe beta-thalassemia with dominant inheritance. They concluded that the mutation, which they referred to as Hb Indianapolis (see 141900.0117), carried a cys112-to-arg mutation. Subsequent description of 2 families, which indeed carried this mutation but were minimally affected, prompted restudy of the original family. Both of the original carriers of the variants had succumbed to their severe anemia. However, by the use of PCR, enough DNA was recovered from a 10-year-old bone marrow microscope slide to sequence the third exon of the beta-globin gene. These studies showed substitution of arginine for leucine at position 106 of the beta-globin chain. In order to avoid confusion with the cys112-to-arg mutation, to which the name Hb Indianapolis was firmly attached, Coleman et al. (1991) renamed the original variant hemoglobin Hb Terre Haute. The dominantly inherited beta-thalassemias that are due to highly unstable variant beta chains, such as HB Indianapolis, result from the rapid catabolism of the beta chains and consequent erythroblast destruction within the bone marrow. These differ from the classic unstable hemoglobin variants in which most damage occurs to erythrocytes in the circulation, resulting in hemolytic anemia rather than impaired erythropoiesis.


.0399 BETA-PLUS-THALASSEMIA

HBB, 3-UNT, A-G, +4
  
RCV000016748...

In a Dutch patient with a mild, nontransfusion dependent beta-thalassemia phenotype (613985), Losekoot et al. (1991) found a mutation in the cleavage-polyadenylation sequence. The mutation, AATAAA-to-AATGAA, was detected using denaturing gradient gel electrophoresis (DGGE) and direct sequencing of genomic DNA amplified by PCR.


.0400 HEMOGLOBIN VALLETTA

HBB, THR87PRO
  
RCV000016749...

Kutlar et al. (1991) described a new hemoglobin variant called Hb Valletta, which is characterized by a threonine-to-proline substitution at position 87 of the beta chain. This mutation was found to be linked to that of the gamma-chain variant Hb F-Malta-I (142250.0014) which has a his-to-arg mutation at position 117 of the G-gamma chain. The 2 genes are 27 to 28 kb apart. No chromosomes with one or the other mutation alone were identified.


.0401 HEMOGLOBIN JACKSONVILLE

HBB, VAL54ASP
  
RCV000016750

In a 12-year-old black male with splenomegaly and anemia, Gaudry et al. (1990) found a hemoglobin variant manifest by electrophoretic abnormality. This unstable hemoglobin was found to have a substitution of aspartic acid for valine at position 54 of the beta chain.


.0402 HEMOGLOBIN CHESTERFIELD

HBB, LEU28ARG
  
RCV000016751

Thein et al. (1991) reported a patient with severe heterozygous beta-thalassemia characterized by large inclusion bodies and resulting in a single base substitution, CTG to CGG, in codon 28 in exon 1. The mutant hemoglobin, called Hb Chesterfield, had an unstable beta chain. The patient was a 34-year-old English woman who had presented at the age of 7 years with abdominal pain, anemia, jaundice, and hepatosplenomegaly. She had been transfusion-dependent since the age of 10. Because of increasing transfusion requirements, a splenectomy was performed at the age of 13. Cholecystectomy was required at the age of 28.


.0403 HEMOGLOBIN QUEBEC-CHORI

HEMOGLOBIN CHORI
HBB, THR87ILE
  
RCV000016753

Witkowska et al. (1991) found that sickle cell disease in a 3-year-old girl was due to compound heterozygosity for the Hb S gene and a new mutation called Hb Quebec-Chori. ('Chori' is an acronym for the Children's Hospital Oakland Research Institute.) Although the purified variant had gelling properties similar to those of Hb A, a mixture of it with Hb S resulted in a delay time of polymerization very similar to that of a homogeneous solution of Hb S. The sickle gene was inherited from the father, who was black and originally from Guyana. The new mutant was inherited from the mother, who was white and of English-Irish-French Canadian extraction. By peptide analysis, the new hemoglobin was found to have substitution of isoleucine for threonine-87.


.0404 HEMOGLOBIN REDONDO

HEMOGLOBIN ISEHARA
HBB, HIS92ASN-TO-ASP
  
RCV000016756

In a Portuguese patient suffering from a chronic hemolytic anemia, Wajcman et al. (1991) found an unstable hemoglobin which contained a his92-to-asn substitution. The variant readily loses its heme group and a rapid deamidation occurs in vitro, yielding an asp92 semihemoglobin. The oxygen affinity of the patient's red blood cells was increased, leading to stimulation of erythropoiesis and a macrocytic hemolytic disease. Harano et al. (1991) found the same unstable hemoglobin variant in a Japanese female with hemolytic anemia and called it Hb Isehara.

In addition to Hb Redondo, 6 other rare Hb variants had been reported in which deamidation of an asn residue to an asp occurred as a spontaneous posttranslational modification: Hb J (Sardegna) (141850.0036), Hb J (Singapore) (141800.0075), Hb La Roche-sur-Yon (141900.0482), Hb Osler (141900.0211), Hb Providence (141900.0227), and Hb Wayne (141850.0004).


.0405 HEMOGLOBIN COIMBRA

HBB, ASP99GLU
  
RCV000016757

In a Portuguese family living in Coimbra, Portugal, Tamagnini et al. (1991) identified a high oxygen affinity hemoglobin variant. Aspartic acid at residue 99 was replaced by glutamic acid in the beta chain. Two affected members had erythrocytosis with hemoglobin levels of 18 to 20 g/dl. A GAT-to-GAA mutation at codon 99 represented the seventh type of substitution at this specific location. From a survey of mutations, Tamagnini et al. (1991) suggested that codons GAC(asp), GAT(asp), GAG(glu), and GAA(glu) are particularly susceptible to mutational events.


.0406 BETA-PLUS-THALASSEMIA

HBB, -32C-A, PROMOTER
  
RCV000016752...

Lin et al. (1992) described a mutation in the TATA box that has the sequence CATAAA and is located about 30 nucleotides upstream of the cap site. The mutation changed CATAAA to AATAAA.


.0407 HEMOGLOBIN CLEVELAND

HBB, CYS93ARG AND GLU121GLN
  
RCV000016317...

See Wilson et al. (1991). This hemoglobin variant combines the mutations present in Hb D (glu121-to-gln; 141900.0065) and in Hb Okazaki (cys93-to-arg; 141900.0207).


.0408 HEMOGLOBIN GRENOBLE

HBB, PRO51SER AND ASP52ASN
  
RCV000016537...

See Lacombe et al. (1990). The asp52-to-asn mutation is also found in Hb Osu Christiansborg (141900.0212).


.0409 HEMOGLOBIN KODAIRA

HBB, HIS146GLN
  
RCV000016760

This abnormal hemoglobin was discovered in a 75-year-old Japanese male with an unusually low level of Hb A(1c) (Harano et al. (1990, 1992)). The patient was being treated for chronic renal failure. A CAC-to-CAA change in codon 146 was responsible for substitution of glutamine for histidine. Hb Kodaira was the fifth hemoglobin variant involving the terminal codon of the beta chain. The others are Hb Hiroshima (141900.0110), Hb York (141900.0305), Hb Cowtown (141900.0056), and Hb Cochin-Port Royal (141900.0051).


.0410 HEMOGLOBIN MONTREAL

HBB, 9-BP DEL AND 12-BP INS
   RCV000016761

Plaseska et al. (1991) described a new variant with a beta chain 1 residue longer than the normal as a result of the deletion of asp, gly, and leu at positions 73, 74, and 75 and the insertion of ala, arg, cys, and gln in their place. Hb Montreal is unstable.


.0411 HEMOGLOBIN NIKOSIA

HBB, LYS17GLN
  
RCV000016762

.0412 HEMOGLOBIN ST. FRANCIS

HBB, GLU121GLY
  
RCV000016763

See Abourzik et al. (1991). This mutation is at the same nucleotide as that in Hb D (Los Angeles) (141900.0065).


.0413 HEMOGLOBIN YAHATA

HBB, CYS112TYR
  
RCV000016764

.0414 HEMOGLOBIN RANCHO MIRAGE

HBB, HIS143ASP
  
RCV000016765

A variant hemoglobin resulting from substitution of aspartic acid for histidine at residue 143 of the beta chain was detected in a 17-year-old male who had mild anemia (Moo-Penn et al., 1992).


.0415 BETA-ZERO-THALASSEMIA

HBB, GLU90TER
  
RCV000016766...

In affected members in a Japanese family with beta-zero-thalassemia (613985), Hattori et al. (1992) found a GAG-to-TAG change in codon 90, substituting a stop codon for glutamic acid. The mutation had previously been found only in Japanese, the first case having been reported by Harano et al. (1989).


.0416 BETA-ZERO-THALASSEMIA

HBB, IVS2AS, -3, C-G
  
RCV000016767...

Hattori et al. (1992) identified this mutation in a Japanese patient with beta-zero-thalassemia (613985). The abnormality was a substitution of guanine for cytosine at nucleotide 848 of IVS2. This nucleotide is at position -3 in the acceptor splice sequence. A C-to-A mutation at the same site in an Iranian patient had been reported by Wong et al. (1989); see 141900.0362.


.0417 BETA-PLUS-THALASSEMIA

HBB, 3-NT, 5-BP DEL, AATAAA-A
  
RCV000016768...

Rund et al. (1992) used a polyadenylation mutation involving the deletion of 5-bp (AATAAA-to-A) and another mutation (141900.0383) to study the function of the poly(A) signal in vivo and to evaluate the mechanism whereby polyadenylation mutations lead to a thalassemic phenotype.


.0418 BETA-ZERO-THALASSEMIA

HBB, IVS1AS, G-C, -1
  
RCV000016769...

In a Sicilian subject with beta-zero-thalassemia (613985), Renda et al. (1992) identified a G-C substitution in the invariant AG dinucleotide at the acceptor splice site of the first intron. In the same nucleotide, a G-A substitution is a frequent cause of beta-zero-thalassemia in Egyptians (see 141900.0356). Although mutations in the invariant GT or AG dinucleotide splice junctions are known to give rise to beta-zero-thalassemia, studies were not performed in the specific patient reported by Renda et al. (1992) to determine that this was in fact a beta-zero-thalassemia mutation.


.0419 BETA-ZERO-THALASSEMIA

HBB, 1-BP DEL, GTG-TG
  
RCV000016770...

In 3 out of 3,000 beta-thalassemia (613985) chromosomes in the Sardinian population, Rosatelli et al. (1992) found deletion of a single nucleotide G at codon 1 (GTG-to-TG), which resulted in both a frameshift and the formation of an in phase termination codon at codon 3. In addition, sequencing showed at codon 2 of the globin gene a single nucleotide substitution, C to T, which is a common silent substitution in the Mediterranean population (Orkin et al., 1982).


.0420 HEMOGLOBIN MUSCAT

HBB, LEU32VAL
  
RCV000016771

In 2 members of an Arabian family from Oman, Ramachandran et al. (1992) discovered a leu-to-val replacement at position beta-32 by reversed phase high performance liquid chromatography. In 1 person, it occurred with Hb S and in the other with Hb A. Although Hb Muscat was slightly unstable, its presence had no apparent adverse effect on the health of its carriers.


.0421 HEMOGLOBIN BAB-SAADOUN

HBB, LEU48PRO
  
RCV000016772

In a young Arabian boy living in Tunisia, Molchanova et al. (1992) detected a leu48-to-pro substitution in the beta chain. Since the parents did not have the variant, it presumably occurred by spontaneous mutation. It was thought not to be the cause of hemolytic anemia.


.0422 HEMOGLOBIN MANHATTAN

HBB, 1-BP DEL, -G, CODON 109
  
RCV000016687...

As alleles of the HBB gene producing beta-thalassemia were discovered, it became evident that there is a relative paucity of beta-thalassemia mutations in exon 3 of HBB even though this exon accounts for about 30% of the coding region. It appears to be a general rule that 1-bp frameshift mutations and nonsense mutations early in exon 3 produce a chronic hemolytic anemia in the heterozygous state. On the other hand, mutations of this type in exons 1 and 2 in the heterozygous state produce beta-thalassemia trait with mild phenotypic deviations from the normal. Kazazian et al. (1992) reported another example of this rule: in a 78-year-old Lithuanian Ashkenazi Jew with chronic hemolytic anemia, they demonstrated a -1 frameshift (-G) in codon 109. The globin was termed beta-Manhattan for the site of residence of the patient.


.0423 BETA-ZERO-THALASSEMIA

HBB, IVS2, G-C, -1
  
RCV000016774...

In 4 members of a Yugoslavian family who exhibited severe microcytosis and hypochromic anemia (613985), Jankovic et al. (1992) found heterozygosity for a G-C mutation in the last nucleotide of IVS2. This change of the invariant AG dinucleotide of the acceptor splice site of intron 2 abolished normal splicing. Two other mutations of the IVS2 acceptor splice site have been identified as causes of beta-zero thalassemia; see 141900.0353 and 141900.0354.


.0424 BETA-THALASSEMIA INTERMEDIA

HEMOGLOBIN BRESCIA
HEMOGLOBIN DURHAM-N.C.
HBB, LEU114PRO
  
RCV000016775...

In a family of northern Italian descent (Brescia-Lombardia), Murru et al. (1992) found that a 14-year-old girl with the clinical phenotype of severe thalassemia intermedia (613985) had a heterozygous CTG-to-CCG change at codon 114 resulting in substitution of proline for leucine in the beta-globin chain. The resulting hemoglobin tetramer was highly unstable and precipitated to form inclusion bodies in peripheral red blood cells. The unusually severe phenotype present in this heterozygote was thought to be explained by the coinheritance of a triple alpha-globin locus.

In a 29-year-old female of Irish descent with thalassemia-like anemia during her first pregnancy, deCastro et al. (1992) found no gross structural alteration on Southern blot analysis of the globin genes but found an alpha:beta globin chain synthesis ratio of 0.91 (control = 0.94). Because they suspected an unstable hemoglobinopathy and because many of these disorders are due to point mutations in exon 3 of the beta-globin chain, they performed PCR-SSCP analysis, which showed an abnormality. Sequencing demonstrated a T-to-C transition at codon 114 resulting in a leucine-to-proline substitution. They called the hemoglobin variant Durham-N.C. to distinguish it from hemoglobin Durham, named for the city in England. The mutation created a novel MspI restriction site in exon 3 of the HBB gene. De Castro et al. (1994) demonstrated that this hemoglobinopathy, like several others within exon 3 of the beta-globin gene, e.g., Hb Showa-Yakushiji (leu110-to-pro; 141900.0262), result in a thalassemic and/or hemolytic phenotype with moderately severe microcytic anemia inherited as an autosomal dominant.

Kim et al. (2001) described the molecular and hematologic characteristics of a Korean family with a dominantly inherited beta-thalassemia. Carriers were characterized by moderate anemia, hypochromia, microcytosis, elevated Hb A2 and Hb F levels, and splenomegaly. A CTG (leu) to CCG (pro) change at codon 114 of the HBB was demonstrated. They referred to the abnormal hemoglobin as Hb Durham-N.C./Brescia.


.0425 BETA-PLUS-THALASSEMIA

HBB, -90C-T, PROMOTER
  
RCV000016778...

In an asymptomatic Portuguese female with beta-plua-thalassemia (613985), Faustino et al. (1992) found heterozygosity for a C-to-T transition at position -90 in the proximal CACCC box.


.0426 BETA-THALASSEMIA INTERMEDIA, DOMINANT

HBB, IVS2DS, 2-BP DEL, AG
  
RCV000016779...

In a Portuguese family with 'dominant' beta-thalassemia intermedia (613985), Faustino et al. (1992) found deletion of nucleotides 4 and 5 (AG) in IVS2 of the HBB gene, converting GTGAGT to GTGTCT.

In a 5-generation Portuguese family, Faustino et al. (1998) described an autosomal dominant form of beta-thalassemia intermedia. Carriers showed moderate anemia, hypochromia, microcytosis, elevated Hb A2 and Hb F, splenomegaly, hepatomegaly, and inclusion bodies in peripheral red blood cells after splenectomy. The molecular basis was found to be deletion of 2 nucleotides, AG, within the 5-prime splice site consensus sequence of intron 2 of the HBB gene. The fourth and fifth nucleotides in the sequence GTGAG were deleted. Reticulocyte RNA studies performed by RT-PCR and primary extension analysis showed 3 abnormally processed transcripts, which, upon sequencing, were shown to correspond to (1) skipping of exon 2, and (2) activation of 2 cryptic splice sites (between codons 59 and 60), and at nucleotide 47 in the second intron. In vitro translation studies showed that at least 1 of these aberrant mRNA species is translated into an abnormally elongated peptide whose cytotoxic properties could, in part, be causing the atypical dominant mode of inheritance observed in this family. Faustino et al. (1998) suggested that this elongated beta chain is unable to combine with an alpha-globin chain to form a functional hemoglobin molecule. Its degradation would, then, exhaust the proteolytic defense mechanism of the erythroid precursors, leading to inefficient proteolysis of the free alpha chains in excess.


.0427 HEMOGLOBIN DUINO

HBB, HIS92PRO AND ARG104SER
  
RCV000016293...

Wajcman et al. (1992) demonstrated that Hb Duino, an unstable hemoglobin, carries 2 point mutations, the his92-to-pro mutation of Hb Newcastle (141900.0197) and the arg104-to-ser mutation of Hb Camperdown (141900.0042). Family studies demonstrated that the Hb Newcastle abnormality was a de novo mutation of a gene already carrying the Hb Camperdown substitution. One member of the Italian family studied by Wajcman et al. (1992) had hemolytic anemia.


.0428 HEMOGLOBIN BADEN

HBB, VAL18MET
  
RCV000016781

Divoky et al. (1992) analyzed the hemoglobin of a child of German descent living in the former German Democratic Republic and exhibiting typical clinical features of beta-thalassemia intermedia. One of his chromosomes 11 and 1 of his mother's carried a GTG-to-ATG mutation at codon 18, resulting in the replacement of a valine residue by a methionine residue. Called Hb Baden, the newly discovered beta-chain variant represented only 2 to 3% of the hemoglobin in both the patient and his mother because of the presence of an IVS1 +5 G-to-C thalassemic mutation (141900.0357) on the same chromosome. On the other chromosome, inherited from the father, the boy carried the val126-to-gly mutation of Hb Dhonburi (141900.0393), which itself is slightly unstable and associated with mild thalassemic features.


.0429 HEMOGLOBIN GRAZ

HBB, HIS2LEU
  
RCV000016782

Liu et al. (1992) accidentally detected 2 abnormal hemoglobins by cation exchange high performance liquid chromatography performed with an automated system designed to quantitate Hb A1c in blood samples from patients with diabetes mellitus. The variants eluted together with the fast-moving Hb A1c. One of the variants, found in 4 healthy, apparently unrelated adults, involved a change from a histidine to a leucine residue at position 2 of the beta chain. The second variant was identical to Hb Sherwood Forest (141900.0261).


.0430 BETA-ZERO-THALASSEMIA

HBB, MET1ILE
  
RCV000016783...

In a typical beta-thalassemia (613985) carrier of Italian descent, Saba et al. (1992) demonstrated a G-to-A transition in the initiation codon of the HBB gene, producing a substitution of isoleucine for methionine. The absence of the initiation methionine led to defective beta-globin mRNA translation and probably determined the complete absence of beta-chain production. Indeed, initiation of translation may have occurred at the first downstream ATG sequence, which is located at codon 21-22; the resulting out-of-frame reading probably terminates at the new UGA termination codon at codon 60-61. Initiation codon mutations previously described in both the alpha (141850.0022) and beta (141900.0344) globin genes all result in complete inactivation of the affected globin gene.

In 7 members of 3 generations of a family living in northern Sweden, Landin et al. (1995) found an initiation codon mutation ATG-to-ATA of the HBB gene. The mutation changed the initiation codon from methionine to isoleucine and resulted in a beta-zero-thalassemic phenotype. The affected family members all presented hematologic findings typical for the beta-thalassemic trait, with slight anemia, marked microcytosis, and increased levels of Hb A2. See 141900.0345 for an initiation codon mutation ATG-to-ACG, which changes methionine to threonine.


.0431 HEMOGLOBIN KARLSKOGA

HBB, ASP21HIS
  
RCV000016784

In the course of quantification of Hb A(1c) in a 48-year-old Swedish woman, Landin (1993) discovered a variant hemoglobin that comprised approximately 39% of the total hemoglobin. A study demonstrated a GAT-to-CAT mutation in codon 21, corresponding to an asp21-to-his substitution. As predicted from the location of the substitution in the molecule, it was not associated with any overt hematologic abnormalities.


.0432 HEMOGLOBIN MUSKEGON

HBB, GLY83ARG
  
RCV000016785...

During a routine hematologic evaluation of a 1-year-old boy and his father, Broxson et al. (1993) found a variant hemoglobin that produced a band on electrophoresis in the same position as that for sickle hemoglobin. Screening of other family members showed that the paternal grandmother and an uncle also had the variant. Amino acid analysis demonstrated that glycine at position 83 of the beta-globin chain had been substituted by arginine. This gly83 is an external residue with no significant inter- or intra-molecular contacts, and mutation at this residue would not be expected to cause any changes in the functional properties of the variant.


.0433 HEMOGLOBIN TIGRAYE

HBB, ASP79HIS
  
RCV000016786...

In a healthy 36-year-old male of Ethiopian descent with normal hematologic findings, Molchanova et al. (1993) found a hemoglobin variant with electrophoretic mobility on cellulose acetate like that of Hb S. DNA studies demonstrated a GAC-to-CAC transversion leading to an asp79-to-his amino acid substitution.

Pistidda et al. (2001) identified the same mutation in a Caucasian in the Sassari district of Sardinia.


.0434 REMOVED FROM DATABASE


.0435 HEMOGLOBIN SARREBOURG

HBB, GLN131ARG
  
RCV000016787

Duwig et al. (1987) found a new unstable hemoglobin in a boy of 9 years hospitalized for hematuria and diffuse pains. Clinical examination demonstrated isolated splenomegaly without hepatomegaly or adenopathy. He was anemic and the variant hemoglobin constituted 30% of total hemoglobin. Molecular studies revealed a substitution of arginine for glutamine-131.


.0436 HEMOGLOBIN SAINT NAZAIRE

HBB, PHE103ILE
  
RCV000016788

In 4 apparently unrelated French families, Wajcman et al. (1993) found 5 patients carrying a hemoglobin variant associated with moderate erythrocytosis. The structural abnormality was a replacement of phenylalanine-103 by isoleucine. The residue involved was the same as that in Hb Heathrow (141900.0102), which is a phe103-to-leu substitution. The increase in oxygen affinity is much lower in Hb Saint Nazaire than in Hb Heathrow. The replacement of phenylalanine G5, which is located within the heme pocket, by leucine abolishes several contacts between heme and globin and leads to an environment of the heme with similarities to that observed in myoglobin. In contrast, the replacement of G5 by an isoleucine is likely to introduce less structural modifications.


.0437 HEMOGLOBIN HRADEC KRALOVE

HEMOGLOBIN HK
HBB, ALA115ASP
  
RCV000016791...

In a Czech family, Divoky et al. (1993) found a GCC-to-GAC mutation in codon 115 of the beta-globin gene as the cause of dominant beta-thalassemia trait. The variant hemoglobin was markedly unstable. A mother and daughter, who were heterozygotes, showed moderate anemia, reticulocytosis, nucleated red cells, target cells, Heinz body formation, and splenomegaly. Both had marked increase in fetal hemoglobin synthesis.


.0438 HEMOGLOBIN MANUKAU

HBB, VAL67GLY
  
RCV000016792...

Fay et al. (1993) described hemoglobin Manukau in 2 brothers presenting with nonspherocytic hemolytic anemia who became transfusion-dependent by 6 months of age. The severity of clinical expression seemed to be modulated by coexisting alpha-thalassemia. The brothers had a Niuean mother and a New Zealand Maori father. A second unusual feature was a modification of beta-141 leu, which appeared to be deleted because posttranslational modification had changed leu-141 to a residue (probably hydroxyleucine) that was not detected by standard amino acid analysis and sequencing methods. The same feature occurs in Hb Coventry (141900.0055).


.0439 HEMOGLOBIN VILLAVERDE

HBB, SER89THR
  
RCV000016793

In a 41-year-old man in Spain with severe erythrocytosis, Wajcman et al. (1993) found an electrophoretically silent hemoglobin variant with very high oxygen affinity and markedly reduced cooperativity. The structural abnormality was determined by mixing normal and abnormal beta chains, isolating the abnormal tryptic peptide by reversed-phase HPLC, and sequencing the peptide by mass spectrometry. Serine-89 was replaced by threonine.


.0440 HEMOGLOBIN HOWICK

HBB, TRP37GLY
  
RCV000016794

During routine hematologic investigation of a 44-year-old man, Owen et al. (1993) found a novel hemoglobin with high oxygen affinity and a substitution of glycine for tryptophan-37. This change would be expected to result in a destabilization of the deoxyhemoglobin form because of the reduced number of hydrogen bonds, salt bridges, and van der Waal contacts between the alpha-1 and beta-2 chains. Hemoglobin was 16.3 g/dL. The variant constituted 29% of the hemoglobin, indicating either reduced stability of the nascent Hb Howick chain or an impaired expression level.


.0441 HEMOGLOBIN DENVER

HBB, PHE41SER
  
RCV000016795...

Stabler et al. (1994) reported a 16-year-old white boy from Denver, Colorado, in whom cyanosis of the skin, lips, mucous membranes, conjunctivas, and nail beds was noted at the time of a dental extraction. The mother also had lifelong cyanosis and, although asymptomatic, had had severe anemia during pregnancy. The maternal grandmother and maternal aunt had chronic cyanosis and mild anemia. No abnormal hemoglobin band separate from that of hemoglobin A was found on electrophoresis, HPLC, and isoelectric focusing. However, a heat test showed hemoglobin instability, and O2 studies disclosed an appreciably right-shifted dissociation curve. On chromatography, the new variant--hemoglobin Denver--was found to carry a substitution of serine for phenylalanine at position 41 in the beta chain. In addition to reduction in O2 affinity, hemoglobin Denver was accompanied by moderate reticulocytosis and mild anemia. The corresponding substitution in the hemoglobin gamma gene is found in hemoglobin F (Cincinnati) (HBG2; 142250.0041) and is associated with cyanosis.


.0442 HEMOGLOBIN BECKMAN

HBB, ALA135GLU
  
RCV000016796

Rahbar et al. (1991) discovered Hb Beckman, an alanine-to-glutamic acid mutation at position 135 of the HBB gene, in a 32-year-old African American woman with chronic anemia and microcytosis and a palpable spleen. While substitution of proline at position 135 (Hb Altdorf; 141900.0007) results in an unstable hemoglobin variant with increased affinity for oxygen, substitution of glutamic acid has a reverse effect, i.e., Hb Beckman has reduced oxygen affinity.


.0443 HEMOGLOBIN KOREA

HBB, VAL33DEL OR VAL34DEL
  
RCV000016797

A de novo mutation was reported by Park et al. (1991) in an 8-year-old boy who presented with symptoms of mild anemia and was found to be icteric with moderate splenomegaly. PCR followed by DNA sequencing of the HBB gene demonstrated that the mutation results in a deletion of valine (GGT) at amino acid position 33 or 34 without altering the reading frame in the remainder of the subunit. The deletion appears to disrupt the globin structure badly, producing a clinical phenotype of beta-thalassaemia resembling that of an ineffective erythropoiesis.


.0444 MOVED TO 141900.0452


.0445 HEMOGLOBIN D (NEATH)

HBB, GLU121ALA
  
RCV000016799

During the course of a genetic survey of the first-year students at a London Medical School, Hb D (Neath) was discovered in an 18-year-old Caucasian female by Welch and Bateman (1993). In the variant HBB chain, the glutamic acid residue at position 121 is replaced with alanine.


.0446 HEMOGLOBIN WASHTENAW

HBB, VAL11PHE
  
RCV000016800...

Krishnan et al. (1993, 1994) reported a val-to-phe mutation at position 11 of the HBB chain in 6 members in 3 generations of a family of Hungarian-American descent. The proband had primary pulmonary hypertension, and other members of the family were mildly anemic. At least one other Hb variant, Hb Warsaw (141900.0257), has been reported to be associated with pulmonary hypertension. Hb Washtenaw is slightly unstable and has a low oxygen affinity.


.0447 HEMOGLOBIN ALESHA

HBB, VAL67MET
  
RCV000016276...

Molchanova et al. (1993) discovered Hb Alesha in a 15-year-old Russian patient with severe hemolytic disease, anemia, splenomegaly, Heinz body formation, and continued requirement for blood transfusions despite a splenectomy at age 3. PCR amplification and sequence analysis of the hemoglobin beta gene indicated a GTG-to-ATG point mutation at codon 67, causing a valine-to-methionine transition. Molchanova et al. (1993) postulated that the replacement of valine by the larger methionyl residue significantly reduces the stability of the hemoglobin molecule by disrupting the apolar bonds between the valine and the heme group.


.0448 HEMOGLOBIN DIEPPE

HBB, GLN127ARG
  
RCV000016802...

Girodon et al. (1992) reported Hb Dieppe in a 31-year-old French female with chronic anemia. DNA sequencing revealed a missense mutation (GAG-to-CGG) at position 127 of the beta-globin gene, causing a glutamine-to-arginine transition. The hemoglobin variant is highly unstable; the introduction of a positively charged hydrophilic residue at position 127 disrupts the tight contacts between the alpha and beta subunits.


.0449 HEMOGLOBIN HIGASHITOCHIGI

HEMOGLOBIN HT
HBB, GLY24DEL OR GLY25DEL
  
RCV000016803...

Hb Higashitochigi was discovered by Fujisawa et al. (1993) in a 2-year-old Japanese boy with chronic cyanosis. The variant is missing a glycine residue, due to a deletion of 3 nucleotides in the genomic DNA (codons 24-25: GGTGGT-to-GGT). It is likely that the absence of glycine indirectly distorts the heme pocket, causing decreased oxygen binding of the beta chain and impaired oxygen release of the normal alpha chain in the tetrameric molecule.


.0450 HEMOGLOBIN TROLLHAETTAN

HBB, VAL20GLU
  
RCV000016805

Landin et al. (1994) added another example to the more than 40 hemoglobin variants with increased oxygen affinity associated with erythrocytosis. In 3 generations of the family of a 23-year-old male from Trollhaettan in Sweden, Landin et al. (1994) observed heterozygosity for a GTG-to-GAG transition at codon 20 that predicted a val-to-glu substitution, which was confirmed at the protein level. The mutation occurred in the same codon as hemoglobin Olympia (141900.0210), which shows a val20-to-met amino acid substitution.


.0451 HEMOGLOBIN TYNE

HBB, PRO5SER
  
RCV000016806...

In a variant hemoglobin designated Hb Tyne, Langdown et al. (1994) observed a CCT-to-TCT change in codon 5 predicting substitution of serine for proline. The variant was first found in a 66-year-old diabetic male after an inappropriately low level of glycosylated hemoglobin was detected by enzyme immunoassay, and confirmatory ion exchange high performance liquid chromatography revealed the presence of an abnormal hemoglobin. Consequently, Langdown et al. (1994) identified the same mutation in an apparently unrelated diabetic male. Neither occurrence of the variant was associated with any abnormal hematologic findings.


.0452 HEMOGLOBIN MEDICINE LAKE

HBB, VAL98MET AND LEU32GLN
   RCV000016443...

Coleman et al. (1993, 1995) investigated the molecular basis of transfusion-dependent hemolytic anemia in a Caucasian female infant who rapidly developed the phenotype of beta-thalassemia major. Both the father and mother were normal hematologically. The DNA sequence of one HBB allele demonstrated 2 mutations, one for the moderately unstable Hb Koln (141900.0151) and another for a novel leu32-to-gln change resulting from a CTG to CAG transversion. The new hemoglobin was called Hb Medicine Lake. The hydrophilic gln32 has an uncharged polar side chain that may distort the B helix and provoke further molecular instability. Biosynthesis studies of this mutation showed a deficit of beta-globin synthesis with early loss of beta-globin chains. Coleman et al. (1995) pointed to 14 previously described hemoglobin variants with 2 mutations in the same polypeptide chain. Most of these rare disorders had probably arisen via homologous crossing over. Such a mechanism, however, could not account for the Hb Medicine Lake, since neither parent had a detectable abnormal hemoglobin gene. Therefore, it was presumed that this was a true double de novo mutation.


.0453 HEMOGLOBIN YAIZU

HBB, ASP79ASN
  
RCV000016341...

Harano et al. (1995) used the designation Hb Yaizu, after the city where the carrier lived, for a new beta-chain variant found in a Japanese female who was apparently healthy. Isoelectric focusing showed an abnormal hemoglobin band between the normal A2 and A bands. An asp79-to-asn amino acid substitution was demonstrated.


.0454 BETA-ZERO-THALASSEMIA

HBB, IVS2AS, G-A, -1
  
RCV000668023...

Curuk et al. (1995) described an American family of English-Scottish descent in which 6 members were found to be heterozygous for beta-thalassemia (613985). Sequencing of the HBB gene showed a G-to-A transition at the splice acceptor site of the second intron, changing the canonical AG to AA. Nucleotide 850 was involved; Curuk et al. (1995) commented that a G-to-C change in the same nucleotide had been found in a Yugoslavian family, whereas a frameshift due to deletion of nucleotide 850 was found in an Italian family. All 3 nucleotide changes lead to beta-zero thalassemia and are rare in the populations in which they were discovered.


.0455 HEMOGLOBIN HAKKARI

HBB, LEU31ARG
  
RCV000016810

Gurgey et al. (1995) observed a highly unstable hemoglobin variant in a 5-year-old Turkish girl with severe hemolytic anemia without Heinz body formation. A modest increase in liver and spleen size was present and level of Hb F was 33%. The variant could not be observed in red cells and was only detected through sequencing of the amplified beta-globin gene and also by hybridization with specific oligonucleotide probes. The variant was presumably a de novo mutation, since the parents were normal. Smears from bone marrow aspirates showed numerous inclusion bodies in erythroblasts and, as a result, erythroid hyperplasia. It was suggested that this hemoglobin variant was unstable and readily lost its heme group because one of the heme-binding sites had been lost and that, as a result, it precipitates in erythroblasts, thus interfering with the maturation process and causing severe anemia.


.0456 MOVED TO 141900.0430


.0457 HEMOGLOBIN PUTTELANGE

HBB, ALA140VAL
  
RCV000016811...

In 2 sibs with polycythemia in a French family, Wajcman et al. (1995) found a de novo ala140-to-val mutation. The hemoglobin displayed increased oxygen affinity, thus explaining the polycythemia. Both parents were phenotypically normal and study of polymorphic markers from several chromosomes were consistent with paternity. Since 2 brothers were affected, it was considered likely that the mutation had occurred in the germline of the father.


.0458 HEMOGLOBIN ARTA

HBB, PHE45CYS
  
RCV000016812

In a 22-year-old Caucasian female, known to be anemic from early childhood and showing scleral subicterus and slightly enlarged spleen on physical examination, Vassilopoulos et al. (1995) described a new unstable hemoglobin variant with reduced oxygen affinity. A phe45-to-cys amino acid substitution was found in beta-globin. The other chromosome 11 carried the gln39-to-ter (141900.0312) mutation that causes beta-zero-thalassemia. The new variant was named for the Greek city where the patient was born.


.0459 HEMOGLOBIN AURORA

HBB, ASN139TYR
  
RCV000016813

In a 73-year-old female of Dutch descent, Lafferty et al. (1995) found that a high oxygen affinity hemoglobin variant resulted from an AAT-to-TAT transversion of codon 139, resulting in an asn139-to-tyr amino acid substitution. See 141900.0092 for the asn139-to-asp mutation and 141900.0108 for the asn139-to-lys mutation involving the same codon.


.0460 HEMOGLOBIN NAKANO

HBB, LYS8MET
  
RCV000016814

During the assay of glycated hemoglobin by HPLC, Harano et al. (1995) identified a new hemoglobin named Hb Nakano for the district of Tokyo where healthy, 46-year-old Japanese woman lived and showed that it was due to a change of codon 8 from lysine to methionine. See 141900.0135 for the lys8-to-gln mutation, 141900.0191 for the lys8-to-glu mutation, and 141900.0237 for the lys8-to-thr mutation.


.0461 HEMOGLOBIN HINWIL

HBB, THR38ASN
  
RCV000016815

Frischknecht et al. (1996) found a new hemoglobin variant in the course of investigation of mild erythrocytosis. Mutation mapping of the beta-globin gene by PCR and denaturing gradient gel electrophoresis (DGGE) followed by sequence analysis revealed a C-to-A transversion at codon 38, predicting a thr38-to-asn substitution. In contrast to the other known mutation at codon 38, thr38-to-pro (known as Hb Hazebrouck; 141900.0101), Hb Hinwil was found to be stable and showed elevated oxygen affinity.


.0462 HEMOGLOBIN DEBROUSSE

HBB, LEU96PRO
  
RCV000016816

Lacan et al. (1996) described an unstable variant hemoglobin with high oxygen affinity responsible, in the steady state, for an apparently well-compensated chronic hemolytic anemia. The defect was shown to be a leu96-to-pro substitution in the HBB gene. The hemoglobin was named for the hospital in Lyon, France where the patient was observed. This electrophoretically neutral hemoglobin was found as a de novo case in a 6-year-old girl suffering from severe anemia with hemolysis and transient aplastic crisis following infection by parvovirus B19.


.0463 BETA-THALASSEMIA

HBB, 2-BP DEL, CC, CODONS 38-39
  
RCV000016817

In 3 members of an indigenous Belgian family with beta-thalassemia (613985), Heusterspreute et al. (1996) found a deletion of 2 nucleotides, CC, from codons 38 and 39. The mutation eliminates an AvaII restriction site and so can be routinely investigated by AvaII digestion of amplified DNA.


.0464 HEMOGLOBIN TSURUMAI

HBB, LYS82GLN
  
RCV000016818

In a 46-year-old Japanese male with plethora and erythrocytosis, Ohba et al. (1996) found a lys82gln amino acid substitution in the beta-globin chain. A son also had erythremia due to this hemoglobin variant.


.0465 HEMOGLOBIN J (EUROPA)

HBB, ALA62ASP
  
RCV000016819

In a 27-year-old man of Italian origin living in Belgium investigated because of mild polycythemia with microcytosis, Kiger et al. (1996) found that the hemoglobin had a negatively charged residue near the distal histidine and an ala62-to-asp substitution. The variant was called Hb J-Europa, presumably because it was found in the proband during a systematic physical examination performed before employment at the headquarters of the European Economic Community (EEC) in Luxembourg.


.0466 HB AUBENAS

HBB, GLU26GLY
  
RCV000016820

Lacan et al. (1996) found this mildly unstable variant in a French family without hematologic or clinical features. Although the substitution involves the same residue as in Hb E (141900.0071), the new sequence in this case did not create an additional out-of-frame splice site. The mutated chain was, therefore, normally synthesized.


.0467 HB CAMPERDOWN

HBB, ARG104SER
  
RCV000016789...

Miranda et al. (1996) described Hb Camperdown in a 24-year-old Brazilian woman of Italian origin. Although carriers do not show significant clinical alterations, Hb Camperdown is considered an unstable Hb.


.0468 BETA-THALASSEMIA, DOMINANT

HBB, 3-BP INS, CGG, CODON 30
  
RCV001078385...

Negri Arjona et al. (1996) described a Spanish family with a dominant type of beta-thalassemia (613985). Carriers were characterized by mild anemia, hyperchromia, microcytosis, elevated Hb A2 and Hb F levels, reticulocytosis, and splenomegaly. They found that the molecular basis was the introduction of a CGG triplet between codons 30 and 31 of the HBB gene; this was determined by sequencing of amplified DNA and confirmed by dot-blot analysis. The abnormal mRNA was stable and present in quantities similar to that of normal mRNA. The abnormal mRNA translated into a beta-chain that was 147 amino acid residues long and carried an extra arginine residue between residues 30 and 31. The abnormal beta chain may be unstable and does not bind to the alpha-chain. It probably is continuously digested by proteolytic enzymes in red cell precursors in the bone marrow. The abnormal chain probably binds haem that is excreted after proteolysis causing a darkening of urine, which was a clinical characteristic of the disorder. The insertion occurred at the 3-prime end of IVS1 and the 5-prime end of exon 2. The insertion may have an addition of CGG between codons 30 and 31 or an insertion of GGC between IVS1 129/130.


.0469 HEMOGLOBIN COSTA RICA

HBB, HIS77ARG
  
RCV000016822

Rodriguez Romero et al. (1996) discovered an abnormal beta-chain hemoglobin Hb Costa Rica, or beta-his77arg, in a healthy young Costa Rican female. This stable hemoglobin, termed Hb Costa Rica, was present in only 6 to 8% of hemoglobin and was not observed in any relative (the father was not available for study). The expected CAC-to-CGC mutation could not be detected in genomic DNA. Smetanina et al. (1996) presented convincing evidence that the CAG-to-CGC mutation at codon 77 of the HBB gene had occurred as a somatic mutation during embryonic development and resulted in mosaicism with only 6 to 8% of the abnormal Hb Costa Rica in circulating red cells. Bradley et al. (1980) had described an instance of gonadal mosaicism accounting for an unusual pedigree pattern in a family with Hb Koln (141900.0151). Smetanina et al. (1996) incorrectly stated that theirs was the first example of mosaicism in a hematopoietic system.


.0470 BETA-THALASSEMIA, ASHKENAZI JEWISH TYPE

HBB, 1-BP INS, CODON 20/21, FS
  
RCV000666440...

Beta-thalassemia (613985) alleles are uncommon among Ashkenazi Jews as compared with Sephardic Jews and other populations. Oppenheim et al. (1993) described a rare allele, a single-base insertion resulting in a frameshift at codon 20/21, in an Ashkenazi Jewish proband with beta-thalassemia (613985) living in Israel. Martino et al. (1997) independently discovered this allele (called fs20/21 by them) in a Montreal Ashkenazi pedigree and investigated the possibility of genealogic connections between the 2 families. They showed by analysis of the mutation and the associated marker haplotype that the Israeli and Montreal probands appeared to be identical by descent and certainly had identity by state at the HBB locus. Genealogic reconstruction suggested that the 2 families had a shared origin in time and space.


.0471 HB NIIGATA

HBB, VAL1LEU
  
RCV000016824

Ohba et al. (1997) reported the fifth variant with retention of the initiator methionine and partial acetylation. The proband, a 37-year-old Japanese male, was subjected to detailed studies because of an unexpectedly high HbA1c value on cation exchange high performance liquid chromatography. The findings of their subsequent studies, as well as previous reports, suggested that retention of the initiator methionine and acetylation have no physiologic or pathologic significance, at least on human hemoglobin. The authors found that the variant hemoglobins were not unstable in in vitro tests. Ohba et al. (1997) stated that they must be almost as stable as normal HbA in vivo because they comprise over 40% of total Hb in the peripheral blood. The 4 previously reported Hb variants with retention of initiator methionine were Hb Thionville (141800.0168), Hb Marseille (141900.0171), Hb Doha (141900.0069), and Hb South Florida (141900.0266).

This variant was numbered based on the first amino acid of the mature protein. In the gene-based system of counting, this variant is VAL2LEU.


.0472 BETA-ZERO-THALASSEMIA

HBB, 5-BP DEL AND 1-BP INS
  
RCV000016826...

Waye et al. (1997) described a beta-thalassemia (613985) trait in a Caucasian woman of British descent living in Ontario, Canada. The 48-year-old woman presented with typical high Hb A2 beta-thalassemia trait. All known family members were of British ancestry. Her father had normal hematologic indices and her mother was deceased. There was no family history of anemia. Direct nucleotide sequencing demonstrated a complex frameshift mutation due to deletion of 5 nucleotides (AGTGA) and insertion of 1 nucleotide (T) at codons 72/73 of the HBB gene. This introduced a premature stop codon (TGA) at codon 88, resulting in beta-zero-thalassemia.


.0473 HB GAMBARA

HBB, LYS82GLU
  
RCV000016827

In a Lombardy family (from Gambara, near Brescia in Northern Italy), Ivaldi et al. (1997) described a 45-year-old man and his 2 daughters who carried an abnormal hemoglobin resulting in modest erythrocytosis and mild, compensated hemolysis with slight splenomegaly. The abnormal hemoglobin represented about 52% of the total hemoglobin, and was shown to be stable by the isopropanol test. Sequencing demonstrated a change in the HBB gene of codon 82 from AAG (lys) to GAG (glu) in heterozygous state.


.0474 BETA-ZERO-THALASSEMIA

HBB, IVS1AS, A-G, -2
  
RCV000016828...

Waye et al. (1998) studied the hemoglobin of a 37-year-old woman who presented during pregnancy with the beta-thalassemia (613985) trait. The father and mother were Sephardic Jews whose families had lived for many generations in Tangiers and Gibraltar, respectively. The HBB gene was found to have a single basepair substitution at codon 30: AGG (arg) to GGG (gly). The mutation changed the sequence immediately upstream of the 5-prime splice junction of the first intron: A-to-G at position -2 of IVS1. The authors stated that although mutations had been found at positions -1 and -3 of IVS1, no mutation had been described at the -2 position. The authors thought it unlikely that an arg30-to-gly substitution was responsible for the abnormality and favored the possibility that the mutation impaired the normal splicing of the beta-globin pre-mRNA.

Li et al. (1998) identified the same mutation in a Chinese man whose wife carried the 4-bp deletion at codons 41/42 (141900.0326) that is a common beta-thal mutation in Japanese. Their son had died of severe anemia at age 4 and the authors speculated that he had beta-0-thalassemia due to compound heterozygosity for these mutations.


.0475 BETA-ZERO-THALASSEMIA

HBB, 1-BP INS, T, CODON 26
  
RCV000016829...

Hattori et al. (1998) identified a new beta-thalassemia (613985) allele in a 31-year-old Japanese man who was found to have microcytosis and erythrocytosis during a health check-up. His red blood cell count was 6.53 x 10(12) per liter. The HBB gene in 1 allele was found to have an insertion of T at codon 26: GAG-to-GTAG. The frameshift mutation was expected to result in beta-zero-thalassemia because the translation of the abnormal mRNA produced a peptide with an abnormal amino acid sequence from codon 26 to 42 where it terminates. Such a truncated peptide of 42 residues would be immediately eliminated by proteolysis. Codon 26 is involved in the consensus sequence for cryptic splicing at codon 25. The insertion of T at codon 26 breaks the consensus sequence and is unlikely to affect the alternative splicing. Results of SSCP analysis indicated that the patient was heterozygous for the frameshift.


.0476 HEMOGLOBIN SILVER SPRINGS

HBB, GLN131HIS
  
RCV000016830

Hoyer et al. (1998) described a new hemoglobin variant called Hb Silver Springs which resulted from a CAG (gln)-to-CAC (his) change at codon 131 of the beta chain. It was detected only by cationic exchange high performance liquid chromatography. This was the fifth reported substitution at codon 131. The variant did not appear to have any clinical or hematologic manifestations. It was found in 6 African Americans from 4 presumably unrelated families.


.0477 HEMOGLOBIN BURTON-UPON-TRENT

HEMOGLOBIN OLD DOMINION
HBB, HIS143TYR
  
RCV000016831...

In investigating the nature of the unique hemoglobin variant that caused a spurious increase in glycated hemoglobin, Hb A(1c), Elder et al. (1998) found a CAC-to-TAC mutation in the HBB gene that resulted in a his143-to-tyr substitution in the beta-globin peptide. This amino acid substitution affected an important 2,3-diphosphoglycerate binding site and slightly increased the oxygen affinity of the hemoglobin variant. Despite the slight increase in oxygen affinity, the mutation was without hematologic effect, and its only clinical significance was that it coeluted with Hb A(1c) on ion-exchange chromatography and compromised the use of this analyte to monitor the treatment of diabetes mellitus. The variant was encountered in 4 unrelated persons of Irish or Scottish-Irish ancestry.

Gilbert et al. (2000) reported 2 unrelated cases of Hb Old Dominion/Burton-upon-Trent.

Plaseska-Karanfilska et al. (2000) found the same mutant hemoglobin in a 72-year-old Korean woman with type II diabetes (125853).


.0478 HEMOGLOBIN RIO CLARO

HBB, VAL34MET
  
RCV000016833...

By globin chain electrophoresis, Grignoli et al. (1999) detected a novel silent hemoglobin variant in a 4-year-old Caucasian Brazilian boy of Italian descent, and in his mother. Sequencing of the HBB gene revealed a G-to-A transition at the first position of codon 34, resulting in a val-to-met substitution. In the boy, this variant was found to be associated with Hb Hasharon (141850.0012) and alpha-thalassemia-2 (rightward deletion).


.0479 HEMOGLOBIN NIJKERK

HBB, 4-BP DEL/1-BP INS, CODONS 138/139, GCTA/T
  
RCV000016834...

Van den Berg et al. (1999) identified a novel Hb B variant, termed Hb Nijkerk, in a Caucasian Dutch girl who was slightly icteric at birth and developed hemolytic anemia and hepatosplenomegaly at about 5 months of age. Red cell transfusions were necessary every 3 to 4 weeks. Erythromorphology was markedly abnormal, with large numbers of red cells with inclusion bodies. Splenectomy was performed at the age of 18 months, after which the need for transfusions decreased and they were finally discontinued. Although still anemic, the child's growth was otherwise normal. Repeated hemoglobin electrophoresis on cellulose acetate revealed no abnormalities. At the age of 17 years, a minor abnormal band, migrating slightly faster than Hb A2, was detected on starch gel electrophoresis. Sequencing of the HBB gene revealed heterozygosity for a 4-bp deletion (GCTA) in combination with a 1-bp insertion (T) at codons 138/139. This event eliminated 2 amino acids (ala and asn) and introduced a new residue (tyr) into the protein. The parents did not carry the mutation and paternity analysis showed no discrepancies, indicating that Hb Nijkerk should be considered as a de novo event.


.0480 HEMOGLOBIN CHILE

HBB, LEU28MET
  
RCV000016835

Hojas-Bernal et al. (1999) identified a novel Hb B gene variant, termed Hb Chile, in a 57-year-old Native American living in Chile who was known to be chronically cyanotic. He was hospitalized for elective surgery of left pyeloureteral stenosis. Prior to surgery, he was given sulfonamides. Surgery was terminated when the dark color of his blood was noted. Arterial oxygen saturation was 80%. His blood contained 18% methemoglobin. Repeated intravenous methylene blue was given for the methemoglobinemia but to no avail. Sulfhemoglobin was not increased. Subsequently, an acute episode of hemolytic anemia occurred. Red cell glucose-6-phosphate dehydrogenase and methemoglobin reductase were normal. The patient's father and 1 of his 2 children also showed cyanosis. Tryptic digestion of the beta-globin chain and subsequent chromatography revealed an abnormal beta-T-3 peptide; sequencing revealed a leu-to-met substitution at position 28, predicted to be caused by a CTG-to-ATG transversion in the HBB gene. Hojas-Bernal et al. (1999) concluded that Hb Chile is an unstable hemoglobin that forms methemoglobin in vivo spontaneously at an accelerated rate and predisposes to drug-induced hemolytic anemia.


.0481 HEMOGLOBIN TENDE

HBB, PRO124LEU
  
RCV000016836...

By chromatographic measurement of glycated Hb in a 90-year-old woman of French origin, Wajcman et al. (1998) identified a novel hemoglobin variant, termed Hb Tende, that showed a moderate increase in oxygen affinity. Sequencing of the HBB gene revealed a CCA-to-CTA transition, resulting in a pro124-to-leu substitution. Three hemoglobin variants at amino acid 124 had been previously described: Hb Tunis (pro124 to ser; 141900.0288) is asymptomatic; Hb Khartoum (pro124 to arg; 141900.0148) is mildly unstable; and Hb Ty Gard (pro124 to gln; 141900.0289) is responsible for increased oxygen affinity leading to erythrocytosis. Wajcman et al. (1998) suggested that the absence of erythrocytosis in the Hb Tende carrier whom they studied was likely due to the relatively low proportion of abnormal Hb (34%), possibly explained by the mild instability revealed by the isopropanol test, and to the normal cooperativity of the variant.


.0482 HEMOGLOBIN LA ROCHE-SUR-YON

HBB, LEU81HIS
  
RCV000016837

Wajcman et al. (1992) identified Hb La Roche-sur-Yon, an unstable hemoglobin variant resulting from a leu81-to-his substitution in the HBB gene. The variant displayed a moderately increased oxygen affinity. in addition to the substitution at beta-81, about half the abnormal hemoglobin carried a deamidation of the neighboring asparagine residue at beta-80. The authors concluded that the deamidation depends not only on the flexibility of the polypeptide region but also on the presence of a neighboring histidine residue to catalyze the reaction. See also Hb Redondo (141900.0404).


.0483 HEMOGLOBIN IRAQ-HALABJA

HBB, ALA10VAL
  
RCV000016838

In a family originating from Iraq, Deutsch et al. (1999) identified a novel beta-chain silent variant, a change of codon 10 from GCC to GTC (ala10 to val), in association with thalassemia. The variant, which they designated Hb Iraq-Halabja, gave a normal oxygenation curve, a normal heterotopic action of 2,3-DPG, and normal heat stability and isopropanol precipitation tests. The variant showed a clear difference in migration properties compared to normal beta chain only when run on PAGE urea Triton. The codon involved in Hb Iraq-Halabja is the same as that mutant in Hb Ankara (141900.0009), in which the substitution is ala10 to asp.


.0484 HEMOGLOBIN LUCKNOW

HBB, LYS8ARG
  
RCV000016839

Agarwal et al. (1999) found an A-to-G transition in exon 1 of the HBB gene at codon 8 which resulted in a lys8-to-arg amino acid substitution. This change was associated with a splice mutation and was speculated to produce a thalassemia intermedia phenotype in the subject.


.0485 HEMOGLOBIN SAGAMI

HBB, ASN139THR
  
RCV000016840

Miyazaki et al. (1999) described compound heterozygosity for a beta(+)-thalassemia mutation and a new beta variant with low oxygen affinity, Hb Sagami (asn139 to thr).


.0486 HEMOGLOBIN HARROW

HBB, PHE118CYS
  
RCV000016841

Henthorn et al. (1999) reported a new beta-globin variant, phe118 to cys, found in a newborn male of Indian Gujerati origin, living in the Harrow area of London, England. This variant was observed during a systematic program of neonatal screening. The mother also carried the abnormal hemoglobin.


.0487 HEMOGLOBIN BRIE COMTE ROBERT

HBB, PRO36ALA
  
RCV000016842

Wajcman et al. (1999) described a beta-globin variant in a 36-year-old French Caucasian male who presented with polycythemia. The variant was named Hb Brie Comte Robert for the place where the carrier resided. It was shown to have high oxygen affinity.


.0488 HEMOGLOBIN BARBIZON

HBB, LYS144MET
  
RCV000016843

In several members of a French family, Kister et al. (1999) identified a lys144-to-met mutation in the HBB gene. The mutation is a clinically silent variant in which the structural modification disturbs the oxygen-linked chloride binding.


.0489 HEMOGLOBIN BOLOGNA-ST. ORSOLA

HBB, HIS146TYR
  
RCV000016844

In 3 members of a family from Bologna, Italy, Ivaldi et al. (1999) demonstrated that erythrocytosis was the result of a variant beta-globin chain, a CAC-to-TAC mutation in codon 146 leading to a his146-to-tyr amino acid substitution. Ivaldi et al. (1999) pointed out that this was the sixth substitution that had been identified in the C-terminal residue of the beta-globin chain, the others being his146-to-asp (141900.0110), his146-to-pro (141900.0305), his146-to-leu (141900.0056), his146-to-arg (141900.0051), and his146-to-gln (141900.0409).

Gilbert et al. (2000) described a second case of Hb Bologna-St. Orsola in a family of Anglo-Celtic origin.


.0490 HEMOGLOBIN VILA REAL

HBB, PRO36HIS
  
RCV000016845...

In a 15-year-old Portuguese girl with erythrocytosis, Bento et al. (2000) found a new high oxygen affinity variant called Hb Vila Real and characterized by a pro36-to-his (P36H) missense mutation of the HBB gene. The patient's mother had undergone regular phlebotomies over the previous 20 years for polycythemia, with an obstetric history of 2 miscarriages, a stillborn baby, and 2 normal children by elective Cesarean section. A transversion converted codon 36 from CCT to CAT. The variant was named after the city in Portugal where the carrier was born.

Salzano et al. (2002) reported the same rare high oxygen affinity hemoglobin variant in a 22-year-old male patient from Naples, Italy, affected by erythrocytosis. The DNA mutation was identified as a change in codon 36 of the HBB gene from CCT to CAT. The father carried the same hemoglobin variant in heterozygous state.


.0491 HEMOGLOBIN SAALE

HBB, THR84ALA
  
RCV000016846...

In a 3-year-old anemic German girl, Bisse et al. (2000) detected an abnormal hemoglobin by cation-exchange high performance liquid chromatography. Further studies characterized the variant as a thr84-to-ala replacement in the HBB gene, which the authors named Hb Saale for the river crossing the city in which the proband lived. Hb Saale could be not be separated by electrophoresis or isoelectric focusing. It was found to be slightly unstable, exhibiting a moderate tendency to autooxidize. Functional properties and the heterotropic interactions were similar to those of hemoglobin A.


.0492 HEMOGLOBIN BUSHEY

HBB, PHE122LEU
  
RCV000016847...

Wajcman et al. (2000) found a hemoglobin variant, designated Hb Bushey, in a Chinese baby and his father. The variant was found to be caused by a point mutation leading to a phe122-to-leu substitution in the HBB gene. The same amino acid substitution was found in Hb Casablanca (141900.0493), in combination with another abnormality in the HBB gene, i.e., a lys65-to-met amino acid substitution (Hb J (Antakya); 141900.0121).


.0493 HEMOGLOBIN CASABLANCA

HBB, LYS65MET AND PHE122LEU
  
RCV000016398...

Wajcman et al. (2000) found a hemoglobin variant in a family in Morocco and designated it Hb Casablanca. It was found to be another example of a hemoglobin variant with 2 abnormalities in the same chain: the first was identical to that of Hb Bushey (phe122 to leu; 141900.0492) and the second to that of Hb J (Antakya) (lys65 to met; 141900.0121). The stability and oxygen-binding properties of Hb Bushey and Hb Casablanca were identical to those of Hb A.


.0494 HEMOGLOBIN TSUKUMI

HBB, HIS117TYR
  
RCV000016849

Oribe et al. (2000) found a new hemoglobin variant in a Japanese male: a change at codon 117 of the HBB gene from CAC (his) to TAC (tyr). The authors designated this variant Hb Tsukumi after the patient's place of residence. Two other hemoglobin variants have a change in his117: a change to arg in the case of Hb P (Galveston) (141900.0213), and a change to pro in the case of Hb Saitama (141900.0250).

North et al. (2001) found Hb Tsukumi in a Moroccan woman.


.0495 HEMOGLOBIN ERNZ

HBB, THR123ASN
  
RCV000016851...

Analysis of globin chains by reversed phase high performance liquid chromatography, used as an additional tool for characterizing hemoglobin variants, led to the discovery of a new class of variants that display only differences in hydrophobicity. Groff et al. (2000) described 2 such variants: Hb Ernz and Hb Renert (141900.0496). Hb Ernz, a thr123-to-asn substitution, was found in a man of Italian origin who was polycythemic and in 2 of his 3 daughters who were hematologically normal. See 141900.0294 for a thr123-to-ile substitution.


.0496 HEMOGLOBIN RENERT

HBB, VAL133ALA
  
RCV000016852

Groff et al. (2000) identified Hb Renert, a val133-to-ala substitution in the HBB gene, in a man from Cape Verde who also carried Hb S (141900.0243) and presented with chronic hemolysis.

Wilson et al. (2001) described a second case of Hb Renert. They commented that this was only the second hemoglobin variant involving beta-133, the other being Hb Extremadura (V1133L; 141900.0074).


.0497 HEMOGLOBIN WATFORD

HBB, VAL1GLY
  
RCV000016854

Four hemoglobin variants had previously been described that involve the first codon of the HBB gene: Hb Doha (141900.0069), Hb South Florida (141900.0266), Hb Niigata (141900.0471), and Hb Raleigh (141900.0233). Although none of these variants cause any significant clinical problems, mutations of the first codon are of interest because of their potential interference with cotranslational modification at this site during beta-globin synthesis. In eukaryotes, the translation of all peptide mRNAs starts at an AUG codon, producing methionine at the beginning of the nascent peptide chain. In most proteins, including alpha-, beta-, and gamma-globin, this methionine is cotranslationally cleaved when the chain is 20 to 30 amino acids long. This results in the first amino acid being valine in alpha-, beta-, and delta-globin, and glycine in gamma-globin. When the peptide chain is 40 to 50 amino acids long, further modification occurs with acetylation at the NH2-terminal residue. The extent of the acetylation depends on the identity of the N-terminal amino acid; valine is strongly inhibitory to this process, leading to little acetylation of alpha- and beta-globin. However, the N-terminal glycine of gamma-globin is less inhibitory, resulting in about 15% acetylation. Fisher et al. (2000) identified a new Hb variant, Hb Watford, in which a GTG-to-GGG substitution caused a change of the first amino acid of the beta-globin chain from methionine to glycine, mimicking the gamma-globin chain. The proband was a 48-year-old female of Jewish extraction who was evaluated for chronic mild anemia. Another mutation was found in cis with the val1-to-gly mutation: Cap+36G-A.


.0498 HEMOGLOBIN YAOUNDE

HBB, VAL134ALA
  
RCV000016855...

Yapo et al. (2001) described a val134-to-ala missense mutation of the HBB gene in a 45-year-old man originating from Cameroon, a migrant worker in France. He was a compound heterozygote for this mutation, designated Hb Yaounde, and for Hb Kenitra (141900.0147). Hb Kenitra had previously been described only in persons of Moroccan origin. Hb Yaounde appeared to be neutral; Hb Kenitra is associated with expression at a level slightly higher than that of Hb A.

Faustino et al. (2004) described Hb Yaounde in a 3-generation Portuguese family. The proband had compound heterozygosity for this hemoglobin variant and for hemoglobin C (glu6 to lys; 141900.0038). Hb Yaounde was associated with the Mediterranean haplotype II, supporting the hypothesis of a genetic origin independent of the African origin.


.0499 HEMOGLOBIN SITIA

HBB, ALA128VAL
  
RCV000016850...

Papassotiriou et al. (2001) identified hemoglobin Sitia, an ala128-to-val missense mutation in the HBB gene, in a Greek female with slightly reduced red blood cell indices.


.0500 HEMOGLOBIN MONT SAINT-AIGNAN

HBB, ALA128PRO
  
RCV000016856

In a 33-year-old French Caucasian woman displaying a well-tolerated chronic anemia, Wajcman et al. (2001) found Hb Mont Saint-Aignan, a mildly unstable variant associated with hemolytic anemia, marked microcytosis, and increased alpha/beta biosynthetic ratio. The molecular defect was an ala128-to-pro missense mutation of the HBB gene.


.0501 HEMOGLOBIN 'T LANGE LAND

HBB, GLY136ARG
  
RCV000016857

In a Dutch patient of Chinese origin, Harteveld et al. (2001) identified a new hemoglobin variant, Hb 't Lange Land, caused by a GGT-to-CGT transversion at codon 136 in exon 3 of the HBB gene, predicted to result in a gly136-to-arg (G136R) substitution. The authors stated that 3 mutations inducing a single amino acid substitution at codon 136 were known: Hb Hope (gly136 to asp; 141900.0112), and 2 others based on personal communication from H. Wajcman, Hb Petit Bourg (gly136 to ala) and Hb Perpignan (gly136 to ser).


.0502 HEMOGLOBIN D (AGRI)

HBB, SER9TYR AND GLU121GLN
  
RCV000016317...

In an asymptomatic Indian male belonging to the Agri caste group and originating from Mumbai in Maharashtra State, India, Colah et al. (2001) found a new hemoglobin variant, Hb D (Agri), with 2 amino acid substitutions in the same beta chain: glu121 to gln (141900.0065) and ser9 to tyr.


.0503 HEMOGLOBIN ANTALYA

HBB, 9-BP DEL/INS
  
RCV001078387...

Keser et al. (2001) identified a 9-bp (TCTGACTCT) deletion/insertion at codons 3-5 of the HBB gene in a 26-year-old woman with beta-thalassemia trait. The change was found to be the result of a deletion of cytosine (-C) at codon 5 (1 of the nucleotides in the thirteenth or fourteenth position of exon 1), and an insertion of thymine (+T) in front of codon 3 at the tenth nucleotide in exon 1 of the HBB gene. As a result of these mutations, the amino acids at codons 3-5 were changed from leu-thr-pro to ser-asp-ser. This partial frameshift mutation led to a very unstable beta-globin chain.


.0504 HEMOGLOBIN LIMASSOL

HBB, LYS8ASN
  
RCV000016860

Kyrri et al. (2001) found a nonpathologic Hb variant in a Greek Cypriot male originating from Limassol, a town on the south coast of Cyprus. A G-to-C substitution in codon 8 (AAG to AAC) led to a lys8-to-asn (K8N) amino acid substitution. The 4 previously described amino acid substitutions at residue 8 of the beta-globin chain (lys8 to thr, 141900.0237; lys8 to gln, 141900.0135; lys8 to glu, 141900.0191; and lys8 to met, 141900.0460), and the 2 hemoglobin variants with amino acid substitutions at the equivalent residue of the alpha-globin chain (lys7 to asn, 141800.0187 and lys7 to glu, 141800.0192) are nonpathologic as well.


.0505 THALASSEMIA INTERMEDIA

HBB, DEL, SOMATIC
  
RCV000016861

Badens et al. (2002) described a 'new' mechanism leading to thalassemia intermedia (613985), a moderate form of thalassemia: a somatic deletion of the HBB gene in the hemopoietic lineage of a heterozygous beta-thalassemic patient. The deletion occurred on the chromosome 11 inherited from the mother, who had no abnormality of the HBB gene. The father had a beta-thalassemic trait due to the Mediterranean HBB nonsense mutation (141900.0312). The deletion gave rise to a mosaic of cells with either 1 or no functional beta-globin gene and it extended to a region of frequent loss of heterozygosity called LOH11A, which is located close to the HBB locus. Thus, loss of heterozygosity can be a cause of nonmalignant genetic disease.


.0506 HEMOGLOBIN CANTERBURY

HBB, CYS112PHE
  
RCV000016862

Brennan et al. (2002) found hemoglobin Canterbury by chance when a supposedly normal lysate was used as a control for an isopropanol stability test. The sample came from a 55-year-old man with Cowden disease (601728). The isopropanol stability test showed a precipitate, suggesting a slightly unstable hemoglobin.


.0507 HEMOGLOBIN O (TIBESTI)

HBB, GLU121LYS, VAL11ILE
  
RCV000016370...

Prehu et al. (2002) described a heterozygous hemoglobin variant that combined the change of Hb O-Arab (141900.0202) and Hb Hamilton (141900.0099) on the same HBB allele. The other allele carried the Hb S mutation (141900.0243). The patient was a child of Chad-Sudanese descent, suffering from a sickle cell syndrome. Compared to the classic description of the Hb S/Hb O-Arab association, the additional Hb Hamilton mutation did not seem to modify the clinical presentation.


.0508 HEMOGLOBIN MOLFETTA

HBB, VAL126LEU
  
RCV000016864

Qualtieri et al. (2002) identified a new neutral hemoglobin variant in a pregnant Italian woman that resulted from a GTG-to-CTG replacement at codon 126 of the HBB gene, corresponding to a val-to-leu amino acid change. Thermal and isopropanol stability tests were normal and there were no abnormal clinical features.


.0509 BETA-THALASSEMIA, DOMINANT

HBB, 1-BP DEL
   RCV001731306

Waye et al. (2002) described a case of dominant beta-thalassemia (613985) in a 38-year-old Canadian male of northern European extraction. He was anemic at birth and required periodic blood transfusions until about 2 years of age. Subsequently, he was under close medical supervision for his anemia and thrombocytosis, but did not require further transfusions. He had been asymptomatic throughout childhood. At age 20 years, he was found to have splenomegaly, and splenectomy was performed at age 23 because of mild symptoms and to prevent splenic rupture during karate competitions. After surgery he received Pneumovax, a prophylaxis against pneumococcal infections. He remained on folic acid supplementation, which had been started in childhood. The family history was negative for hematologic disorders. He was shown to have the normal complement of 4 alpha-globin genes. He was heterozygous for a single-nucleotide deletion in the HBB gene converting codon 113 from GTG to TG. This frameshift mutation was predicted to give rise to an extended beta chain of 156 amino acid residues. It was considered to be a de novo mutation. The mutation in this case most closely resembled that of Hb Geneva (141900.0335), an unstable beta-chain variant due to a complex rearrangement at codon 114. Both mutations give rise to extended beta chain variants of 156 amino acids differing only at residues 113 and 114 (cys-val for the codon 113 mutation and val-gly for the codon 114 mutation). In both instances, it was not possible to detect even a trace of the predicted Hb variant in carriers of the mutation.

Waye et al. (2002) stated that more than 30 dominant beta-thalassemia alleles had been reported.


.0510 HEMOGLOBIN KODAIRA II

HBB, HIS146GLN
  
RCV000016868

So et al. (2002) described a 35-year-old woman in whom a beta-chain variant was found on assay for Hb A(1c) performed because of impaired glucose tolerance during pregnancy. The raised hemoglobin level was suggestive of a hemoglobin variant with high oxygen affinity. The patient was heterozygous for a CAC-to-CAG transversion at codon 146, corresponding to a substitution of histidine by glutamine in the beta-globin chain. The same amino acid substitution at codon 146 occurs in the high oxygen affinity variant Hb Kodaira (141900.0409); however, Hb Kodaira resulted from a point mutation of CAC-to-CAA at codon 146. Not unexpectedly, the phenotypic manifestation of the 2 mutations was identical. This second form of his146 to gln (H146Q) was referred to as hemoglobin Kodaira II.

Ngiwsara et al. (2003) described a case of Hb Kodaira II in Thailand.


.0511 HEMOGLOBIN ILMENAU

HBB, PHE41CYS
  
RCV000016865

Prehu et al. (2002) described a novel unstable hemoglobin variant with low oxygen affinity and called it Hb Ilmenau for the city where the patient lived. The variant hemoglobin had a phe41-to-cys (F41C) substitution due to a TTC-to-TGC transversion in codon 41. The patient was a 29-year-old man who had suffered from anemia since childhood. When he was 4 years old, a nonspherocytic anemia was diagnosed with hepatosplenomegaly and cyanosis for which no cardiac origin could be found. He was splenectomized at the age of 8 years, without any significant clinical or biologic improvement.


.0512 HEMOGLOBIN AUBAGNE

HBB, GLY64ALA
  
RCV000016866...

In a 32-year-old woman from Provence, southeast France, Lacan et al. (2002) found a novel unstable beta-chain variant with a GGC-GCC transversion resulting in a gly64-to-ala (G64A) substitution. The presence of Heinz bodies and reduced percentage (23 to 35%) of the abnormal hemoglobin fraction suggested a moderate instability in the hemoglobin, which the authors designated Hb Aubagne.


.0513 HEMOGLOBIN COLIMA

HBB, SER49CYS
  
RCV000016869...

Cobian et al. (2002) found Hb Colima, a ser49-to-cys change (S49C) of the beta-globin chain, in a 52-year-old Mestizo female who was born in Colima, Mexico. This was the second mutation at beta-49, the first being Hb Las Palmas (ser49 to phe), a slightly unstable variant (141900.0155).


.0514 HEMOGLOBIN POCOS DE CALDAS

HBB, LYS61GLN
  
RCV000016870

During a screening for hemoglobinopathies in blood donors in Brazil, Kimura et al. (2002) identified a beta-globin variant in a 30-year-old Caucasian woman of mixed Native Indian and Italian origin. The base substitution in codon 61 of the HBB gene from AAG to CAG caused a lys-to-gln (K61Q) change. This was the fourth description of a missense mutation at lys61 of the HBB gene: see Hb N-Seattle (K61E; 141900.0190), found in a black American blood donor; Hb Hikari (K61N; 141900.0106), found in a Japanese family; and Hb Bologna (K61M; 141900.0024), found in a northern Italian family. The missense mutations found at this position (external contacts of the Hb molecule) did not cause clinical manifestations; all the carriers described had been asymptomatic.


.0515 HEMOGLOBIN TRENTO

HBB, 1-BP DEL, 144A
  
RCV000016871

In a 31-year-old woman from Trento in northeastern Italy, Ivaldi et al. (2003) found anomalous hemoglobin: an elongated C-terminal variant due to deletion of an A in codon 144. The deletion led to the replacement of lysine by serine at residue 144, the disappearance of the stop codon at position 147, and the presence of 12 additional residues, identical to those observed in hemoglobins Saverne (141900.0255), Tak (141900.0279), and Cranston (141900.0057), which result from a similar mechanism. Hb Trento, amounting to 29% of the total hemoglobin, was unstable and, like the other variants of this group, had an increased oxygen affinity. It led to a mild compensated hemolytic anemia with red cell inclusion bodies.


.0516 HEMOGLOBIN SANTANDER

HBB, VAL34ASP
  
RCV000016872

In a 22-year-old Spanish male presenting with jaundice and suffering from hemolytic crises during infections, Villegas et al. (2003) identified an unstable Hb variant in which the valine residue at position 34 of the beta-globin chain was replaced by aspartic acid (val34 to asp; V34D).


.0517 HEMOGLOBIN BUZEN

HBB, ALA138THR
  
RCV000016873

During glycohemoglobin determination by HPLC in a 76-year-old Japanese woman, Miyazaki et al. (2003) identified a homozygous change of codon 138 of the HBB gene from GCT (ala) to ACT (thr) (A138T). No information on the clinical state of the patient was provided. In Hb Brockton (141900.0032), ala138 is changed to pro. Heinz body hemolytic anemia has been observed with that mutation.


.0518 HEMOGLOBIN SANTA CLARA

HBB, HIS97ASN
  
RCV000016874

In a 6-month-old infant and in her mother of Mexican ancestry who lived in San Jose, California, Hoyer et al. (2003) identified a hemoglobin variant with abnormal oxygen affinity, designated Hb Santa Clara. A change of codon 97 of the HBB gene from CAC to AAC resulted in a his97-to-asn (H97N) change. Both the infant and her mother exhibited mild erythrocytosis.


.0519 HEMOGLOBIN SPARTA

HBB, PHE103VAL
  
RCV000016875

In a 29-year-old Caucasian woman who lived near Sparta, Michigan, Hoyer et al. (2003) identified a hemoglobin variant with high oxygen affinity, designated Hb Sparta. A smoker of 1 pack per day for 15 years, she was found to have mild erythrocytosis. A change of codon 103 of the HBB gene from TTC to GTC resulted in a phe103-to-val (F103V) change. Phe103 is replaced by leu in Hb Heathrow (141900.0102), and by ile in Hb Saint Nazaire (141900.0436); both variants are associated with erythrocytosis.


.0520 BETA-THALASSEMIA, DOMINANT INCLUSION BODY TYPE

HBB, INS/DEL, EX3
  
RCV001078374...

Weatherall et al. (1973) described an Irish family with an unusual form of beta-thalassemia (613985) that was characterized by anemia, splenomegaly, and gross abnormalities of the erythrocytes and their precursors; the disorder was transmitted through several generations in an autosomal dominant fashion. Initially the disorder was labeled dyserythropoietic anemia, congenital, Irish or Weatherall type (603902). Thein et al. (1990) restudied the Irish family and 3 similarly affected kindreds, all of Anglo-Saxon origin, and pointed to similar cases reported by others and to the fact that the designation inclusion body beta-thalassemia had been proposed (Stamatoyannopoulos et al., 1974). All affected members of the original Irish family had a moderate anemia with splenomegaly, increased levels of Hb A2 and Hb F, and increased alpha/beta chain synthesis ratios. Two family members had undergone splenectomy. By the time of the report of Thein et al. (1990), 1 family member had died, showing at autopsy extensive extramedullary hemopoiesis and iron overload in parenchymal tissues in a pattern typical of excessive iron absorption rather than transfusion. The family had a complex rearrangement in the third exon of the HBB gene that involved 2 deletions, 1 of 4 bp in codons 128 and 129 and the other of 11 bp in codons 132-135. The deletions were interrupted by an insertion of 5 bp, CCACA, followed by the normal sequence of 8 nucleotides. The modification resulted in a frameshift reading through to codon 153, predicting the synthesis of a variant beta-globin 7 residues longer than normal. Thein et al. (1990) suggested that the phenotypic difference between this condition and the more common recessive forms of beta-thalassemia lies mainly in the length and stability of the abnormal translation products that are synthesized and, in particular, whether they are capable of binding heme and producing aggregations that are relatively resistant to proteolytic degradation.


.0521 HEMOGLOBIN S (CAMEROON)

HBB, GLU6VAL AND GLU90LYS
  
RCV000016244...

Bundgaard et al. (2004) described a hemoglobin variant with 2 amino acid substitutions: Hb S, which is a glu6-to-val substitution (G6V; 141900.0243), and Hb Agenogi, which is a glu90-to-lys substitution (G90K; 141900.0003). As the patient originated from Cameroon, the variant was designated Hb S (Cameroon). The authors stated that 4 double mutations on the same allele with the Hb S variant had previously been described: Hb S (Antilles) (141900.0244), Hb S (Providence) (141900.0246), Hb S (Oman) (141900.0245), and Hb S (Travis) (141900.0247).


.0522 HEMOGLOBIN CARDARELLI

HBB, ALA86PRO
  
RCV000016553...

In several members of a family from Naples, Italy, Pagano et al. (2004) identified a change of codon 86 of the HBB gene from GCC (ala) to CCC (pro) (A86P). The variant, which is unstable and has high oxygen affinity, was designated Hb Cardarelli. The A86P mutation had previously been found in the doubly substituted, unstable, and hyperaffine variant Hb Poissy (141900.0223), in which it occurs in combination with gly56-to-arg of Hb Hamadan (G56R; 141900.0098).


.0523 HEMOGLOBIN JAMAICA PLAIN

HBB, GLU6VAL AND LEU68PHE
  
RCV000016286...

Geva et al. (2004) described a girl of Puerto Rican descent who presented with symptomatic sickle cell disease exacerbated by mild hypoxemia, despite a newborn screening diagnosis of sickle cell trait. The child was found to be heterozygous for mutations in the HBB gene: the sickle cell mutation glu6 to val (G6V; 141900.0243), and a neutral leu68-to-phe (L68F; 141900.0524) mutation. Analysis of the patient's hemoglobin demonstrated that the doubly mutant protein, which the authors called hemoglobin Jamaica Plain (Hb JP) for Jamaica Plain, Massachusetts, had severely reduced oxygen affinity, especially in the presence of 2,3-diphosphoglycerate. Structural modeling suggested destabilization of the oxy conformation as a molecular mechanism for sickling in a heterozygote at an ambient partial pressure of oxygen. The patient's sickle cell disease was exacerbated by intercurrent respiratory infection, and she developed splenomegaly. The splenomegaly and anemia were recurrent. At the age of 19 months, during her first airplane trip, the child became acutely ill, with her spleen reaching the pelvic brim, as reported by a physician on board. After landing, she was hospitalized and found to have a hematocrit of 18%. Packed red cells were transfused; the hematocrit then rose to 28% with resolution of symptoms and a decrease in splenomegaly. Because of the apparent splenic sequestration crisis, a splenectomy was performed when she was 2 years old. Since that time, she had been asymptomatic and required no transfusions in the previous 24 months. In a commentary on the work of Geva et al. (2004), Benz (2004) noted that by itself, the L68F mutation is known as hemoglobin Rockford, a member of a class of 'low affinity hemoglobins' with reduced affinity for oxygen. These hemoglobins cause few symptoms, if any. When the L68F and G6V mutations coexist in the same beta-globin molecule, the L68F mutation causes Hb JP to desaturate easily and therefore to sickle more readily than ordinarily occurs with Hb S (G6V).


.0524 HEMOGLOBIN ROCKFORD

HBB, LEU68PHE
  
RCV000016879...

Perrault et al. (1997) described a low-affinity, stable hemoglobin variant that did not result in hemolysis, which they designated Hb Rockford; the variant is caused by a 335C-T transition in the HBB gene, resulting in a leu68-to-phe (L68F) substitution. Geva et al. (2004) described a hemoglobin variant with 2 amino acid substitutions, Hb Rockford and Hb S (G6V; 141900.0243), which they designated Hb Jamaica Plain (141900.0523).


.0525 HEMOGLOBIN TRIPOLI

HBB, GLU26ALA
  
RCV000016881

In a 5-year-old boy of Libyan origin living in Tripoli, Libya, Lacan et al. (2004) identified a change of codon 26 of the HBB gene from GAG (glu) to GCG (ala) (glu26 to ala). They designated this hemoglobin variant Hb Tripoli.


.0526 HEMOGLOBIN TIZI-OUZOU

HBB, GLY29SER
  
RCV000016882

In a 66-year-old man born in Tizi-Ouzou in northeastern Algeria, Lacan et al. (2004) described abnormal hemoglobin with change of codon 29 in the first exon of the HBB gene from GGC (gly) to AGC (ser) (gly29 to ser). The carrier showed hematologic abnormalities; the presence of microcytosis and hypochromia was explained by an additional homozygous 3.7 kb alpha(+)-thalassemic deletion.


.0527 BETA-PLUS-THALASSEMIA

HBB, 3-UNT, T-A, +3
  
RCV000016883

In a Tunisian patient with thalassemia intermedia (613985), Jacquette et al. (2004) identified compound heterozygosity for mutations in the HBB gene: a change from AATAAA to AAAAAA in the polyadenylation site of the gene and a 2-bp insertion (25insTA) in codon 9 (141900.0528), causing a frameshift with a premature termination at codon 19.


.0528 BETA-PLUS-THALASSEMIA

HBB, 2-BP INS, 25TA
  
RCV001078420...

.0529 BETA-PLUS-THALASSEMIA

HBB, 1-BP DEL, C
  
RCV001001032...

In 4 members of a Mexican family with beta-plus-thalassemia (613985), Perea et al. (2004) identified heterozygosity for a 1-bp deletion (a cytosine) in the HBB gene, resulting in a frameshift. The 1-bp deletion was either in codon 77, changing CAC (his) to CA, or in codon 78, changing CTG (leu) to TG.


.0530 BETA-PLUS-THALASSEMIA

HBB, -101C-G, PROMOTER
  
RCV000016853

The expression 'silent beta-thalassemia' (613985) is used to indicate a group of thalassemia mutations that, in the heterozygous state, are characterized by normal hematologic indices, normal or borderline HbA2 (141850) and HbF levels, and a slight imbalance of beta-globin chain synthesis (Weatherall and Clegg, 2001). These mutations are usually identified by genetic and molecular analysis of families in which a proband is affected by thalassemia intermedia resulting from a compound heterozygous state for a typical beta-thalassemia and silent beta-thalassemia. One of the most common silent beta-thalassemia mutations, described in several Mediterranean populations, is the C-to-T substitution at position -101 in the distal CACCC box (141900.0370), which leads to a moderate reduction of the expression level of the beta-globin gene. In a silent beta-thalassemia carrier of Ashkenazi Jewish descent, Moi et al. (2004) identified a C-to-G transversion at the -101 position within the distal CACCC box of the HBB gene.


.0531 HEMOGLOBIN HOKUSETSU

HBB, ASP52GLY
  
RCV000016825

During the assay of Hb A(1c) in a diabetic patient, Nakanishi et al. (1998) identified a beta-chain variant: a change of codon 52 in exon 2 of the HBB gene from asp (GAT) to gly (GGT) (asp52 to gly). The patient was hematologically normal.


.0532 HEMOGLOBIN KOCHI

HBB, LEU141VAL, LYS144TER
  
RCV000016884...

In a 53-year-old Japanese woman who underwent routine Hb A(1c) assay, Miyazaki et al. (2005) identified 2 mutations in the same HBB gene: codon 141 was changed from CTG (leu) to GTG (val) (L141V), and codon 144 was changed from AAG (lys) to TAG (stop) (K144X), leading to deletion of the last 3 amino acids of the beta-globin chain, lys-tyr-his. The increased oxygen affinity of the hemoglobin was consistent with the presence of mild erythrocytosis.


.0533 HEMOGLOBIN ZOETERWOUDE

HBB, VAL23ALA
  
RCV000016885

In a 77-year-old Dutch woman with erythrocytosis, Harteveld et al. (2005) identified heterozygosity for a GTT-to-GCT transition at codon 23 of the HBB gene, causing a valine-to-alanine (V23A) amino acid change. This was the fourth single-nucleotide substitution at codon 23 of the HBB gene and the second that was associated with erythrocytosis.


.0534 HEMOGLOBIN BREM-SUR-MER

HBB, SER9TYR
  
RCV000016858...

In a 69-year-old man, Lacan et al. (2005) identified a TCT-to-TAT transversion in codon 9 of the HBB gene, resulting in a ser9-to-tyr (S9Y) amino acid change. No hematologic abnormalities were found. The patient lived in the town of Brem-sur-Mer on the Atlantic coast of France.


.0535 HEMOGLOBIN GELDROP ST. ANNA

HBB, ASP94TYR
  
RCV000016887

Harteveld et al. (2005) observed an abnormal hemoglobin fraction during an HPLC assay for Hb A(1c) control for diabetes mellitus in a 56-year-old northern European woman. This same abnormal fraction was found in 3 of her 5 sibs and in her son. There was no history of anemia, hemolytic, or circulatory episodes. Direct sequencing of the HBB gene revealed a GAC-to-TAC transversion in heterozygous form at codon 94. They concluded that the variant is a stable hemoglobin associated with a slightly elevated oxygen affinity. Harteveld et al. (2005) noted that this was the fourth mutation known to involve the asp94 residue of the HBB gene; see 141900.0016, 141900.0035, and 141900.0045. A frameshift mutation has also been reported at this position (141900.0338).


.0536 HEMOGLOBIN MARINEO

HBB, ALA70VAL
  
RCV000016888

In a 3-generation family from western Sicily, Giambona et al. (2006) identified heterozygosity for a GCC-GTC transition in the HBB gene, resulting in an ala70-to-val (A70V) substitution. Three mutations at codon 70 of the HBB gene had been previously described, all presenting with hemolytic anemia. In the new case, no anemia or other alteration of hematologic indices was found. The family lived in the town of Marineo near Palermo, Sicily.


.0537 HEMOGLOBIN LA CORUNA

HBB, THR38ILE
  
RCV000016889

Ropero et al. (2006) described Hb La Coruna, a novel hemoglobin variant with increased oxygen affinity, leading to erythrocytosis. It is an electrophoretically silent variant that can be detected by reversed-phase high performance liquid chromatography (HPLC) and characterized by DNA sequencing. The patient was a 22-year-old Spanish male whose family lived in La Coruna in the northwest of Spain. The mother was also a carrier.


.0538 HEREDITARY PERSISTENCE OF FETAL HEMOGLOBIN

DELTA/BETA THALASSEMIA, INCLUDED
HBB, 106-KB DEL
   RCV000169772...

Kan et al. (1975) analyzed the DNA from a black patient with hereditary persistence of fetal hemoglobin (141749) and found evidence for a deletion of the beta-globin gene. Gallienne et al. (2009) cited several reports in which patients with delta/beta thalassemia (see 141749) or hereditary persistence of fetal hemoglobin had a 106-kb deletion of the beta globin gene cluster. This mutation has been designated HPFH1.


.0539 HEMOGLOBIN HANA

HBB, HIS63ASN
   RCV000855777

In a Czech proband and her sister with Heinz body hemolytic anemia (140700) and elevated levels of methemoglobin, Mojzikova et al. (2010) identified a his63-to-asn (H63N) mutation in the HBB gene. Their mother carried the same mutation but had no anemia or evidence of hemolysis. Biochemical measurements of several erythrocyte antioxidant parameters revealed decreased glutathione reductase (GSR; 138300) activity in both affected sisters but not in their asymptomatic mother. Treatment of the patients with riboflavin increased GSR activity and ameliorated clinical manifestation of Heinz body hemolytic anemia due to unstable hemoglobinopathy.


.0540 BETA-THALASSEMIA, DOMINANT INCLUSION BODY TYPE

HBB, 11-BP DEL
   RCV001549283

In a 51-year-old Spanish man with inclusion body beta-thalassemia (603902), Ropero et al. (2005) identified a heterozygous 11-basepair deletion in exon 3 of the HBB gene by direct sequencing. The deletion from codon 131 to codon 134 (-CAGAAAGTGGT) was predicted to produce a frameshift and synthesis of an abnormal and likely unstable beta-chain variant of 134 amino acids instead of the normal 146 amino acids. Inheritance could not be determined because the parents were deceased. The patient was diagnosed with beta-thalassemia in adulthood with marked siderosis, slight microcytic anemia that never needed transfusion, moderate hemolysis, subclinical jaundice, painful splenomegaly, and hepatomegaly. The patient was also homozygous for the H63D substitution in the HFE gene (613609.0002); the authors noted that the HFE variant increases the probability of developing iron overload when it is associated with beta-thalassemia, and suggested that it could contribute to siderosis.


.9999 HEMOGLOBIN BETA VARIANTS, MOLECULAR DEFECT UNKNOWN

HEMOGLOBIN CASERTA. Beta chain anomaly. See Ventruto et al. (1965) and Quattrin et al. (1970).

HEMOGLOBIN D (FRANKFURT). Beta chain anomaly. See Martin et al. (1960) and Gammack et al. (1961).

HEMOGLOBIN DURHAM-I (HEMOGLOBIN R). Beta chain anomaly. See Chernoff and Weichselbaum (1958) and Chernoff and Pettit (1964).

HEMOGLOBIN J (JAMAICA). Beta chain anomaly. See Gammack et al. (1961).

HEMOGLOBIN K. Beta chain anomaly. See O'Gorman et al. (1963).

HEMOGLOBIN KINGS COUNTY. Probably beta chain defect. Observed in an American black family. Affected persons had nonspherocytic hemolytic Heinz body anemia. See Sathiapalan and Robinson (1968).

HEMOGLOBIN L. Beta chain anomaly. See Ager and Lehmann (1957) and Gammack et al. (1961).


See Also:

Antonarakis et al. (1984); Antonarakis et al. (1982); Arous et al. (1982); Bank et al. (1980); Barwick et al. (1985); Bernards et al. (1979); Blackwell et al. (1971); Blackwell et al. (1972); Blackwell et al. (1970); Blackwell et al. (1972); Blackwell et al. (1970); Blackwell et al. (1969); Blackwell et al. (1969); Blackwell et al. (1969); Blouquit et al. (1984); Boyer et al. (1963); Brennan et al. (1977); Cai et al. (1989); Cai Yin Lin et al. (1982); Camaschella et al. (1987); Cao et al. (1981); Chang et al. (1983); Chang and Kan (1982); Charache et al. (1977); Chen et al. (1985); Chifu et al. (1992); Cole-Strauss et al. (1996); Collins et al. (1987); Ding et al. (2004); Driscoll et al. (1981); Efstratiadis et al. (1980); Enver et al. (1990); Forget (1979); Fritsch et al. (1980); Gacon et al. (1977); Garel et al. (1976); Gilbert et al. (2000); Gonzalez-Redondo et al. (1989); Gusella et al. (1979); Harano et al. (1985); Harano et al. (1990); Harano et al. (1991); Harano et al. (1990); Harano et al. (1990); Harano et al. (1983); Harano et al. (1981); Hebbel et al. (1977); Heller et al. (1966); Honig et al. (1990); Horst et al. (1983); Housman (1979); Idelson et al. (1974); Jeffreys and Flavell (1977); Johnson et al. (1980); Jones et al. (1967); Kan et al. (1977); Kan et al. (1975); Kan et al. (1980); Kaufman et al. (1980); Kohen et al. (1982); Lacombe et al. (1987); Lawn et al. (1980); Lebo et al. (1979); Li et al. (1990); Makhoul et al. (2005); Maniatis et al. (1980); Miyaji et al. (1968); Moo-Penn et al. (1977); Moo-Penn et al. (1976); Moo-Penn et al. (1977); Moo-Penn et al. (1980); Moo-Penn et al. (1978); Nakatsuji et al. (1981); Necheles et al. (1969); Novy et al. (1967); Ohba et al. (1983); Ohba et al. (1989); Ohba et al. (1985); Ohba et al. (1975); Ohta et al. (1971); Old et al. (1982); Orkin et al. (1978); Orkin et al. (1982); Orkin et al. (1980); Orkin et al. (1982); Orkin et al. (1983); Ottolenghi et al. (1976); Ottolenghi and Giglioni (1982); Ottolenghi et al. (1974); Pirastu et al. (1984); Plaseska et al. (1991); Plaseska et al. (1991); Plaseska et al. (1990); Prehu et al. (2002); Premawardhena et al. (2005); Proudfoot et al. (1980); Rahbar et al. (1981); Ricco et al. (1974); Rochette et al. (1984); Sanders-Haigh et al. (1980); Schiliro et al. (1981); Schneider et al. (1969); Scott et al. (1979); Shibata et al. (1961); Shibata et al. (1961); Smith and Conley (1959); Spritz (1981); Studencki et al. (1985); Tamagnini et al. (1983); Taylor et al. (1974); Tilghman et al. (1978); Tuan et al. (1985); Vella et al. (1967); Verma and Edwards (1978); Villegas et al. (1989); Weatherall and Clegg (1981); Williamson et al. (1983); Williamson et al. (1981); Yoon et al. (1996); Zeng and Huang (1982); Zhao et al. (1990); Zinkham et al. (1979)

REFERENCES

  1. Abourzik, N. N., Conlon, M., Zordon, G., Hine, T. K., Johnson, M. H., Jue, D. L., Moo-Penn, W. F. Hb St. Francis [beta-121(GH4)glu-to-gly]: a new mutation at the same site as Hb D-Los Angeles. Hemoglobin 15: 115-117, 1991. [PubMed: 1917532, related citations] [Full Text]

  2. Adachi, K., Surrey, S., Tamary, H., Kim, J., Eck, H. S., Rappaport, E., Ohene-Frempong, K. Hb Shelby [beta-131(H9)gln-to-lys] in association with Hb S [beta-6(A3)glu-to-val]: characterization, stability, and effects on Hb S polymerization. Hemoglobin 17: 329-343, 1993. [PubMed: 8226094, related citations] [Full Text]

  3. Adams, J. G., Boxer, L. A., Baehner, R. L., Forget, B. G., Tsistrokis, G. A., Steinberg, M. H. Hemoglobin Indianapolis: post-translational degradation of an unstable beta-chain variant producing a phenotype of severe heterozygous beta-thalassemia. (Abstract) Clin. Res. 26: 501A, 1978.

  4. Adams, J. G., Heller, P. Hemoglobin Arlington Park: a new hemoglobin variant with two amino acid substitutions in the beta chain. Hemoglobin 1: 419-426, 1977. [PubMed: 893139, related citations] [Full Text]

  5. Adams, J. G., III, Morrison, W. T., Pullen, D. J., Abney, R. L., III, Steinberg, M. H. Hemoglobin Mississippi (MS): a new hemoglobin variant with three distinct electrophoretic mobilities. (Abstract) Clin. Res. 33: 603A, 1985.

  6. Adams, J. G., III, Przywara, K. P., Heller, P., Shamsuddin, M. Hemoglobin J Altgeld Gardens, a hemoglobin variant with a substitution of the proximal histidine of the beta-chain. Hemoglobin 2: 403-415, 1978. [PubMed: 721609, related citations] [Full Text]

  7. Adams, J. G., III, Przywara, K. P., Shamsuddin, M., Heller, P. Hemoglobin J Altgeld Gardens (beta 92 (F8) his-to-asp): a new hemoglobin variant involving a substitution of the proximal histidine. (Abstract) Blood 46: 1029, 1975.

  8. Adams, J. G., III, Steinberg, M. H., Kazazian, H. H., Jr. Isolation and characterization of the translation product of a beta-globin gene nonsense mutation (beta121 GAA-to-TAA). Brit. J. Haemat. 75: 561-567, 1990. [PubMed: 2207008, related citations] [Full Text]

  9. Adams, J. G., III, Steinberg, M. H., Newman, M. V., Morrison, W. T., Benz, E. J., Jr., Iyer, R. Beta-thalassemia present in cis to a new beta-chain structural variant, Hb Vicksburg (beta-75(E19)leu-to-0). Proc. Nat. Acad. Sci. 78: 469-473, 1981. [PubMed: 6165992, related citations] [Full Text]

  10. Adams, J. G., III, Winter, W. P., Tausk, K., Heller, P. Hemoglobin Rush (beta 101 (G-3) glu-to-gln): a new unstable hemoglobin causing mild hemolytic anemia. Blood 43: 261-269, 1974. [PubMed: 4129558, related citations]

  11. Adams, J. G., Smith, C. M., Hedlund, B., Olson, M., Cich, J. A., Tukey, D. P., Steinberg, M. H. Hb North Shore: a hemoglobin variant which produces the phenotype of beta(+)-thalassemia. (Abstract) Clin. Res. 30: 499A, 1982.

  12. Adams, J. G., Steinberg, M. H., Boxer, L. A., Baehner, R. L., Forget, B. G., Tsistrakis, G. A. The structure of hemoglobin Indianapolis (beta112(G14) arginine): an unstable variant detectable only by isotopic labeling. J. Biol. Chem. 254: 3479-3482, 1979. [PubMed: 429365, related citations]

  13. Adamson, J. W., Hayashi, A., Stamatoyannopoulos, G., Burger, W. F. Erythrocyte function and marrow regulation in hemoglobin Bethesda (beta 145 histidine). J. Clin. Invest. 51: 2883-2888, 1972. [PubMed: 5080413, related citations] [Full Text]

  14. Adamson, J. W., Parer, J. T., Stamatoyannopoulos, G. Erythrocytosis associated with hemoglobin Rainier: oxygen equilibria and marrow regulation. J. Clin. Invest. 48: 1376-1386, 1969. [PubMed: 5796352, related citations] [Full Text]

  15. Agarwal, A., Guindo, A., Cissoko, Y., Taylor, J. G., Coulibaly, D., Kone, A., Kayentao, K., Djimde, A., Plowe, C. V., Doumbo, O., Wellems, T. E., Diallo, D. Hemoglobin C associated with protection from severe malaria in the Dogon of Mali, a West African population with a low prevalence of hemoglobin S. Blood 96: 2358-2363, 2000. [PubMed: 11001883, related citations]

  16. Agarwal, S., Hattori, Y., Gupta, U. R., Agarwal, S. S. A novel Indian beta-thalassemia mutation: Hb Lucknow (beta-8(A5)lys-to-arg). Hemoglobin 23: 263-265, 1999. [PubMed: 10490139, related citations] [Full Text]

  17. Ager, J. A. M., Lehmann, H. Haemoglobin L: a new haemoglobin found in a Punjabi Hindu. Brit. Med. J. 2: 142-143, 1957. [PubMed: 13436881, related citations] [Full Text]

  18. Ager, J. A. M., Lehmann, H. Observations on some 'fast' haemoglobins: K, J, N and 'Bart's'. Brit. Med. J. 1: 929-931, 1958. [PubMed: 13523233, related citations] [Full Text]

  19. Aguinaga, M. P., Wright, C. J., Roa, P. D., Terrell, F., Turner, E. A., Houston, M. Molecular diagnosis and characterization of Hb Zurich [beta-63(E7)his to arg] carriers in a Kentucky family. Hemoglobin 22: 509-515, 1998. [PubMed: 9859934, related citations] [Full Text]

  20. Ahern, E., Ahern, V., Hilton, T., Serjeant, G. R., Serjeant, B. E., Seakins, M., Lang, A., Middleton, A., Lehmann, H. Haemoglobin Caribbean beta 91(F7) leu-to-arg: a mildly unstable haemoglobin with a low oxygen affinity. FEBS Lett. 69: 99-102, 1976. [PubMed: 992050, related citations] [Full Text]

  21. Akar, E., Ozdemir, S., Timur, I. H., Akar, N. First observation of homozygous hemoglobin Hamadan (B 56 (D7) gly-arg) and beta thalassemia (-29 G-A)-hemoglobin Hamadan combination in a Turkish family. Am. J. Hemat. 74: 280-282, 2003. [PubMed: 14635211, related citations] [Full Text]

  22. Akar, N., Ozden, A., Akar, E., Cin, S., Arcasoy, A. Discrimination of Hb D Los Angeles (B121 glu-to-gln) and Hb Beograd (B121 glu-to-val) by dual restriction enzyme analysis. Am. J. Hemat. 48: 280-281, 1995. [PubMed: 7717379, related citations] [Full Text]

  23. Aksoy, M., Erdem, S., Efremov, G. D., Wilson, J. B., Huisman, T. H. J., Schroeder, W. A., Shelton, J. R., Shelton, J. B., Ulitin, O. N., Muftuoglu, A. Hemoglobin Istanbul: substitution of glutamine for histidine in a proximal histidine (F8(92)beta). J. Clin. Invest. 51: 2380-2387, 1972. [PubMed: 4639022, related citations] [Full Text]

  24. Aksoy, M., Erdem, S. Differences between individuals with hemoglobins Istanbul and Saint-Etienne (beta 92 his-to-gln). Acta Haemat. 61: 295-297, 1979. [PubMed: 111458, related citations] [Full Text]

  25. Alami, R., Greally, J. M., Tanimoto, K., Hwang, S., Feng, Y.-Q., Engel, J. D., Fiering, S., Bouhassira, E. E. Beta-globin YAC transgenes exhibit uniform expression levels but position effect variegation in mice. Hum. Molec. Genet. 9: 631-636, 2000. [PubMed: 10699186, related citations] [Full Text]

  26. Ali, M. A. M., Pinkerton, P., Chow, S. W. S., Zaetz, S. D., Wilson, J. B., Webber, B. B., Hu, H., Kutlar, A., Kutlar, F., Huisman, T. H. J. Some rare hemoglobin variants with altered oxygen affinities: Hb Linkoping (beta36(C2)pro-to-thr), Hb Caribbean (beta91(F7)leu-to-arg), and Hb Sunnybrook (beta36(C2)pro-to-arg). Hemoglobin 12: 137-148, 1988. [PubMed: 3384706, related citations] [Full Text]

  27. Allan, N., Beale, D., Irvine, D., Lehmann, H. Three haemoglobins K: Woolwich, an abnormal, Cameroon and Ibadan, two unusual variants of human haemoglobin A. Nature 208: 658-661, 1965.

  28. Allison, A. C. Protection afforded by sickle-cell trait against subtertian malarial infection. Brit. Med. J. 1: 290-294, 1954. [PubMed: 13115700, related citations] [Full Text]

  29. Altay, C., Altinoz, N., Wilson, J. B., Bolch, K. C., Huisman, T. H. J. Hemoglobin Hacettepe or alpha-2-beta-2 127(H5) gln-to-glu. Biochim. Biophys. Acta 434: 1-3, 1976. [PubMed: 938658, related citations] [Full Text]

  30. Amselem, S., Nunes, V., Vidaud, M., Estivill, X., Wong, C., d'Auriol, L., Vidaud, D., Galibert, F., Baiget, M., Goossens, M. Determination of the spectrum of beta-thalassemia genes in Spain by use of dot-blot analysis of amplified beta-globin DNA. Am. J. Hum. Genet. 43: 95-100, 1988. [PubMed: 2897787, related citations]

  31. Andersen, C. B. F., Torvund-Jensen, M., Nielsen, M. J., de Oliveira, C. L. P., Hersleth, H.-P., Andersen, N. H., Pedersen, J. S., Andersen, G. R., Moestrup, S. K. Structure of the haptoglobin-haemoglobin complex. Nature 489: 456-459, 2012. [PubMed: 22922649, related citations] [Full Text]

  32. Anderson Fernandes, B. L. Hb N-Baltimore or beta95 (FG2) lys-to-glu in Portugal. Hemoglobin 13: 83-87, 1989. [PubMed: 2703368, related citations] [Full Text]

  33. Anderson, N. L. Hemoglobin San Diego (beta 109 (G11) val-to-met). Crystal structure of the deoxy form. J. Clin. Invest. 53: 329-333, 1974. [PubMed: 4808645, related citations] [Full Text]

  34. Anderson, N. L. Hemoglobin St. Louis (beta 28 (B10) leu-to-gln): crystal structure of the fully reduced (deoxy) form. J. Clin. Invest. 58: 1107-1109, 1976. [PubMed: 993333, related citations] [Full Text]

  35. Antonarakis, S. E., Boehm, C. D., Giardina, P. J. V., Kazazian, H. H., Jr. Non-random association of the polymorphic restriction sites in the beta-globin gene cluster. Proc. Nat. Acad. Sci. 79: 137-141, 1982. [PubMed: 6275383, related citations] [Full Text]

  36. Antonarakis, S. E., Boehm, C. D., Serjeant, G. R., Theisen, C. E., Dover, G. J., Kazazian, H. H., Jr. Origin of the beta-S-globin gene in blacks: the contribution of recurrent mutation or gene conversion or both. Proc. Nat. Acad. Sci. 81: 853-856, 1984. [PubMed: 6583683, related citations] [Full Text]

  37. Antonarakis, S. E., Orkin, S. H., Cheng, T.-C., Scott, A. F., Sexton, J. P., Trusko, S., Charache, S., Kazazian, H. H., Jr. Beta-thalassemia in American blacks: novel mutations in the TATA box and an acceptor splice site. Proc. Nat. Acad. Sci. 81: 1154-1158, 1984. [PubMed: 6583702, related citations] [Full Text]

  38. Antonarakis, S. E., Orkin, S. H., Kazazian, H. H., Jr., Goff, S. C., Boehm, C. D., Waber, P. G., Sexton, J. P., Ostrer, H., Fairbanks, V. F., Chakravarti, A. Evidence for multiple origins of the beta-E-globin gene in Southeast Asia. Proc. Nat. Acad. Sci. 79: 6608-6611, 1982. [PubMed: 6292908, related citations] [Full Text]

  39. Arcasoy, A., Casey, R., Lehmann, H., Cavdar, A. O., Berki, A. A new hemoglobin J from Turkey--Hb Ankara (beta 10 ala-to-asp). FEBS Lett. 42: 121-123, 1974. [PubMed: 4850241, related citations] [Full Text]

  40. Arends, T., Castillo, O., Garlin, G., Maleh, Y., Anchustegui, M., Salazar, R. Hemoglobin Alamo (beta 19 (B1) asn-to-asp) in a Venezuelan family. Hemoglobin 11: 135-138, 1987. [PubMed: 3623973, related citations] [Full Text]

  41. Arends, T., Garlin, G., Guevara, J. M., Amesty, C., Perez-Bandez, O., Lorkin, P. A., Lehmann, H., Castillo, O. Hemoglobin Hofu associated with beta-zero-thalassemia. Acta Haemat. 73: 51-54, 1985. [PubMed: 3923770, related citations] [Full Text]

  42. Arends, T., Lehmann, H., Plowman, D., Stathopoulou, R. Haemoglobin North Shore--Caracas (beta 134 (H12) valine-to-glutamic acid). FEBS Lett. 80: 261-265, 1977. [PubMed: 891976, related citations] [Full Text]

  43. Arous, N., Braconnier, F., Thillet, J., Blouquit, Y., Galacteros, F., Chevrier, M., Bordahandy, C., Rosa, J. Hemoglobin Saint Mande beta102 (G4) asn-to-tyr: a new low oxygen affinity variant. FEBS Lett. 126: 114-116, 1981. [PubMed: 7238856, related citations] [Full Text]

  44. Arous, N., Galacteros, F., Fessas, P., Loukopoulos, D., Blouquit, Y., Komis, G., Sellaye, M., Boussiou, M., Rosa, J. Hemoglobin Knossos, beta27 ala-to-ser (B9): a new hemoglobinopathy presenting as a silent beta-thalassemia. (Abstract) Blood 60: 51A, 1982.

  45. Arous, N., Galacteros, F., Fessas, P., Loukopoulos, D., Blouquit, Y., Komis, G., Sellaye, M., Boussiou, M., Rosa, J. Structural study of hemoglobin Knossos, beta27(B9) ala-to-ser: a new abnormal hemoglobin present as a silent beta-thalassemia. FEBS Lett. 147: 247-250, 1982. [PubMed: 7173395, related citations] [Full Text]

  46. Arrizabalaga, B., Erkiaga, A., Villegas, A., Carreno, D. L. A case of Hb J-Chicago [beta-76(E20)ala-to-asp] in a Spanish family. Hemoglobin 22: 75-78, 1998. [PubMed: 9494051, related citations] [Full Text]

  47. Asakura, T., Adachi, K., Schwartz, E., Wiley, J. Molecular stability of Hb Philly (beta 35 (C1) tyr-to-phe): the relationship of hemoglobin stability to ligand state as defined by heat and mechanical shaking tests. Hemoglobin 5: 177-190, 1981. [PubMed: 7216817, related citations] [Full Text]

  48. Atweh, G. F., Anagnou, N. P., Forget, B. G., Kaufman, R. E. Beta-thalassemia resulting from a single nucleotide substitution in an acceptor splice site. Nucleic Acids Res. 13: 777-790, 1985. [PubMed: 2987809, related citations] [Full Text]

  49. Atweh, G. F., Brickner, H. E., Zhu, X.-X., Kazazian, H. H., Jr., Forget, B. G. New amber mutation in a beta-thalassemic gene with nonmeasurable levels of mutant messenger RNA in vivo. J. Clin. Invest. 82: 557-561, 1988. [PubMed: 3403716, related citations] [Full Text]

  50. Atweh, G. F., Wong, C., Reed, R., Antonarakis, S. E., Zhu, D., Ghosh, P. K., Maniatis, T., Forget, B. G., Kazazian, H. H., Jr. A new mutation in IVS-1 of the human beta-globin gene causing beta-thalassemia due to abnormal splicing. Blood 70: 147-151, 1987. [PubMed: 2439149, related citations]

  51. Aulehla-Scholz, C., Spiegelberg, R., Horst, J. A beta-thalassemia mutant caused by a 300-bp deletion in the human beta-globin gene. Hum. Genet. 81: 298-299, 1989. [PubMed: 2921044, related citations] [Full Text]

  52. Badens, C., Mattei, M. G., Imbert, A. M., Lapoumeroulie, C., Martini, N., Michel, G., Lena-Russo, D. A novel mechanism for thalassaemia intermedia. Lancet 359: 132-133, 2002. [PubMed: 11809258, related citations] [Full Text]

  53. Badr, F. M., Lorkin, P. A., Lehmann, H. Haemoglobin P-Nilotic, containing a beta-delta chain. Nature N.B. 242: 107-110, 1973. [PubMed: 4513408, related citations] [Full Text]

  54. Baglioni, C., Ingram, V. M. Four adult haemoglobin types in one person. Nature 189: 465-467, 1961. [PubMed: 13685866, related citations] [Full Text]

  55. Baiget, M., Gomez Pereira, C., Jue, D. L., Johnson, M. H., McGuffey, J. E., Moo-Penn, W. F. A case of hemoglobin Indianapolis (beta112(G14) cys-to-arg) in an individual from Cordoba, Spain. Hemoglobin 10: 483-494, 1986. [PubMed: 3781865, related citations] [Full Text]

  56. Baine, R. M., Wright, J. M., Johnson, M. H., Cadena, C. L. Biosynthetic evidence for instability of Hb M Saskatoon. Hemoglobin 4: 201-207, 1980. [PubMed: 6248489, related citations] [Full Text]

  57. Baird, M., Driscoll, C., Schreiner, H., Sciarratta, G. V., Sansone, G., Niazi, G., Ramirez, F., Bank, A. A nucleotide change at a splice junction in the human beta-globin gene is associated with beta-zero-thalassemia. Proc. Nat. Acad. Sci. 78: 4218-4221, 1981. [PubMed: 6270663, related citations] [Full Text]

  58. Baklouti, F., Giraud, Y., Francina, A., Richard, G., Favre-Gilly, J., Delaunay, J. Hemoglobin Pierre-Benite (beta90 (F6) glu-to-asp), a new high affinity variant found in a French family. Hemoglobin 12: 171-177, 1988. [PubMed: 3384709, related citations] [Full Text]

  59. Baklouti, F., Giraud, Y., Francina, A., Richard, G., Perier, C., Geyssant, A., Jaubert, J., Brizard, C., Delaunay, J. Hemoglobin Grange-Blanche (beta27 (B9) ala-to-val), a new variant with normal expression and increased affinity for oxygen. FEBS Lett. 223: 59-62, 1987. [PubMed: 3666141, related citations] [Full Text]

  60. Ballas, S. K., Lewis, C. N., Noone, A. M., Krasnow, S. H., Kamarulzaman, E., Burka, E. R. Clinical, hematological, and biochemical features of Hb SC disease. Am. J. Hemat. 13: 37-51, 1982. [PubMed: 7137165, related citations] [Full Text]

  61. Ballas, S. K., Park, D. K. Biosynthetic evidence for stability of Hb N-Baltimore. Hemoglobin 9: 489-494, 1985. [PubMed: 4086303, related citations] [Full Text]

  62. Baltzan, D. M., Sugarman, H. Hereditary cyanosis. Canad. Med. Assoc. J. 62: 348-350, 1950. [PubMed: 20324533, related citations]

  63. Bank, A., Mears, J. G., Ramirez, F., Burns, A. L., Spence, S., Feldenzer, J., Baird, M. The organization of the gamma-delta-beta gene complex in normal and thalassemia cells. Hemoglobin 4: 497-507, 1980. [PubMed: 6252123, related citations] [Full Text]

  64. Barany, F. Genetic disease detection and DNA amplification using cloned thermostable ligase. Proc. Nat. Acad. Sci. 88: 189-193, 1991. [PubMed: 1986365, related citations] [Full Text]

  65. Barbosa, C. A. A., Koury, W. H., Krieger, H. Linkage data on MN and the Hb beta locus. Am. J. Hum. Genet. 27: 797-801, 1975. [PubMed: 1200031, related citations]

  66. Bardakdjian, J., Arous, N., Kister, J., Blouquit, Y., Giacomini, T., Lacombe, C., Riou, J., Hafsia, R., Rosa, J., Galacteros, F. Further characterization of Hb Henri Mondor or beta26(B8)glu-to-val. Hemoglobin 11: 1-11, 1987. [PubMed: 3583762, related citations] [Full Text]

  67. Bardakdjian, J., Kister, J., Rhoda, M. D., Marden, M., Arous, N., De Leon, J., North, M. L., Lacombe, C., Blouquit, Y., Castracane, C., Riou, J., Rosa, J., Galacteros, F. Hb J-Cordoba (beta95(FG2)lys-to-met): a new Hb variant found in Argentina. Hemoglobin 12: 1-11, 1988. [PubMed: 3384693, related citations] [Full Text]

  68. Bardakdjian, J., Leclerc, L., Blouquit, Y., Oules, O., Rafaillat, D., Arous, N., Bohn, B., Poyart, C., Rosa, J., Galacteros, F. A new case of hemoglobin Providence (beta82 (EF6) lys-to-asn or asp) discovered in a French Caucasian family: structural and functional studies. Hemoglobin 9: 333-348, 1985. [PubMed: 3935609, related citations] [Full Text]

  69. Bardakdjian-Michau, J., Fucharoen, S., Delanoe-Garin, J., Kister, J., Lacombe, C., Winichagoon, P., Blouquit, Y., Riou, J., Wasi, P., Galacteros, F. Hemoglobin Dhonburi beta126 (H4) val-to-gly: a new unstable beta variant producing a beta-thalassemia intermedia phenotype in association with beta-zero-thalassemia. Am. J. Hemat. 35: 96-99, 1990. [PubMed: 2399911, related citations] [Full Text]

  70. Bare, G. H., Bromberg, P. A., Alben, J. O., Brimhall, B., Jones, R. T., Mintz, S., Rother, I. Altered C-terminal salt bridges in haemoglobin York cause high oxygen affinity. Nature 259: 155-156, 1976. [PubMed: 1246355, related citations] [Full Text]

  71. Barwick, R. C., Head, C. G., Hih, M. F.-C., Block, S. H., Jones, R. T. Hb T-Cambodia (beta26 (B8) glu-to-lys, beta121 (GH4) glu-to-gln) a new doubly substituted beta globin variant found in a Cambodian family. (Abstract) Blood 66: 68A, 1985.

  72. Barwick, R. C., Jones, R. T., Head, C. G., Shih, M. F.-C., Prchal, J. T., Shih, D. T.-B. Hb Long Island: a hemoglobin variant with a methionyl extension at the NH2 terminus and a prolyl substitution for the normal histidyl residue 2 of the beta chain. Proc. Nat. Acad. Sci. 82: 4602-4605, 1985. [PubMed: 3860812, related citations] [Full Text]

  73. Bauchwitz, R., Costantini, F. Developmentally distinct effects on human epsilon-, gamma- and delta-globin levels caused by the absence or altered position of the human beta-globin gene in YAC transgenic mice. Hum. Molec. Genet. 9: 561-574, 2000. [PubMed: 10699179, related citations] [Full Text]

  74. Baudin-Chich, V., Wajcman, H., Gombaud-Saintonge, G., Arous, N., Riou, J., Briere, J., Galacteros, F. Hemoglobin Brest (beta127 (H5) gln-to-lys): a new unstable human hemoglobin variant located at the alpha-1/beta-1 interface with specific electrophoretic behavior. Hemoglobin 12: 179-188, 1988. [PubMed: 3384710, related citations] [Full Text]

  75. Baur, E. W., Motulsky, A. G. Hemoglobin Tacoma, a beta-chain variant associated with increased Hb A(2). Humangenetik 1: 621-634, 1965. [PubMed: 5869485, related citations]

  76. Baysal, E., Carver, M. F. H. The beta- and delta-thalassemia repository (eighth edition). Hemoglobin 19: 213-236, 1995. [PubMed: 7558879, related citations] [Full Text]

  77. Beldjord, C., Lapoumeroulie, C., Pagnier, J., Benabadji, M., Krishnamoorthy, R., Labie, D., Bank, A. A novel beta-thalassemia gene with a single base mutation in the conserved polypyrimidine sequence at the 3-prime end of IVS-II. Nucleic Acids Res. 16: 4927-4935, 1988. [PubMed: 3387213, related citations] [Full Text]

  78. Bento, M. C., Ribeiro, M. L., Cunha, E., Rebelo, U., Granjo, E., Granado, C., Tamagnini, G. P. Hb Vila Real (beta-36(C2)pro-to-his): a newly discovered high oxygen affinity variant. Hemoglobin 24: 59-63, 2000. [PubMed: 10722117, related citations] [Full Text]

  79. Benz, E. J., Jr., Berman, B. W., Tonkonow, B. L., Coupal, E., Coates, T., Boxer, L. A., Altman, A., Adams, J. G., III. Molecular analysis of the beta-thalassemia phenotype associated with inheritance of hemoglobin E (alpha-2-beta-2(26) glu-to-lys). J. Clin. Invest. 68: 118-126, 1981. [PubMed: 6166632, related citations] [Full Text]

  80. Benz, E. J., Jr. Genotypes and phenotypes--another lesson from the hemoglobinopathies. New Eng. J. Med. 351: 1490-1492, 2004. Note: Erratum: New Eng. J. Med. 352: 524 only, 2005. [PubMed: 15470211, related citations] [Full Text]

  81. Benzer, S., Ingram, V. M., Lehmann, H. Three varieties of human haemoglobin D. Nature 182: 852-854, 1958. [PubMed: 13590135, related citations] [Full Text]

  82. Beresford, C. H., Clegg, J. B., Weatherall, D. J. Haemoglobin Ocho Rios (beta 52 (D3) aspartic acid to alanine): a new beta chain variant of haemoglobin A found in combination with haemoglobin S. J. Med. Genet. 9: 151-153, 1972. [PubMed: 5046622, related citations] [Full Text]

  83. Berglund, S., Linell, F. Fibrosis and carcinoma of the lung in a family with haemoglobin Malmo--anatomic findings. Scand. J. Haemat. 9: 424-432, 1972. [PubMed: 4342316, related citations] [Full Text]

  84. Berglund, S. Erythrocytosis associated with haemoglobin Malmo, accompanied by pulmonary changes, occurring in the same family. Scand. J. Haemat. 9: 355-369, 1972. [PubMed: 5073564, related citations] [Full Text]

  85. Beris, P., Darbellay, R., Speiser, D., Kirchner, V., Miescher, P. A. De novo initiation codon mutation (ATG-to-ACG) of the beta-globin gene causing beta-thalassemia in a Swiss family. Am. J. Hemat. 42: 248-253, 1993. [PubMed: 8094943, related citations] [Full Text]

  86. Beris, P. H., Miescher, P. A., Diaz-Chico, J. C., Hans, I. S., Kutlar, A., Hu, H., Wilson, J. B., Huisman, T. H. J. Inclusion-body beta-thalassemia trait in a Swiss family is caused by an abnormal hemoglobin (Geneva) with an altered and extended beta chain carboxy-terminus due to a modification in codon beta-114. Blood 72: 801-805, 1988. [PubMed: 3401599, related citations]

  87. Berlin, G., Wranne, B., Jeppsson, J.-O. Hb Linkoping (beta36 pro-to-thr): a new high oxygen affinity hemoglobin variant found in two families of Finnish origin. Europ. J. Haemat. 39: 452-456, 1987. [PubMed: 3691763, related citations] [Full Text]

  88. Berlin, G., Wranne, B. HB Olympia (beta-20(B2)val-to-met) in a Swedish family. Hemoglobin 13: 493-495, 1989. [PubMed: 2599884, related citations] [Full Text]

  89. Bernards, R., Little, P. F. R., Annison, G., Williamson, R., Flavell, R. A. Structure of the human G-gamma-A-gamma-delta-beta-globin gene locus. Proc. Nat. Acad. Sci. 76: 4827-4831, 1979. [PubMed: 291902, related citations] [Full Text]

  90. Bernini, L. F., Giordano, P. C. Hemoglobin Tilburg: beta 73 (E17) asp-to-gly: a new hemoglobin with reduced oxygen affinity. Biochim. Biophys. Acta 957: 281-285, 1988. [PubMed: 3191145, related citations] [Full Text]

  91. Betke, K., Kleihauer, E., Gehring-Muller, R., Braunitzer, G., Jacobi, J., Schmidt, D. Hb M Hamburg, eine beta-Ketten-Anomalie: beta (63 tyr). Klin. Wschr. 44: 961-966, 1966. [PubMed: 5996551, related citations] [Full Text]

  92. Beutler, E., Gelbart, T., Demina, A. Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc. Nat. Acad. Sci. 95: 8170-8174, 1998. [PubMed: 9653159, images, related citations] [Full Text]

  93. Beutler, E., Lang, A., Lehmann, H. Hemoglobin Duarte (beta 62 ala-to-pro): a new unstable hemoglobin with increased oxygen affinity. Blood 43: 527-536, 1974. [PubMed: 4361395, related citations]

  94. Beuzard, Y., Basset, P., Braconnier, F., El Gammal, H., Martin, L., Oudart, J. L., Thillet, J. Haemoglobin Saki beta 14 leu-to-pro: structure and function. Biochim. Biophys. Acta 393: 182-187, 1975. [PubMed: 237566, related citations] [Full Text]

  95. Beuzard, Y., Courvalin, J. C., Solal, M. C., Garel, M. C., Rosa, J., Brizard, C. P., Gibaud, A. Structural studies of Hb St. Etienne beta 92 (F8) his-to-gln: a new abnormal hemoglobin with loss of beta proximal histidine and absence of heme on the beta chains. FEBS Lett. 27: 76-80, 1972. [PubMed: 11946811, related citations] [Full Text]

  96. Birben, E., Oner, R., Oner, C., Gumruk, F., Gurgey, A., Altay, C. Homozygosity for Hb E-Saskatoon (beta-22(B4)glu-to-lys) in a Turkish patient. Hemoglobin 25: 409-415, 2001. [PubMed: 11791874, related citations] [Full Text]

  97. Bircan, I., Guven, A. G., Yegin, O., Plaseska, D., Wilson, J. B., Ramachandran, M., Huisman, T. H. J. Hb N-Baltimore [beta95(FG2)lys-to-glu] and Hb J-Iran [beta77(EF1)his-to-asp] observed in a Turkish family from Antalya. Hemoglobin 14: 453-457, 1990. [PubMed: 2283300, related citations] [Full Text]

  98. Bird, A. R., Elliot, T. E., Wilson, J. B., Webber, B. B., Kutlar, F., Kutlar, A., Huisman, T. H. J. Hb Boras or beta88 (F4) leu-to-arg in a South African female. Hemoglobin 11: 157-160, 1987. [PubMed: 3623976, related citations] [Full Text]

  99. Bird, A. R., Kent, P., Moores, P. P., Elliott, T. Haemoglobin M-Hyde Park associated with polyagglutinable red blood cells in a South African family. Brit. J. Haemat. 68: 459-464, 1988. [PubMed: 3377987, related citations] [Full Text]

  100. Bisse, E., Schlemer, E., Lizama, M., Huaman-Guillen, P., Wieland, H., Adam, G., Molchanova, T. P., Huisman, T. H. J. Hb Strasbourg [beta-23(B5)val-to-asp]: a high oxygen affinity variant observed in a German family. Hemoglobin 22: 69-73, 1998. [PubMed: 9494050, related citations] [Full Text]

  101. Bisse, E., Wieland, H., Ritschel, H. A case of the Hb Regina (beta96 (FG3) leu-to-val) in a German male associated with high oxygen affinity and erythrocytosis. Acta Haemat. 85: 212-216, 1991. [PubMed: 1853685, related citations] [Full Text]

  102. Bisse, E., Zorn, N., Heinrichs, I., Eigel, A., Van Dorsselaer, A., Wieland, H., Kister, J., Marden, M. C. Characterization of a new electrophoretically silent hemoglobin variant: Hb Saale or alpha-2,beta-2 84(EF8)thr-to-ala. J. Biol. Chem. 275: 21380-21384, 2000. [PubMed: 10770934, related citations] [Full Text]

  103. Blackwell, R. Q., Huang, J. T. H., Ro, I. H. Hemoglobin variants in Koreans: hemoglobin G (Taegu). Science 158: 1056-1057, 1967. [PubMed: 6054484, related citations] [Full Text]

  104. Blackwell, R. Q., Jim, R. T. S., Liu, C.-S., Weng, M. I., Wang, C.-L., Shih, T.-B. Fast hemoglobin variant found in Hawaiian-Chinese-Caucasian family in Hawaii and a Chinese subject in Taiwan. Vox Sang. 22: 469-473, 1972. [PubMed: 5032420, related citations] [Full Text]

  105. Blackwell, R. Q., Liu, C. S., Lie-Injo, L. E., Pribadi, W. Fast hemoglobin variant in Minahassan people of Sulawesi, Chinese and Thais: beta56 gly-to-asp. Am. J. Phys. Anthrop. 32: 147-150, 1970. [PubMed: 5415584, related citations] [Full Text]

  106. Blackwell, R. Q., Liu, C. S., Shih, T. B. Hemoglobin J Kaohsiung: beta 59 lys-to-thr. Biochim. Biophys. Acta 229: 343-348, 1971. [PubMed: 5553980, related citations] [Full Text]

  107. Blackwell, R. Q., Liu, C. S., Wang, C. L. Hemoglobin Siriraj, beta 7 (A4) glu-to-lys, in a Chinese subject in Taiwan. Vox Sang. 23: 433-438, 1972. [PubMed: 5077741, related citations] [Full Text]

  108. Blackwell, R. Q., Liu, C. S., Yang, H. J., Wang, C. C., Huang, J. T. H. Hemoglobin variant common to Chinese and North American Indians: beta22 glu-to-ala. Science 161: 381-382, 1968. [PubMed: 5658717, related citations] [Full Text]

  109. Blackwell, R. Q., Liu, C. S. The identical structural anomalies of hemoglobin J(Meinung) and J(Korat). Biochem. Biophys. Res. Commun. 24: 732-738, 1966. [PubMed: 5970505, related citations] [Full Text]

  110. Blackwell, R. Q., Liu, C. S. Hemoglobin G Taiwan-Ami: beta 25 gly-to-arg. Biochem. Biophys. Res. Commun. 30: 690-696, 1968. [PubMed: 5642385, related citations] [Full Text]

  111. Blackwell, R. Q., Liu, C.-S., Wang, C.-L. Hemoglobin Ta-Li: beta 83 gly-to-cys. Biochim. Biophys. Acta 243: 467-474, 1971. [PubMed: 5129589, related citations]

  112. Blackwell, R. Q., Oemijati, S., Pribadi, W., Weng, M. I., Liu, C. S. Hemoglobin G (Makassar): beta 6 glu-to-ala. Biochim. Biophys. Acta 214: 396-401, 1970. [PubMed: 5509617, related citations]

  113. Blackwell, R. Q., Ro, I. H., Liu, C. S., Yang, H. J., Wang, C. C., Huang, J. T. H. Hemoglobin variant found in Koreans, Chinese, and North American Indians: beta 22 glu-to-ala. Am. J. Phys. Anthrop. 30: 389-391, 1969. [PubMed: 5791015, related citations] [Full Text]

  114. Blackwell, R. Q., Shih, T.-B., Wang, C.-L., Liu, C.-S. Hemoglobin G(Hsi-Tsou): beta 79 asp-to-gly. Biochim. Biophys. Acta 257: 49-53, 1972. [PubMed: 5009835, related citations] [Full Text]

  115. Blackwell, R. Q., Yang, H. J., Liu, C. S., Wang, C. C. Structural identification of haemoglobin E in Filipinos. Trop. Geogr. Med. 22: 112-114, 1970. [PubMed: 5435932, related citations]

  116. Blackwell, R. Q., Yang, H. J., Wang, C. C. Hemoglobin G (Szuhu): beta 80 asn replaced by lys. Biochim. Biophys. Acta 188: 59-64, 1969. [PubMed: 5820686, related citations] [Full Text]

  117. Blackwell, R. Q., Yang, H. J., Wang, C. C. Hemoglobin G-Taipei: beta 22 glu replaced by gly. Biochim. Biophys. Acta 175: 237-241, 1969. [PubMed: 5778166, related citations]

  118. Blackwell, R. Q., Yang, H.-J., Wang, C.-C. Hemoglobin J Taichung: beta129 ala-to-asp. Biochim. Biophys. Acta 194: 1-5, 1969. [PubMed: 5353125, related citations]

  119. Blanke, S., Johnsen, A., Wimberley, P. D., Mortensen, H. B. Hemoglobin Hafnia: alpha-2(beta116 (G18) his-to-gln); a new hemoglobin variant mistaken for glycated hemoglobin. Biochim. Biophys. Acta 955: 214-219, 1988. [PubMed: 3395624, related citations] [Full Text]

  120. Blanke, S., Johnsen, A., Wimberley, P. D. HB Volga (beta-27(B9)ala-to-asp), a possible de novo mutation in a Danish person. Hemoglobin 13: 489-491, 1989. [PubMed: 2599883, related citations] [Full Text]

  121. Blibech, R., Mrad, H., Kastally, R., Brissart, M. A., Potron, G., Arous, N., Riou, J., Blouquit, Y., Bardakdjian, J., Lacombe, C., Rosa, J., Galacteros, F. Hemoglobin Beirut (beta 126 val-to-ala) in an Algerian family. Hemoglobin 10: 651-654, 1986. [PubMed: 3557996, related citations] [Full Text]

  122. Blom van Assendelft, G., Hanscombe, O., Grosveld, F., Greaves, D. R. The beta-globin dominant control region activates homologous and heterologous promoters in a tissue-specific manner. Cell 56: 969-977, 1989. [PubMed: 2924354, related citations] [Full Text]

  123. Blouquit, Y., Arous, N., Lena, D., Delanoe-Garin, J., Lacombe, C., Bardakdjian, J., Vovan, L., Orsini, A., Rosa, J., Galacteros, F. Hb Marseille (beta N methionyl-2 (NA-2) his-to-pro): a new beta chain variant having an extended N-terminus. FEBS Lett. 178: 315-318, 1984. [PubMed: 6548977, related citations] [Full Text]

  124. Blouquit, Y., Arous, N., Machado, P. E. A., Garel, M. C. Hb Henri Mondor: beta 26(B8) glu-to-val: a variant with a substitution localized at the same position as that of Hb E beta 26 glu-to-lys. FEBS Lett. 72: 5-7, 1976. [PubMed: 1001469, related citations] [Full Text]

  125. Blouquit, Y., Bardakdjian, J., Lena-Russo, D., Arous, N., Perrimond, H., Orsini, A., Rosa, J., Galacteros, F. HB Bruxelles: beta-41 or 42(C7 or CD1)phe deleted. Hemoglobin 13: 465-474, 1989. [PubMed: 2599881, related citations] [Full Text]

  126. Blouquit, Y., Braconnier, F., Cohen-Solal, M., Foldi, J., Arous, N., Ankri, A., Binet, J. L., Rosa, J. Hemoglobin Pitie-Salpetriere beta 34 (B16) val-to-phe: a new high oxygen affinity variant associated with familial erythrocytosis. Biochim. Biophys. Acta 624: 473-478, 1980. [PubMed: 7417488, related citations] [Full Text]

  127. Blouquit, Y., Braconnier, F., Galacteros, F., Arous, N., Soria, J., Zittoun, R., Rosa, J. Hemoglobin Hotel-Dieu, beta-99 asp-to-gly (G1): a new abnormal hemoglobin with high oxygen affinity. Hemoglobin 5: 19-31, 1981. [PubMed: 7204092, related citations] [Full Text]

  128. Blouquit, Y., Delanoe-Garin, J., Lacombe, C., Arous, N., Cayre, Y., Peduzzi, J., Braconnier, F., Galacteros, F. Structural study of hemoglobin Hazebrouck, beta38(C4)thr-to-pro: a new abnormal hemoglobin with instability and low oxygen affinity. FEBS Lett. 172: 155-158, 1984. Note: Abstract: Hemoglobin 9: 106-107, 1985. [PubMed: 6430717, related citations] [Full Text]

  129. Blouquit, Y., Lena-Russo, D., Delanoe, J., Arous, N., Bardakjian, J., Lacombe, C., Vovan, L., Orsini, A., Rosa, J., Galacteros, F. Hb Marseille beta-1(A1)NH2-met, 2(A2)his-to-3(A3)pro: first variant having a N-terminal elongated beta chain. (Abstract) Hemoglobin 9: 107-108, 1985.

  130. Boehm, C. D., Dowling, C. E., Antonarakis, S. E., Honig, G. R., Kazazian, H. H., Jr. Evidence supporting a single origin of the beta(C)-globin gene in blacks. Am. J. Hum. Genet. 37: 771-777, 1985. [PubMed: 9556665, related citations]

  131. Boehm, C. D., Dowling, C. E., Waber, P. G., Giardina, P. J. V., Kazazian, H. H., Jr. Use of oligonucleotide hybridization in the characterization of a beta-zero-thalassemia gene (beta37 TGG-to-TGA) in a Saudi Arabian family. Blood 67: 1185-1188, 1986. Note: Erratum: Blood 68: 323 only, 1986. [PubMed: 3006832, related citations]

  132. Bogoevski, P., Efremov, G. D., Kezic, J., Lam, H., Wilson, J. B., Huisman, T. H. J. Hb Sabine or beta 91(F7) leu-to-pro in a Yugoslavian boy. Hemoglobin 7: 195-200, 1983. [PubMed: 6671906, related citations]

  133. Boi, S., Hendy, J., Goodall, I., Gilbert, A., Fleming, P., Hughes, W. G. First report of HB Long Island-Marseille in Australia--a chance discovery. Hemoglobin 13: 515-520, 1989. [PubMed: 2599888, related citations] [Full Text]

  134. Boissel, J. P., Wajcman, H., Fabritius, H., Cabannes, R., Labie, D. Application of high-performance liquid chromatography to abnormal hemoglobin studies. Characterization of hemoglobin D in Ivory Coast and description of a new variant, Hb Cocody (beta 21 asp leads to asn). Biochim. Biophys. Acta 670: 203-206, 1981. [PubMed: 6271242, related citations] [Full Text]

  135. Boissel, J. P., Wajcman, H., Labie, D., Fabritius, H., Cabannes, R. Hb J Daloa (beta 57 (E1) asn replaced by asp): a new variant found in Ivory Coast. Hemoglobin 6: 433-437, 1982. [PubMed: 6292136, related citations] [Full Text]

  136. Boissel, J.-P., Kasper, T. J., Shah, S. C., Malone, J. I., Bunn, H. F. Amino-terminal processing of proteins: hemoglobin South Florida, a variant with retention of initiator methionine and N(alpha)-acetylation. Proc. Nat. Acad. Sci. 82: 8448-8452, 1985. [PubMed: 3866233, related citations] [Full Text]

  137. Bonaventura, C., Cashon, R., Bonaventura, J., Perutz, M., Fermi, G., Shih, D. T.-B. Involvement of the distal histidine in the low affinity exhibited by Hb Chico (lys-beta66-to-thr) and its isolated beta chains. J. Biol. Chem. 266: 23033-23040, 1991. [PubMed: 1744099, related citations]

  138. Bonaventura, J., Riggs, A. Polymerization of hemoglobins of mouse and man: structural basis. Science 158: 800-802, 1967. [PubMed: 6048124, related citations] [Full Text]

  139. Bonaventura, J., Riggs, A. Hemoglobin Kansas, a human hemoglobin with a neutral amino acid substitution and an abnormal oxygen equilibrium. J. Biol. Chem. 243: 980-991, 1968. [PubMed: 5640981, related citations]

  140. Bookchin, R. M., Davis, R. P., Ranney, H. M. Clinical features of hemoglobin C(Harlem), a new sickling hemoglobin variant. Ann. Intern. Med. 68: 8-18, 1968.

  141. Bookchin, R. M., Nagel, R. L., Ranney, H. M., Jacobs, A. S. Hemoglobin C (Harlem): a sickling variant containing amino acid substitutions in two residues of the beta-polypeptide chain. Biochem. Biophys. Res. Commun. 23: 122-127, 1966. [PubMed: 5928902, related citations] [Full Text]

  142. Bookchin, R. M., Nagel, R. L., Ranney, H. M. The effect of beta 73 asn on the interactions of sickling hemoglobins. Biochim. Biophys. Acta 221: 373-375, 1970. [PubMed: 5490239, related citations] [Full Text]

  143. Bottardi, S., Bourgoin, V., Pierre-Charles, N., Milot, E. Onset and inheritance of abnormal epigenetic regulation in hematopoietic cells. Hum. Molec. Genet. 14: 493-502, 2005. [PubMed: 15615768, related citations] [Full Text]

  144. Bouhass, R., Aguercif, M., Trabuchet, G., Godet, J. A new mutation at IVS1 nt 2(T-to-A), in beta-thalassemia from Algeria. (Letter) Blood 76: 1054-1055, 1990. [PubMed: 2393712, related citations]

  145. Boulton, F. E., Huntsman, R. G., Lehmann, H., Lorkin, P., Romero-Herrera, A. E. Myoglobin variants. (Abstract) Biochem. J. 118: 39P, 1970.

  146. Bowman, B. H., Barnett, D. R., Hite, R. Hemoglobin G (Coushatta): a beta variant with a delta-like substitution. Biochem. Biophys. Res. Commun. 26: 466-470, 1967. [PubMed: 6033745, related citations] [Full Text]

  147. Bowman, B. H., Moreland, H., Schneider, R. G. A new haemoglobin variant (G-Galveston). Nature 193: 1298-1300, 1962.

  148. Bowman, B. H., Oliver, C. P., Barnett, D. R., Cunningham, J. E., Schneider, R. G. Chemical characterization of three hemoglobins G. Blood 23: 193-199, 1964.

  149. Bowman, R., Ingram, V. M. Abnormal human haemoglobin. VII. The comparison of normal human haemoglobin and haemoglobin D (Chicago). Biochim. Biophys. Acta 53: 569-573, 1961. [PubMed: 13872094, related citations] [Full Text]

  150. Boyer, S. H., Charache, S., Fairbanks, V. F., Maldonado, J. E., Noyes, A., Gayle, E. E. Hemoglobin Malmo beta-97 (FG-4) histidine to glutamine: a cause of polycythemia. J. Clin. Invest. 51: 666-676, 1972. [PubMed: 5011106, related citations] [Full Text]

  151. Boyer, S. H., Rucknagel, D. L., Weatherall, D. J., Watson-Williams, E. J. Further evidence for linkage between the beta and gamma loci governing human hemoglobin and the population dynamics of linked genes. Am. J. Hum. Genet. 15: 438-448, 1963. [PubMed: 14097238, related citations]

  152. Brabec, V., Indrak, K., Fortova, H., Suttnar, J., Blazek, B., Cermak, J., Divoky, V., Veprekova, L., Zeman, J. Hb Nottingham or beta 98 (FG5) val-to-gly in a Czech child. Ann. Hemat. 69: 93-95, 1994. [PubMed: 8080886, related citations] [Full Text]

  153. Bradley, T. B., Jr., Wohl, R. C., Rieder, R. F. Hemoglobin Gun Hill: deletion of five amino acid residues and impaired heme-globin binding. Science 157: 1581-1583, 1967. [PubMed: 6038175, related citations] [Full Text]

  154. Bradley, T. B., Wohl, R. C., Murphy, S. B., Oski, F. A., Bunn, H. F. Properties of hemoglobin Bryn Mawr, beta85 phe-to-ser, a new spontaneous mutation producing an unstable hemoglobin with high oxygen affinity. (Abstract) Blood 40: 947, 1972.

  155. Bradley, T. B., Wohl, R. C., Petz, L. D., Perkins, H. A., Reynolds, R. D. Possible gonadal mosaicism in a family with hemoglobin Koln. Johns Hopkins Med. J. 146: 236-240, 1980. [PubMed: 7382247, related citations]

  156. Brancati, C., Caracciolo, M., Bria, M., Bisconte, M. G., Qualtieri, A. HB G-San Jose homozygosis in a Calabrian family. Hemoglobin 13: 497-503, 1989. [PubMed: 2599885, related citations] [Full Text]

  157. Bratu, V., Lorkin, P. A., Lehmann, H., Predescu, C. Haemoglobin Bucuresti (beta 42 (CD1) phe-to-leu), a cause of unstable haemoglobin haemolytic anaemia. Biochim. Biophys. Acta 251: 1-6, 1971. [PubMed: 5133275, related citations] [Full Text]

  158. Brennan, S. O., Arnold, B., Fleming, P., Carrell, R. W. A new unstable haemoglobin, beta 134: val-to-glu. Proc. New Zeal. Med. J. 85: 398-399, 1977.

  159. Brennan, S. O., Jones, K. O., Crethar, L., Arnold, B. J., Fleming, P. J., Winterbourn, C. C. Haemoglobin North Shore, beta134 val replaced by glu, a new unstable haemoglobin. Biochim. Biophys. Acta 494: 403-407, 1977. [PubMed: 199272, related citations] [Full Text]

  160. Brennan, S. O., Potter, H. C., Kubala, L. M., Carnoutsos, S. A., Ferguson, M. M. Hb Canterbury (beta-112(G14)cys-to-phe): a new, mildly unstable variant. Hemoglobin 26: 67-69, 2002. [PubMed: 11939514, related citations] [Full Text]

  161. Brennan, S. O., Shaw, J., Allen, J., George, P. M. Beta-141 leu is not deleted in the unstable haemoglobin Atlanta-Coventry but is replaced by a novel amino acid of mass 129 daltons. Brit. J. Haemat. 81: 99-103, 1992. [PubMed: 1520632, related citations] [Full Text]

  162. Brennan, S. O., Wells, R. M., Smith, H., Carrell, R. W. Hemoglobin Brisbane: beta68 leu-to-his: a new high oxygen affinity variant. Hemoglobin 5: 325-335, 1981. [PubMed: 6166590, related citations] [Full Text]

  163. Brennan, S. O., Williamson, D., Symmans, W. A., Carrell, R. W. Two unstable hemoglobins in one individual: Hb Atlanta (beta75 leu-to-pro) and Hb Coventry (beta 141 leu deleted). Hemoglobin 7: 303-312, 1983. [PubMed: 6618886, related citations] [Full Text]

  164. Brennan, S. O., Williamson, D., Symmans, W. A., Carrell, R. W. Two de novo mutations in one beta globin chain: hemoglobin Atlanta-Coventry, beta75 leu-to-pro and beta141 deleted. Hemoglobin 10: 225-237, 1986. [PubMed: 3710819, related citations] [Full Text]

  165. Brennan, S. O., Williamson, D., Whisson, M. E., Carrell, R. W. Hemoglobin Palmerston North, beta23 (B5) val-to-phe: a new variant identified in a patient with polycythemia. Hemoglobin 6: 569-575, 1982. [PubMed: 7161106, related citations] [Full Text]

  166. Brimhall, B., Jones, R. T., Baur, E. W., Motulsky, A. G. Structural characterization of hemoglobin Tacoma. Biochemistry 8: 2125-2129, 1969. [PubMed: 5785231, related citations] [Full Text]

  167. Brimhall, B., Jones, T. T., Schneider, R. G., Hosty, T. S., Tomlin, G., Atkins, R. Two new hemoglobins: hemoglobin Alabama (beta 39 (C5) gln-to-lys) and hemoglobin Montgomery (alpha 48 (CD6) leu-to-arg). Biochim. Biophys. Acta 379: 28-32, 1975. [PubMed: 1115799, related citations]

  168. Brittenham, G., Lozoff, B., Harris, J. W., Nayudu, N. V. S., Gravely, M., Wilson, J. B., Lam, H., Huisman, T. H. J. Hemoglobin Hofu or beta (126 (H4) val-to-glu) found in combination with hemoglobin S. Hemoglobin 2: 541-549, 1978. [PubMed: 750554, related citations] [Full Text]

  169. Bromberg, P. A., Alben, J. O., Bare, G. H., Balcerzak, S. P., Jones, R. T., Brimhall, B., Padilla, F. High oxygen affinity variant of haemoglobin Little Rock with unique properties. Nature N.B. 243: 177-179, 1973. [PubMed: 4514629, related citations] [Full Text]

  170. Brown, W. J., Niazi, G. A., Jayalakshmi, M., Abraham, E. C., Huisman, T. H. J. Hemoglobin Athens-Georgia, or beta40 (C6) arg-to-lys, a hemoglobin variant with an increased oxygen affinity. Biochim. Biophys. Acta 439: 70-76, 1976. [PubMed: 8114, related citations] [Full Text]

  171. Broxson, E. H., Hine, T. K., Moo-Penn, W. F. Hb Muskegon [beta-83 (EF7) gly-to-arg]: a new variant found in a family from the U.S. Hemoglobin 17: 85-86, 1993. [PubMed: 8454474, related citations] [Full Text]

  172. Buckett, L. B., Sharma, V. S., Pisciotta, A. V., Ranney, H., Bruckheimer, P. Hemoglobin Mequon beta 41 (C7) phenylalanine-to-tyrosine. (Abstract) Clin. Res. 22: 176A, 1974.

  173. Budge, L. J., Bradley, T. B., Graham, J. L. Hemoglobin Riyadh in a Mexican American family of Spanish ancestry. Hemoglobin 1: 283-295, 1977. [PubMed: 893129, related citations] [Full Text]

  174. Bundgaard, J. R., Bjerrum, O. W., Tybjaerg-Hansen, A. A new variant with two amino acid substitutions: Hb S-Cameroon [beta-6(A3)glu-to-val; beta-90(F6)glu-to-lys]. Hemoglobin 28: 131-135, 2004. [PubMed: 15182055, related citations] [Full Text]

  175. Bunn, H. F., Altman, A. J., Stangland, K., Firshein, S. I., Forget, B., Schmidt, G. J., Jones, R. T. Hemoglobins Aida (alpha 64 asp-to-asn) and D-Los Angeles (beta 121 glu-to-gln) in an Asian-Indian family. Hemoglobin 2: 531-540, 1978. [PubMed: 750553, related citations] [Full Text]

  176. Bunn, H. F., Bradley, T. B., Davis, W. E., Drysdale, J. W., Burke, J. F., Beck, W. S., Laver, M. B. Structural and functional studies on hemoglobin Bethesda (beta 145 his), a variant associated with compensatory erythrocytosis. J. Clin. Invest. 51: 2299-2309, 1972. [PubMed: 4639015, related citations] [Full Text]

  177. Bunn, H. F., Schmidt, G. J., Haney, D. N., Dluhy, R. G. Hemoglobin Cranston, an unstable variant having an elongated beta chain due to nonhomologous crossover between two normal beta chain genes. Proc. Nat. Acad. Sci. 72: 3609-3613, 1975. [PubMed: 1059149, related citations] [Full Text]

  178. Bursaux, E., Blouquit, Y., Poyart, C., Rosa, J., Arous, N., Bohn, B. Hemoglobin Ty Gard (beta124 pro-to-gln): a stable high O2 affinity variant at the alpha-1-beta-1 contact. FEBS Lett. 88: 155-159, 1978. [PubMed: 639985, related citations] [Full Text]

  179. Butler, W. M., Spratling, L., Kark, J. A., Schoomaker, E. B. Hemoglobin Osler: report of a family with exercise studies before and after phlebotomy. Am. J. Hemat. 13: 293-301, 1982. [PubMed: 7158624, related citations] [Full Text]

  180. Cai, S. P., Chang, C. A., Zhang, J. Z., Saiki, R. K., Erlich, H. A., Kan, Y. W. Rapid prenatal diagnosis of beta-thalassemia using DNA amplification and nonradioactive probes. Blood 73: 372-374, 1989. [PubMed: 2917180, related citations]

  181. Cai, S.-P., Kan, Y. W. Identification of the multiple beta-thalassemia mutations by denaturing gradient gel electrophoresis. J. Clin. Invest. 85: 550-553, 1990. [PubMed: 2298920, related citations] [Full Text]

  182. Cai, S.-P., Zhang, J.-Z., Doherty, M., Kan, Y. W. A new TATA box mutation detected at prenatal diagnosis for beta-thalassemia. Am. J. Hum. Genet. 45: 112-114, 1989. [PubMed: 2741940, related citations]

  183. Cai Yin Lin, Wang He Be, Yang Xue Yong, Liu Zheng Hong, Ao Zhong Fang, Gong Dao Hua, Ma Jian Ping, Wang Min Juan, Ma Da Rong, Xu Yu Qing, Chen En Hui. A new fast-moving hemoglobin variant, Hb J Luhe beta8 (A5) lys-to-glutamine. Chinese Hemat. J. 3: 263-265, 1982.

  184. Camaschella, C., Bertero, M. T., Serra, A., Dall'Acqua, M., Gasparini, P., Trento, M., Vettore, L., Perona, G., Saglio, G., Mazza, U. A benign form of thalassaemia intermedia may be determined by the interaction of triplicated alpha locus and heterozygous beta-thalassaemia. Brit. J. Haemat. 66: 103-107, 1987. [PubMed: 3593644, related citations] [Full Text]

  185. Camaschella, C., Serra, A., Gottardi, E., Alfarano, A., Revello, D., Mazza, U., Saglio, G. A new hereditary persistence of fetal hemoglobin deletion has the breakpoint within the 3-prime beta-globin gene enhancer. Blood 75: 1000-1005, 1990. [PubMed: 1689188, related citations]

  186. Camaschella, C., Serra, A., Saglio, G., Bertero, M. T., Mazza, U., Terzoli, S., Brambati, B., Cremonesi, L., Travis, M., Ferrari, M. Meiotic recombination in the beta-globin gene cluster causing an error in prenatal diagnosis of beta-thalassaemia. J. Med. Genet. 25: 307-310, 1988. [PubMed: 2898535, related citations] [Full Text]

  187. Cao, A., Furbetta, M., Galanello, R., Melis, M. A., Angius, A., Ximenes, A., Rosatelli, C., Ruggeri, R., Addis, M., Tuveri, T., Falchi, A. M., Paglietti, E., Scalas, M. T. Prevention of homozygous beta-thalassemia by carrier screening and prenatal diagnosis in Sardinia. Am. J. Hum. Genet. 33: 592-605, 1981. [PubMed: 7258188, related citations]

  188. Carbone, V., Salzano, A. M., Pagano, L., Buffardi, S., De Rosa, C., Pucci, P. Identification of Hb Villejuif (beta-123(H1)thr-to-ile) in Southern Italy. Hemoglobin 25: 67-78, 2001. [PubMed: 11300351, related citations] [Full Text]

  189. Carbone, V., Salzano, A. M., Pagano, L., Viola, A., Buffardi, S., De Rosa, C., Pucci, P. Hb Rainier [beta-145(HC2)tyr to cys] in Italy. Characterization of the amino acid substitution and the DNA mutation. Hemoglobin 23: 111-124, 1999. [PubMed: 10335979, related citations] [Full Text]

  190. Carcassi, U. E. F., Pintus, A., Gravely, M. E., Huisman, T. H. J. Beta-zero-thalassemia in association with Hb Leslie (beta 131GLN to 0) in a Sardinian family. Hemoglobin 4: 195-200, 1980. [PubMed: 7390864, related citations]

  191. Carrell, R. W., Lehmann, H., Hutchison, H. E. Haemoglobin Koln (beta-98 valine to methionine): an unstable protein causing inclusion body anaemia. Nature 210: 915-917, 1966. [PubMed: 5960324, related citations] [Full Text]

  192. Carrell, R. W., Lehmann, H., Lorkin, P. A., Raik, E., Hunter, E. Haemoglobin Sydney: beta 67 (E 11) valine to alanine: an emerging pattern of unstable haemoglobins. Nature 215: 626-628, 1967. [PubMed: 6050213, related citations] [Full Text]

  193. Carrell, R. W. Personal Communication. Christchurch, New Zealand 1970.

  194. Carver, M. F. H., Kutlar, A. International Hemoglobin Information Center: variant list. Hemoglobin 19: 37-149, 1995. [PubMed: 7615401, related citations]

  195. Casey, R., Kynoch, P. A., Lang, A., Lehmann, H., Nozari, G., Shinton, N. K. Double heterozygosity for two unstable haemoglobins: Hb Sydney (beta67(E11) val-to-ala) and Hb Coventry (beta141(H19) leu deleted). Brit. J. Haemat. 38: 195-209, 1978. [PubMed: 638069, related citations] [Full Text]

  196. Casey, R., Lang, A., Lehmann, H., Shinton, N. K. Double heterozygosity for two unstable hemoglobins: Hb Sydney (beta-67 (E11) val-to-ala) and Hb Coventry (beta-141 (H19) leu deleted). Brit. J. Haemat. 33: 143-144, 1976.

  197. Castagnola, M., Cassiano, L., Rossetti, D. V., Marucci, L., Ferro, A., Scarano, C., Monaco, M., Celozzi, A. M. Hb K-Ibadan [beta46(CD5)gly-to-glu] in an Italian family. Hemoglobin 14: 647-651, 1990. [PubMed: 1983219, related citations]

  198. Cathie, I. A. B. Apparent idiopathic Heinz body anaemia. Great Ormond Street J. 2: 43-48, 1952.

  199. Cepreganova, B., Wilson, J. B., Huisman, T. H. J., Hume, H. A. Hb Nottingham or beta98(FG5)val-to-gly observed as a de novo mutation in a Canadian child. Hemoglobin 16: 77-79, 1992. [PubMed: 1634365, related citations] [Full Text]

  200. Chaganti, R. S. K., Jhanwar, S. C., Antonarakis, S. E., Hayward, W. S. Germ-line chromosomal localization of genes in chromosome 11p linkage: parathyroid hormone, beta-globin, c-Ha-ras-1, and insulin. Somat. Cell Molec. Genet. 11: 197-202, 1985. [PubMed: 3885418, related citations] [Full Text]

  201. Chakravarti, A., Buetow, K. H., Antonarakis, S. E., Waber, P. G., Boehm, C. D., Kazazian, H. H. Nonuniform recombination within the human beta-globin gene cluster. Am. J. Hum. Genet. 36: 1239-1258, 1984. [PubMed: 6097112, related citations]

  202. Chan, V., Chan, T. K., Kan, Y. W., Todd, D. A novel beta-thalassemia frameshift mutation (codon 14/15) detectable by direct visualization of abnormal restriction fragment in amplified genomic DNA. Blood 72: 1420-1423, 1988. [PubMed: 2901867, related citations]

  203. Chang, J. C., Alberti, A., Kan, Y. W. A beta-thalassemia lesion abolishes the same MstII site as the sickle mutation. Nucleic Acids Res. 11: 7789-7794, 1983. [PubMed: 6316272, related citations] [Full Text]

  204. Chang, J. C., Kan, Y. W. Beta-0-thalassemia, a nonsense mutation in man. Proc. Nat. Acad. Sci. 76: 2886-2889, 1979. [PubMed: 88735, related citations] [Full Text]

  205. Chang, J. C., Kan, Y. W. Antenatal diagnosis of sickle cell anaemia by direct analysis of the sickle mutation. Lancet 318: 1127-1129, 1981. Note: Originally Volume II. [PubMed: 6118575, related citations] [Full Text]

  206. Chang, J. C., Kan, Y. W. A sensitive new prenatal test for sickle-cell anemia. New Eng. J. Med. 307: 30-32, 1982. [PubMed: 6176866, related citations] [Full Text]

  207. Chang, J. C., Kan, Y. W. A sensitive test for prenatal diagnosis of sickle cell anemia: direct analysis of amniocyte DNA with MstII. Trans. Assoc. Am. Phys. 95: 71-78, 1982. [PubMed: 6304979, related citations]

  208. Chang, J. C., Temple, G. F., Trecartin, R. F., Kan, Y. W. Beta-zero thalassemia: a nonsense mutation in man, and its correction in vitro. (Abstract) Clin. Res. 27: 457A, 1979.

  209. Chang, J.-G., Lee, L.-S., Chen, P.-H., Chen, Y.-H. Hb Kaohsiung or New York: a T-to-A substitution at codon 113 of the beta-globin chain creates an Alu I cutting site. Hemoglobin 16: 123-125, 1992. [PubMed: 1634358, related citations] [Full Text]

  210. Chang, J.-G., Yang, T.-Y., Perng, L.-I., Wang, J.-C., Tsan, K.-W. Hb Koln [beta-98(FG5)val to met]: the first case found in a Chinese family. Hemoglobin 22: 535-536, 1998. [PubMed: 9859938, related citations] [Full Text]

  211. Chang, J.-G., Yang, T.-Y., Perng, L.-I., Wang, N. M., Peng, C.-T., Tsai, C.-H. Hb Siriraj: a G-to-A substitution at codon 7 of the beta-globin chain creates an MboII cutting site. Hemoglobin 23: 197-199, 1999. [PubMed: 10335989, related citations] [Full Text]

  212. Charache, S., Achuff, S., Winslow, R., Kazazian, H. Oxygen transport in a woman with hemoglobin Hope/beta-plus-thalassemia. J. Lab. Clin. Med. 93: 316-320, 1979. [PubMed: 429843, related citations]

  213. Charache, S., Brimhall, B., Jones, R. T. Polycythemia produced by hemoglobin Osler (beta 145 (HC2) tyr-to-asp). Johns Hopkins Med. J. 136: 132-136, 1975. [PubMed: 1117598, related citations]

  214. Charache, S., Brimhall, B., Milner, P., Cobb, L. Hemoglobin Okaloosa (beta 48 (CD7) leucine to arginine) an unstable variant with low oxygen affinity. J. Clin. Invest. 52: 2858-2864, 1973. [PubMed: 4748512, related citations] [Full Text]

  215. Charache, S., Fox, J., McCurdy, P., Kazazian, H., Jr., Winslow, R. Post-synthetic deamidation of hemoglobin Providence (beta 82 lys-to-asn, asp) and its effect on oxygen transport. J. Clin. Invest. 59: 652-658, 1977. [PubMed: 14973, related citations] [Full Text]

  216. Charache, S., Jacobson, R., Brimhall, B., Murphy, E. A., Hathaway, P., Winslow, R., Jones, R., Rath, C. Hb Potomac (beta 101 glu-to-asp): speculations on placental oxygen transport in carriers of high-affinity hemoglobins. Blood 51: 331-338, 1978. [PubMed: 563749, related citations]

  217. Charache, S., Zinkham, W. H., Dickerman, J. D., Brimhall, B., Dover, G. J. Hemoglobin SC, SS-G(Philadelphia) and SO(Arab) diseases: diagnostic importance of an integrative analysis of clinical, hematologic and electrophoretic findings. Am. J. Med. 62: 439-446, 1977. [PubMed: 842562, related citations] [Full Text]

  218. Chebloune, Y., Pagnier, J., Trabuchet, G., Faure, C., Verdier, G., Labie, D., Nigon, V. Structural analysis of the 5-prime flanking region of the beta-globin gene in African sickle cell anemia patients: further evidence for three origins of the sickle cell mutation in Africa. Proc. Nat. Acad. Sci. 85: 4431-4435, 1988. [PubMed: 2898142, related citations] [Full Text]

  219. Chehab, F. F., Honig, G. R., Kan, Y. W. Spontaneous mutation in beta-thalassaemia producing the same nucleotide substitution as that in a common hereditary form. Lancet 327: 3-5, 1986. Note: Originally Volume I. [PubMed: 2867271, related citations] [Full Text]

  220. Chehab, F. F., Winterhalter, K. H., Kan, Y. W. Characterization of a spontaneous mutation in beta-thalassemia associated with advanced paternal age. Blood 74: 852-854, 1989. [PubMed: 2665856, related citations]

  221. Chen, S. S., Webber, B. B., Wilson, J. B., Huisman, T. H. J. Hb Gainesville-GA or beta46(CD5)gly-to-arg. Hemoglobin 9: 179-181, 1985. [PubMed: 3839773, related citations] [Full Text]

  222. Chen, S. S., Wilson, J. B., Webber, B. B., Kutlar, A., Huisman, T. H. J. Hb G-Copenhagen or beta47(CD6)asp-to-asn observed in a black newborn. Hemoglobin 9: 405-408, 1985. [PubMed: 4077558, related citations] [Full Text]

  223. Chen-Marotel, J., Braconnier, F., Blouquit, Y., Martin-Caburi, J., Kammerer, J., Rosa, J. Hemoglobin Bougardirey-Mali beta 119 (GH2) gly-to-val, an electrophoretically silent variant migrating in isoelectrofocusing as Hb F. Hemoglobin 3: 253-262, 1979. [PubMed: 500370, related citations] [Full Text]

  224. Cheng, T.-C., Orkin, S. H., Antonarakis, S. E., Potter, M. J., Sexton, J. P., Markham, A. F., Giardina, P. J. V., Li, A., Kazazian, H. H., Jr. Beta-thalassemia in Chinese: use of in vivo RNA analysis and oligonucleotide hybridization in systematic characterization of molecular defects. Proc. Nat. Acad. Sci. 81: 2821-2825, 1984. [PubMed: 6585831, related citations] [Full Text]

  225. Chernoff, A. I., Perillie, P. E. The amino acid composition of hemoglobin B New Haven-2 or HgB N (New Haven). Biochem. Biophys. Res. Commun. 16: 368-372, 1964. [PubMed: 5872025, related citations] [Full Text]

  226. Chernoff, A. I., Pettit, N. M. The amino acid composition of hemoglobin. III. A qualitative method for identifying abnormalities of the polypeptide chains of hemoglobin. Blood 24: 750-756, 1964. [PubMed: 14235356, related citations]

  227. Chernoff, A. I., Weichselbaum, T. E. A microhemolyzing technic for preparing solutions of hemoglobin for paper electrophoretic analysis. Am. J. Clin. Path. 30: 120-125, 1958. [PubMed: 13559175, related citations] [Full Text]

  228. Chiancone, E., Norne, J. E., Bonaventura, J., Bonaventura, C., Forsen, S. Nuclear magnetic resonance quadrupole relaxation study of chloride binding to hemoglobin Abruzzo (beta 143 his-to-arg). Biochim. Biophys. Acta 336: 403-406, 1974.

  229. Chibani, J., Vidaud, M., Duquesnoy, P., Berge-Lefranc, J. L., Pirastu, M., Ellouze, F., Rosa, J., Goossens, M. The peculiar spectrum of beta-thalassemia genes in Tunisia. Hum. Genet. 78: 190-192, 1988. [PubMed: 3422218, related citations] [Full Text]

  230. Chifu, Y., Nakashima, H., Hara, H., Yokota, E., Imamura, T. Beta-thalassemia major resulting from a compound heterozygosity for the beta-globin gene mutation: further evidence for multiple origin and migration of the thalassemia gene. Hum. Genet. 89: 343-346, 1992. [PubMed: 1351038, related citations] [Full Text]

  231. Chiu, R. W. K., Lau, T. K., Leung, T. N., Chow, K. C. K., Chui, D. H. K., Lo, Y. M. D. Prenatal exclusion of beta thalassaemia major by examination of maternal plasma. Lancet 360: 998-1000, 2002. [PubMed: 12383672, related citations] [Full Text]

  232. Cholera, R., Brittain, N. J., Gillrie, M. R., Lopera-Mesa, T. M., Diakite, S. A. S., Arie, T., Krause, M. A., Guindo, A., Tubman, A., Fujioka, H., Diallo, D. A., Doumbo, O. K., Ho, M., Wellems, T. E., Fairhurst, R. M. Impaired cytoadherence of Plasmodium falciparum-infected erythrocytes containing sickle hemoglobin. Proc. Nat. Acad. Sci. 105: 991-996, 2008. [PubMed: 18192399, images, related citations] [Full Text]

  233. Chotivanich, K., Udomsangpetch, R., Pattanapanyasat, K., Chierakul, W., Simpson, J., Looareesuwan, S., White, N. Hemoglobin E: a balanced polymorphism protective against high parasitemias and thus severe P falciparum malaria. Blood 100: 1172-1176, 2002. [PubMed: 12149194, related citations]

  234. Chow, E. Y., Haley, L. P., Krikler, S. H., Wadsworth, L. D. Hb Seattle [beta-70(E14)ala-to-asp]: a report of a second kindred in a Ukrainian family. Hemoglobin 18: 231-234, 1994. [PubMed: 7928380, related citations] [Full Text]

  235. Christopoulou, G., Tserga, A., Patrinos, G. P., Papadakis, M. N. Molecular characterization and diagnosis of Hb Crete [beta-129(H7)ala-to-pro]. Hemoglobin 28: 339-342, 2004. [PubMed: 15658190, related citations] [Full Text]

  236. Church, G. M., Gilbert, W. Genomic sequencing. Proc. Nat. Acad. Sci. 81: 1991-1995, 1984. [PubMed: 6326095, related citations] [Full Text]

  237. Ciavatta, D. J., Ryan, T. M., Farmer, S. C., Townes, T. M. Mouse model of human beta-0-thalassemia: targeted deletion of the mouse beta(maj)- and beta(min)-globin genes in embryonic stem cells. Proc. Nat. Acad. Sci. 92: 9259-9263, 1995. [PubMed: 7568113, related citations] [Full Text]

  238. Cin, S., Akar, N., Cavdar, A. O., Arcasoy, A., Dedeoglu, S., Webber, B., Lam, H., Huisman, T. H. J. Hb Summer Hill or beta52(D3)asp-to-his in a Turkish family from Cyprus. Hemoglobin 7: 467-470, 1983. [PubMed: 6629828, related citations] [Full Text]

  239. Clegg, J. B., Naughton, M. A., Weatherall, D. J. An improved method for the characterization of human haemoglobin mutants: identification of alpha-2, beta-2 (95 glu), haemoglobin N (Baltimore). Nature 207: 945-947, 1965. [PubMed: 5886928, related citations] [Full Text]

  240. Clegg, J. B., Naughton, M. A., Weatherall, D. J. Abnormal human haemoglobins. Separation and characterization of the alpha and beta chains by chromatography, and the determination of two new variants, Hb Chesapeake and Hb J(Bangkok). J. Molec. Biol. 19: 91-108, 1966. [PubMed: 5967288, related citations] [Full Text]

  241. Clegg, J. B., Weatherall, D. J., Boon, W. H., Mustafa, D. Two new haemoglobin variants involving proline substitutions. Nature 222: 379-380, 1969. [PubMed: 5782115, related citations] [Full Text]

  242. Cobian, J. G., Magana, M.-T., Perea, F. J., Ibarra, B. Hb Colima (beta-49(CD8)ser-to-cys): a new hemoglobin variant. Hemoglobin 26: 393-395, 2002. [PubMed: 12484635, related citations] [Full Text]

  243. Cohen-Solal, M., Blouquit, Y., Garel, M. C., Gaillard, L., Creyssel, R., Gibaud, A., Rosa, J. Haemoglobin Lyon (beta 17-18 lys-val 0): determination by sequenator analysis. Biochim. Biophys. Acta 351: 306-316, 1974. [PubMed: 4407311, related citations]

  244. Cohen-Solal, M., Lebeau, M., Rosa, J. 'In vitro' normal biosynthesis of an unstable ferri-hemoglobin: hemoglobin Saint Louis B10 (beta 28) leu-to-gln. Nouv. Rev. Franc. Hemat. 14: 621-626, 1974. [PubMed: 4281476, related citations]

  245. Colah, R., Wadia, M., Surve, R., Nadkarni, A., Phanasgaonkar, S., Gorakshakar, A., Mohanty, D., Prome, D., Wajcman, H. Hb D-Agri [beta-9(A6)ser-tyr;beta-121(GH4)glu-gln]: a new Indian hemoglobin variant with two amino acid substitutions in the same beta chain. Hemoglobin 25: 317-321, 2001. [PubMed: 11570725, related citations] [Full Text]

  246. Cole-Strauss, A., Yoon, K., Xiang, Y., Byrne, B. C., Rice, M. C., Gryn, J., Holloman, W. K., Kmiec, E. B. Correction of the mutation responsible for sickle cell anemia by an RNA-DNA oligonucleotide. Science 273: 1386-1388, 1996. [PubMed: 8703073, related citations] [Full Text]

  247. Coleman, M. B., Adams, J. G., Smith, C. M., Steinberg, M. H. Modulation of Hb Koln disease by an additional mutation: Hb Medicine Lake. (Abstract) Blood 82 (suppl. 1): 222a, 1993.

  248. Coleman, M. B., Lu, Z.-H., Smith, C. M., II, Adams, J. G., III, Harrell, A., Plonczynski, M., Steinberg, M. H. Two missense mutations in the beta-globin gene can cause severe beta thalassemia: hemoglobin Medicine Lake (beta-32[B14]leu-to-glu; 98[FG5]val-to-met). J. Clin. Invest. 95: 503-509, 1995. [PubMed: 7860732, related citations] [Full Text]

  249. Coleman, M. B., Steinberg, M. H., Adams, J. G., III. Hemoglobin Terre Haute arginine beta-106: a posthumous correction to the original structure of hemoglobin Indianapolis. J. Biol. Chem. 266: 5798-5800, 1991. [PubMed: 2005117, related citations]

  250. Coleman, M. D., Adams, J. G., Steinberg, M. H. A possible somatic mutation of the human beta-globin gene. (Abstract) Blood 72 (suppl. 1): 58a, 1988.

  251. Collins, F. S., Cole, J. L., Lockwood, W. K., Iannuzzi, M. C. The deletion in both common types of hereditary persistence of fetal hemoglobin is approximately 105 kilobases. Blood 70: 1797-1803, 1987. [PubMed: 2445400, related citations]

  252. Como, P. F., Hocking, D., Trent, R. A., Wilkinson, T., Wylie, B. R., Bruce, D., Kronenberg, H. Hb Geelong (beta139 asn-to-asp) and Hb Stanmore (beta111 val-to-ala): two new unstable haemoglobins which illustrate the problem of distinguishing a haemoglobin with a thalassaemic phenotype from one inherited along with beta thalassaemia in either cis or trans. (Abstract) Proceedings of the Haematology Society, Australia, Perth, West Australia, October 1984.

  253. Como, P. F., Kennett, D., Wilkinson, T., Kronenberg, H. A new hemoglobin with high oxygen affinity--hemoglobin Bunbury: beta(94 (FG1) asp-to-asn). Hemoglobin 7: 413-421, 1983. [PubMed: 6629823, related citations] [Full Text]

  254. Converse, J., Sharma, V., Reiss-Rosenberg, G., Ranney, H. M., Danish, E., Bowman, L. S., Harris, J. W. Some properties of hemoglobin Mobile (beta73 asp-to-val). Hemoglobin 9: 33-45, 1985. [PubMed: 3997539, related citations] [Full Text]

  255. Corso, D., Cognata, B., Ciaccio, C., Piazza, T., Dibenedetto, S. P., Samperi, P., Russo Mancuso, G., Schiliro, G. Hb Agenogi (beta90(F6)glu-to-lys) and beta-0-thalassemia in a Sicilian family. Hemoglobin 14: 549-553, 1990. [PubMed: 2079434, related citations] [Full Text]

  256. Costa, J.-M., Benachi, A., Gautier, E. New strategy for prenatal diagnosis of X-linked disorders. (Letter) New Eng. J. Med. 346: 1502 only, 2002. [PubMed: 12000828, related citations] [Full Text]

  257. Cotton, F., Hansen, V., Lin, C., Parma, J., Cochaux, P., Damis, E., Vertongen, F., Gulbis, B. Hb Ube-2 (alpha-68(E17)asn-to-asp) and Hb Hafnia (beta-116(G18)his-to-gln) observed during neonatal screening in Brussels. Hemoglobin 24: 65-69, 2000. [PubMed: 10722118, related citations] [Full Text]

  258. Cotton, R. G. H., Rodrigues, N. R., Campbell, R. D. Reactivity of cytosine and thymine in single-base-pair mismatches with hydroxylamine and osmium tetroxide and its application to the study of mutations. Proc. Nat. Acad. Sci. 85: 4397-4401, 1988. [PubMed: 3260032, related citations] [Full Text]

  259. Currat, M., Trabuchet, G., Rees, D., Perrin, P., Harding, R. M., Clegg, J. B., Langaney, A., Excoffier, L. Molecular analysis of the beta-globin gene cluster in the Niokholo Mandenka population reveals a recent origin of the beta-S Senegal mutation. Am. J. Hum. Genet. 70: 207-223, 2002. [PubMed: 11741197, images, related citations] [Full Text]

  260. Curtin, P., Pirastu, M., Kan, Y. W., Gobert-Jones, J. A., Stephens, A. D., Lehmann, H. A distant gene deletion affects beta-globin gene function in an atypical gamma-delta-beta-thalassemia. J. Clin. Invest. 76: 1554-1558, 1985. [PubMed: 2997283, related citations] [Full Text]

  261. Curtin, P. T., Liu, D., Liu, W., Chang, J. C., Kan, Y. W. Human beta-globin gene expression in transgenic mice is enhanced by a distant DNase I hypersensitive site. Proc. Nat. Acad. Sci. 86: 7082-7086, 1989. [PubMed: 2780563, related citations] [Full Text]

  262. Curuk, M. A., Howard, S. C., Kutlar, A., Huisman, T. H. J. A newly discovered beta-zero-thalassemia (IVS-II-850, G-to-A) mutation in a North European family. Hemoglobin 19: 207-211, 1995. [PubMed: 7558878, related citations] [Full Text]

  263. Cyrklaff, M., Sanchez, C. P., Kilian, N., Bisseye, C., Simpore, J., Frischknecht, F., Lanzer, M. Hemoglobins S and C interfere with actin remodeling in Plasmodium falciparum-infected erythrocytes. Science 334: 1283-1286, 2011. [PubMed: 22075726, related citations] [Full Text]

  264. Dacie, J. V., Shinton, N. K., Gaffney, P. J., Jr., Carrell, R. W., Lehmann, H. Haemoglobin Hammersmith (beta 42 (CD 1) phe to ser). Nature 216: 663-665, 1967. [PubMed: 6082463, related citations] [Full Text]

  265. Danish, E. H., Harris, J. W., Ahmed, F., Anderson, H. Hb Rothschild (beta 37 (C3) trp-to-arg): clinical studies. Hemoglobin 6: 51-55, 1982. [PubMed: 7068435, related citations] [Full Text]

  266. Dash, S., Das, R. Late emergence of polycythemia in a case of Hb Chandigarh [beta-94(FG1)asp-to-gly]. Hemoglobin 28: 273-274, 2004. [PubMed: 15481898, related citations] [Full Text]

  267. Dash, S., Wilson, J. B., Webber, B. B., Kutlar, A., Huisman, T. H. J. Hb Chandigarh or beta94(FG1)asp-to-gly observed in an Indian family. Hemoglobin 13: 749-752, 1989. [PubMed: 2634672, related citations] [Full Text]

  268. De Angioletti, M., Di Girgenti, C., Messineo, R., Capra, M., Carestia, C. Hb A2-Monreale (delta-146 (HC3) his-to-arg), a novel delta chain variant detected in west Sicily. Hemoglobin 26: 1-5, 2002. [PubMed: 11939506, related citations] [Full Text]

  269. De Angioletti, M., Maglione, G., Ferranti, P., de Bonis, C., Lacerra, G., Scarallo, A., Pagano, L., Fioretti, G., Cutolo, R., Malorni, A., Pucci, P., Carestia, C. Hb City of Hope [beta69(E13)gly-to-ser] in Italy: association of the gene with haplotype IX. Hemoglobin 16: 27-34, 1992. [PubMed: 1353069, related citations] [Full Text]

  270. De Biasi, R., Spiteri, D., Caldora, M., Iodice, R., Pucci, P., Malorni, A., Ferranti, P., Marino, G. Identification by fast atom bombardment mass spectrometry of Hb Indianapolis (beta112 (G14) cys-to-arg) in a family from Naples, Italy. Hemoglobin 12: 323-336, 1988. [PubMed: 3170235, related citations] [Full Text]

  271. de Castro, C. M., Devlin, B., Fleenor, D. E., Lee, M. E., Kaufman, R. E. A novel beta-globin mutation, beta-Durham-NC (beta-114-leu-pro), produces a dominant thalassemia-like phenotype. Blood 83: 1109-1116, 1994. [PubMed: 8111050, related citations]

  272. De Jong, W. W. W., Went, L. N., Bernini, L. F. Abnormal haemoglobin--chemical characterization of hemoglobin Leiden. Nature 220: 788-789, 1968. [PubMed: 5698750, related citations] [Full Text]

  273. de Pablos, J. M., Kutlar, A., Wilson, J. B., Webber, B. B., Hu, H., Huisman, T. H. J. Hb D-Granada or beta22 (B4) glu-to-val. Hemoglobin 11: 563-565, 1987. [PubMed: 3446652, related citations] [Full Text]

  274. de Weinstein, B. I., Plaseska-Karanfilska, D., Efremov, G. D. Hb Saint Etienne or Hb Istanbul (beta-92(F8)his-to-gln) found in an Argentinean family. Hemoglobin 24: 149-152, 2000. [PubMed: 10870887, related citations] [Full Text]

  275. Deacon-Smith, R. A., Lee-Potter, J. P. An unstable haemoglobin, Hb Tacoma beta 30 (B12) arg-to-ser, detected at birth by the demonstration of red cell inclusions. J. Clin. Path. 31: 883-887, 1978. [PubMed: 711920, related citations] [Full Text]

  276. deCastro, C. M., Lee, M., Fleenor, D. E., Devlin, B., Kaufman, R. E. A novel beta-globin mutation, beta-Durham-N.C. [beta(114) leu-to-pro], detected by SSCP, produces a dominant thalassemia-like phenotype. (Abstract) Blood 80: 6a, 1992.

  277. Deidda, G., Novelletto, A., Hafez, M., Al-Tonbary, Y., Felicetti, L., Terrenato, L., Colombo, B. A new beta-thalassemia produced by a single nucleotide substitution in the conserved dinucleotide sequence of the IVS-I consensus acceptor site (AG-to-AA). Hemoglobin 14: 431-440, 1990. [PubMed: 2283297, related citations] [Full Text]

  278. Deisseroth, A., Nienhuis, A. W., Lawrence, J., Giles, R. E., Turner, P., Ruddle, F. H. Chromosomal localization of the human beta globin gene to human chromosome 11 in somatic cell hybrids. Proc. Nat. Acad. Sci. 75: 1456-1460, 1978. [PubMed: 274732, related citations] [Full Text]

  279. Delanoe, J., North, M. L., Arous, N., Bardakjian, J., Pflumio, F., Brunagel, M. L., Lacombe, C., Poyart, C., Galacteros, F., Rosa, J., Blouquit, Y. Hb Saverne: a new variant having an elongated beta chain. (Abstract) Blood 64: 56a, 1984. Note: Abstract: Hemoglobin 9: 108 only, 1985.

  280. Delanoe-Garin, J., Arous, N., Blouquit, Y., Hafsia, R., Bardakdjian, J., Lacombe, C., Rosa, J., Galacteros, F. Hemoglobin Kenitra beta69 (E13) gly-to-arg: a new beta variant of elevated expression associated with alpha-thalassemia, found in a Moroccan woman. Hemoglobin 9: 1-9, 1985. [PubMed: 3838975, related citations] [Full Text]

  281. Delanoe-Garin, J., Rhoda, M. D., Craescu, C. T., Bardakjian, J., Blouquit, Y., Lacombe, C., Arous, N., Poyart, C., Ganeval, D., Girot, R., Riou, J., Galacteros, F. Hemoglobin J Iran beta77 (EF1) his-to-asp in a Russian-Armenian family. Hemoglobin 10: 365-378, 1986. [PubMed: 2943700, related citations] [Full Text]

  282. Deutsch, S., Darbellay, R., Offord, R., Frutiger, A., Kister, J., Wajcman, H., Beris, P. Hb Iraq-Halabja beta-10(A7)ala-to-val(GCC-to-GTC): a new beta-chain silent variant in a family with multiple Hb disorders. Am. J. Hemat. 61: 187-193, 1999. [PubMed: 10398311, related citations] [Full Text]

  283. Devaraj, R., Wilson, J. B., Huisman, T. H. J. Hb Regina or beta96(FG3)leu-to-val: a high oxygen affinity variant discovered by cation-exchange HPLC. Am. J. Hemat. 19: 195-200, 1985. [PubMed: 3839106, related citations] [Full Text]

  284. Dherte, P., Lehmann, H., Vandepitte, J. Haemoglobin P in a family in the Belgian Congo. Nature 184: 1133-1135, 1959. [PubMed: 13816360, related citations] [Full Text]

  285. Di Iorio, E. E., Winterhalter, K. H., Wilson, K., Rosenmund, A., Marti, H. R. Swiss family with hemoglobin P Galveston (beta-117 his-to-arg) including 2 patients with Hb P-beta thalassemia. Blut 31: 61-68, 1975. [PubMed: 1164567, related citations] [Full Text]

  286. Di Marzo, R., Dowling, C. E., Wong, C., Maggio, A., Kazazian, H. H., Jr. The spectrum of beta-thalassemia mutations in Sicily. Brit. J. Haemat. 69: 393-397, 1988. [PubMed: 3408672, related citations] [Full Text]

  287. Dianzani, I., Ramus, S., Cotton, R. G. H., Camaschella, C. A spontaneous mutation causing unstable Hb Hammersmith: detection of the beta42 TTT-to-TCT change by CCM and direct sequencing. Brit. J. Haemat. 79: 127-129, 1991. [PubMed: 1911375, related citations] [Full Text]

  288. Diaz-Chico, J. C., Huang, H. J., Juricic, D., Efremov, G. D., Wadsworth, L. D., Huisman, T. H. J. Two new large deletions resulting in epsilon-gamma-delta-beta-thalassemia. Acta Haemat. 80: 79-84, 1988. [PubMed: 3138875, related citations] [Full Text]

  289. Dickerman, J. D., Holtzman, N. A., Zinkham, W. H. Hemoglobin Zurich. A third family presenting hemolytic reactions to sulfonamides. Am. J. Med. 55: 638-642, 1973. [PubMed: 4749206, related citations] [Full Text]

  290. Dincol, G., Dincol, K., Erdem, S. Hb G-Coushatta or beta22 (B4) glu-to-ala in a Turkish male. Hemoglobin 13: 75-77, 1989. [PubMed: 2703366, related citations] [Full Text]

  291. Ding, C., Chiu, R. W. K., Lau, T. K., Leung, T. N., Chan, L. C., Chan, A. Y. Y., Charoenkwan, P., Ng, I. S. L., Law, H., Ma, E. S. K., Xu, X., Wanapirak, C., Sanguansermsri, T., Liao, C., Ai, M. A. T. J., Chui, D. H. K., Cantor, C. R. MS analysis of single-nucleotide differences in circulating nucleic acids: application to noninvasive prenatal diagnosis. Proc. Nat. Acad. Sci. 101: 10762-10767, 2004. [PubMed: 15247415, images, related citations] [Full Text]

  292. Divoky, V., Bisse, E., Wilson, J. B., Gu, L.-H., Wieland, H., Heinrichs, I., Prior, J. F., Huisman, T. H. J. Heterozygosity for the IVS-I-5 (G-to-C) mutation with a G-to-A change at codon 18 (val-to-met; Hb Baden) in cis and a T-to-G mutation at codon 126 (val-to-gly; Hb Dhonburi) in trans resulting in a thalassemia intermedia. Biochim. Biophys. Acta 1180: 173-179, 1992. [PubMed: 1463768, related citations] [Full Text]

  293. Divoky, V., Svobodova, M., Indrak, K., Chrobak, L., Molchanova, T. P., Huisman, T. H. J. Hb Hradec Kralove (Hb HK) or beta-115(G17)ala-to-asp, a severely unstable hemoglobin variant resulting in a dominant beta-thalassemia trait in a Czech family. Hemoglobin 17: 319-328, 1993. [PubMed: 7693620, related citations] [Full Text]

  294. Djoumessi, S., Rousseaux, J., Dautrevaux, M. Structural studies of a new hemoglobin: Hb J Lens, beta13 (A10) ala-to-asp. FEBS Lett. 136: 145-147, 1981. [PubMed: 7319057, related citations] [Full Text]

  295. Dlott, D., Frauenfelder, H., Langer, P., Roder, H., Di Iorio, E. E. Nanosecond flash photolysis study of carbon monoxide binding to the beta chain of hemoglobin Zurich (beta63(E7) his-to-arg). Proc. Nat. Acad. Sci. 80: 6239-6243, 1983. [PubMed: 6578506, related citations] [Full Text]

  296. Dobbs, N. B., Jr., Simmons, J. W., Wilson, J. B., Huisman, T. H. J. Hemoglobin Jenkins or hemoglobin-N Baltimore or beta glu 95. Biochim. Biophys. Acta 117: 492-494, 1966. [PubMed: 5961314, related citations] [Full Text]

  297. Dobkin, C., Pergolizzi, R. G., Bahre, P., Bank, A. Abnormal splice in a mutant human beta-globin gene not at the site of a mutation. Proc. Nat. Acad. Sci. 80: 1184-1188, 1983. [PubMed: 6298782, related citations] [Full Text]

  298. Driscoll, M. C., Baird, M., Bank, A., Rachmilewitz, E. A. A new polymorphism in the human beta-globin gene useful in antenatal diagnosis. J. Clin. Invest. 68: 915-919, 1981. [PubMed: 6270195, related citations] [Full Text]

  299. Driscoll, M. C., Dobkin, C. S., Alter, B. P. Gamma-delta-beta-thalassemia due to a de novo mutation deleting the 5-prime beta-globin gene activation-region hypersensitive sites. Proc. Nat. Acad. Sci. 86: 7470-7474, 1989. [PubMed: 2798417, related citations] [Full Text]

  300. Duwig, I., North, M. L., Barth, J. G., Rieffel, M., Nierengarten, P., Arous, N., Riou, J., Galacteros, F. Aspects hematologiques et anomalies structurales d'une nouvelle hemoglobine instable: l'Hb Sarrebourg beta(131) (H9) gln-to-arg. (Abstract) Nouv. Rev. Franc. Hemat. 29: 344, 1987.

  301. Dye, M. J., Proudfoot, N. J. Multiple transcript cleavage precedes polymerase release in transcription by RNA polymerase II. Cell 105: 669-681, 2001. [PubMed: 11389836, related citations] [Full Text]

  302. Economou, E. P., Antonarakis, S. E., Dowling, C. E., Ibarra, B., de la Nova, E., Kazazian, H. H., Jr. Molecular characterization of beta-thalassemia in Mexicans. (Abstract) Clin. Res. 38: 387A, 1990.

  303. Edgar, R. S. Conditional lethals. In: Cairns, J.; Stent, G. S.; Watson, J. D.: Phage and the Origins of Molecular Biology. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory (pub.) 1966. Pp. 166-170.

  304. Edington, G. M., Lehmann, H., Schneider, R. G. Characterization and genetics of haemoglobin G. Nature 175: 850-851, 1955. [PubMed: 14370233, related citations] [Full Text]

  305. Edison, E. S., Shaji, R. V., Devi, S. G., Kumar, S. S., Srivastava, A., Chandy, M. Hb Showa-Yakushiji (beta-110(G12)leu-to-pro) in four unrelated patients from West Bengal. Hemoglobin 29: 19-25, 2005. [PubMed: 15768552, related citations]

  306. Edison, E. S., Shaji, R. V., Srivastava, A., Chandy, M. Hyperbilirubinemia in homozygous HbE disease is associated with the UGT1A1 gene polymorphism. Hemoglobin 29: 189-195, 2005. [PubMed: 16114182, related citations] [Full Text]

  307. Efremov, G. D., Duma, H., Rudivic, R., Rolovic, Z., Wilson, J. B., Huisman, T. H. J. Hemoglobin Beograd or beta 121 glu-to-val (GH4). Biochim. Biophys. Acta 328: 81-83, 1973. [PubMed: 4761994, related citations] [Full Text]

  308. Efremov, G. D., Huisman, T. H. J., Smith, L. L., Wilson, J. B., Kitchens, J. L., Wrightstone, R. N., Adams, H. R. Hemoglobin Richmond, a human hemoglobin which forms asymmetric hybrids with other hemoglobins. J. Biol. Chem. 244: 6105-6116, 1969. [PubMed: 4981790, related citations]

  309. Efremov, G. D., Huisman, T. H. J., Stanulovic, M., Zurovec, M., Duma, H., Wilson, J. B., Jeremic, V. Haemoglobin M Saskatoon and Haemoglobin M Hyde Park in two Yugoslavian families. Scand. J. Haemat. 13: 48-60, 1974. [PubMed: 4413625, related citations] [Full Text]

  310. Efremov, G. D., Jankovic, L., Juricic, D., Stojancov, A., Wilson, J. B., Webber, B. B., Kutlar, F., Kutlar, A., Hu, H., Huisman, T. H. J. Hb Bushwick [beta74(E18)gly-to-val] heterozygotes in a Yugoslavian family have 35 to 40% of the unstable variant. Hemoglobin 11: 557-562, 1987. [PubMed: 3446651, related citations]

  311. Efstratiadis, A., Posakony, J. W., Maniatis, T., Lawn, R. M., O'Connell, C., Spritz, R. A., DeRiel, J. K., Forget, B. G., Weissman, S. M., Slightom, J. L., Blechl, A. E., Smithies, O., Baralle, F. E., Shoulders, C. C., Proudfoot, N. J. The structure and evolution of the human beta-globin gene family. Cell 21: 653-668, 1980. [PubMed: 6985477, related citations] [Full Text]

  312. Eigel, A., Schnee, J., Oehme, R., Horst, J. Mutation analysis of beta-thalassemia genes in a German family reveals a rare transversion in the first intron. Hum. Genet. 81: 371-372, 1989. [PubMed: 2703241, related citations] [Full Text]

  313. El-Hazmi, M. A. F., Jabbar, F. A., Al-Swailem, A. R., Warsy, A. S. Beta-globin gene polymorphism in Saudis--triple Hpa I fragments. Hum. Genet. 74: 313-315, 1986. [PubMed: 2877940, related citations] [Full Text]

  314. El-Hazmi, M. A. F., Lehmann, H. Hemoglobin Riyadh--beta 120 (GH3) lys-to-asn: a new variant found in association with alpha-thalassemia and iron deficiency. Hemoglobin 1: 59-74, 1977.

  315. Elder, G. E., Lappin, T. R. J., Horne, A. B., Fairbanks, V. F., Jones, R. T., Winter, P. C., Green, B. N., Hoyer, J. D., Reynolds, T. M., Shih, D. T.-B., McCormick, D. J., Kubik, K. S., Madden, B. J., Head, C. G., Harvey, D., Roberts, N. B. Hemoglobin Old Dominion/Burton-upon-Trent, beta-143 (H21) his-to-tyr, codon 143 CAC-to-TAC--a variant with altered oxygen affinity that compromises measurement of glycated hemoglobin in diabetes mellitus: structure, function, and DNA sequence. Mayo Clin. Proc. 73: 321-328, 1998. [PubMed: 9559035, related citations]

  316. Elion, J., Belkhodja, O., Wajcman, H., Labie, D. Two variants of hemoglobin D in the Algerian population: hemoglobin D Ouled Rabah beta-19 (BI) asn-to-lys and hemoglobin D Iran beta-22 (B4) glu-to-gln. Biochim. Biophys. Acta 310: 360-364, 1973. [PubMed: 4719147, related citations] [Full Text]

  317. Elion, J., Wajcman, H., Belkhodja-Dunda, O., Lapoumeroulie, C., Labie, D., Messerschmitt, J., Staal, A. M., Desablens, B. Hemoglobin J Amiens, beta17 (A14) lys replaced by asn: coincidence of a functionally silent new abnormal hemoglobin and a polycythemia vera. Nouv. Rev. Franc. Hemat. 21: 347-352, 1979. [PubMed: 121938, related citations]

  318. Elwan, S., Baklouti, F., El-Kabsh, M., Abdelrahman, F., Delaunay, J. Hemoglobin Knossos (beta27 (B9) ala-to-ser) in Egypt. Hemoglobin 11: 139-143, 1987. [PubMed: 3114175, related citations] [Full Text]

  319. Embury, S. H., Scharf, S. J., Saiki, R. K., Gholson, M. A., Golbus, M., Arnheim, N., Erlich, H. A. Rapid prenatal diagnosis of sickle cell anemia by a new method of DNA analysis. New Eng. J. Med. 316: 656-661, 1987. [PubMed: 3821796, related citations] [Full Text]

  320. Enoki, Y., Ohga, Y., Furukawa, K., Takaya, A., Sakata, S., Kohzuki, H., Shimizu, S., Tsujii, T. Hb Hope, beta136 (H14) gly-to-asp, in a diabetic Japanese female and its functional characterization. Hemoglobin 13: 17-32, 1989. [PubMed: 2703363, related citations] [Full Text]

  321. Enver, T., Raich, N., Ebens, A. J., Papayannopoulou, T., Costantini, F., Stamatoyannopoulos, G. Developmental regulation of human fetal-to-adult globin gene switching in transgenic mice. Nature 344: 309-313, 1990. [PubMed: 2314472, related citations] [Full Text]

  322. Epner, E., Reik, A., Cimbora, D., Telling, A., Bender, M. A., Fiering, S., Enver, T., Martin, D. I. K., Kennedy, M., Keller, G., Groudine, M. The beta-globin LCR is not necessary for an open chromatin structure of developmentally regulated transcription of the native mouse beta-globin locus. Molec. Cell. 2: 447-455, 1998. [PubMed: 9809066, related citations] [Full Text]

  323. Epstein, R. H., Bolle, A., Steinberg, C. M., Kellenberger, E., Boy de la Tour, E., Chevalley, R., Edgar, R. S., Susman, M., Denhardt, G. H., Lielausis, A. Physiological studies of conditional lethal mutants of bacteriophage T4D. Cold Spring Harbor Symp. Quant. Biol. 28: 375-394, 1963.

  324. Fabritius, H., Cabannes, R., Boissel, J. P., Wacjman, H., Labie, D. Hemoglobin Cocody (beta21(B3)asp-to-asn): hematologic aspects of heterozygosity and of Hb Cocody/beta(+) thalassemia. Hemoglobin 9: 193-196, 1985. [PubMed: 4030382, related citations] [Full Text]

  325. Fabry, M. E., Kaul, D. K., Raventos, C., Baez, S., Rieder, R., Nagel, R. L. Some aspects of the pathophysiology of homozygous Hb CC erythrocytes. J. Clin. Invest. 67: 1284-1291, 1981. [PubMed: 7229029, related citations] [Full Text]

  326. Fairbanks, V. F., Jones, R. T., Head, C., Vogel, S. R., Oliveros, R., Brimhall, B., Silverstein, M. N., Berzins, R. Two families with hemoglobin Sogn, beta-(A11)14 leu-to-arg, in Minnesota and Indiana: hematologic, functional, and biosynthetic features. Mayo Clin. Proc. 65: 793-798, 1990. [PubMed: 2366586, related citations] [Full Text]

  327. Fairbanks, V. F., Maldonado, J. E., Charache, S., Boyer, S. H. Familial erythrocytosis due to electrophoretically undetectable hemoglobin with impaired oxygen dissociation (hemoglobin Malmo, beta 97 gln). Mayo Clin. Proc. 46: 721-727, 1971. [PubMed: 5128393, related citations]

  328. Fairbanks, V. F., Oliveros, R., Brandabur, J. H., Willis, R. R., Fiester, R. F. Homozygous hemoglobin E mimics beta-thalassemia minor without anemia or hemolysis: hematologic, functional, and biosynthetic studies of first North American cases. Am. J. Hemat. 8: 109-121, 1980. [PubMed: 7395858, related citations] [Full Text]

  329. Fairbanks, V. F., Opfell, R. W., Burgert, E. O., Jr. Three families with unstable hemoglobinopathies (Koln, Olmsted and Santa Ana) causing hemolytic anemia with inclusion bodies and pigmenturia. Am. J. Med. 46: 344-359, 1969. [PubMed: 5780360, related citations] [Full Text]

  330. Fairhurst, R. M., Baruch, D. I., Brittain, N. J., Ostera, G. R., Wallach, J. S., Hoang, H. L., Hayton, K., Guindo, A., Makobongo, M. O., Schwartz, O. M., Tounkara, A., Doumbo, O. K., Diallo, D. A., Fujioka, H., Ho, M., Wellems, T. E. Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria. Nature 435: 1117-1121, 2005. [PubMed: 15973412, related citations] [Full Text]

  331. Falcioni, G., Grelloni, F., de Sanctis, G., Pierani, P., Felici, L., Coppa, G. V. Enzymatic antioxidative defence of erythrocytes in an Italian family with Hb Volga or beta27(B9)ala-to-asp. (Letter) Clin. Chim. Acta 178: 345-348, 1988. [PubMed: 3240605, related citations] [Full Text]

  332. Faustino, P., Miranda, A., do Ceu Silva, M., Alves, C., Picanco, I., Ferreira, C., Seixas, M. T., Pina, F., Romao, L. Hb Yaounde [beta-134(H12)val-to-ala] in association with Hb C [beta-6(A3)glu-to-lys] in a Caucasian Portuguese family. Hemoglobin 28: 229-235, 2004. [PubMed: 15481891, related citations] [Full Text]

  333. Faustino, P., Osorio-Almeida, L., Barbot, J., Espirito-Santo, D., Goncalves, J., Romao, L., Martins, M. C., Marques, M. M., Lavinha, J. Novel promoter and splice junction defects add to the genetic, clinical or geographic heterogeneity of beta-thalassaemia in the Portuguese population. Hum. Genet. 89: 573-576, 1992. [PubMed: 1634236, related citations] [Full Text]

  334. Faustino, P., Osorio-Almeida, L., Romao, L., Barbot, J., Fernandes, B., Justica, B., Lavinha, J. Dominantly transmitted beta-thalassemia arising from the production of several aberrant mRNA species and one abnormal peptide. Blood 91: 685-690, 1998. [PubMed: 9427726, related citations]

  335. Fay, K. C., Brennan, S. O., Costello, J. M., Potter, H. C., Williamson, D. A., Trent, R. J., Ockelford, P. A., Boswell, D. R. Haemoglobin Manukau beta-67 [E11] val-to-gly: transfusion-dependent haemolytic anaemia ameliorated by coexisting alpha thalassaemia. Brit. J. Haemat. 85: 352-355, 1993. [PubMed: 8280608, related citations] [Full Text]

  336. Fedorov, A. N., Rasulov, E. M., Bocharova, T. N., Smirnova, E. A., Limborska, S. A. The T-to-A mutation at position -30 of the beta-globin gene found in a Karachai patient with beta-thalassemia intermedia. Hemoglobin 16: 521-523, 1992. [PubMed: 1487424, related citations] [Full Text]

  337. Fei, Y. J., Stoming, T. A., Efremov, G. D., Battacharia, R., Gonzalez-Redondo, J. M., Altay, C., Gurgey, A., Huisman, T. H. J. Beta-thalassemia due to a T-to-A mutation within the ATA box. Biochem. Biophys. Res. Commun. 153: 741-747, 1988. [PubMed: 3382401, related citations] [Full Text]

  338. Fei, Y. J., Stoming, T. A., Kutlar, A., Huisman, T. H. J., Stamatoyannopoulos, G. One form of inclusion body beta-thalassemia is due to a GAA-to-TAA mutation at codon 121 of the beta chain. Blood 73: 1075-1077, 1989. [PubMed: 2563949, related citations]

  339. Felice, A., Abraham, E. C., Miller, A., Stallings, M., Huisman, T. H. J. Is the trimodality of Hb Leslie (beta 131 Gln-to-0) in heterozygotes the result of a variable number of active alpha-chain genes? Evidence for posttranslational control of hemoglobin synthesis. Am. J. Hemat. 5: 1-9, 1978. [PubMed: 747178, related citations] [Full Text]

  340. Feliu-Torres, A., Eberle, S. E., Roldan, A., Gonzalez, S., Sciuccati, G. Hb Johnstown [beta-109(G11)val-to-leu]: a high oxygen affinity variant associated with beta-0-thalassemia. Hemoglobin 28: 335-338, 2004. [PubMed: 15658189, related citations] [Full Text]

  341. Ferreira, A., Marguti, I., Bechmann, I., Jeney, V., Chora, A., Palha, N. R., Rebelo, S., Henri, A., Beuzard, Y., Soares, M. P. Sickle hemoglobin confers tolerance to Plasmodium infection. Cell 145: 398-409, 2011. [PubMed: 21529713, related citations] [Full Text]

  342. Filon, D., Faerman, M., Smith, P., Oppenheim, A. Sequence analysis reveals a beta-thalassemia mutation in the DNA of skeletal remains from the archaeological site of Akhziv, Israel. Nature Genet. 9: 365-368, 1995. [PubMed: 7795641, related citations] [Full Text]

  343. Finney, R., Casey, R., Lehmann, H., Walker, W. Hb Newcastle: beta 92 (F8) his-to-pro. FEBS Lett. 60: 435-438, 1975. [PubMed: 1227988, related citations] [Full Text]

  344. Fischel-Ghodsian, N., Hirsch, P. C., Bohlman, M. C. Rapid detection of the hemoglobin C mutation by allele-specific polymerase chain reaction. (Letter) Am. J. Hum. Genet. 47: 1023-1024, 1990. [PubMed: 2239966, related citations]

  345. Fisher, C., Hanslip, J., Green, B. N., Gupta, V., Old, J. M., Rees, D. C. Hb Watford (beta-1(NA1)val-to-gly): a new, clinically silent hemoglobin variant in linkage with a new neutral mutation (Cap+36(G-A)). Hemoglobin 24: 347-353, 2000. [PubMed: 11186267, related citations] [Full Text]

  346. Flatz, G., Kinderlerer, J. L., Kilmartin, J. V., Lehmann, H. Haemoglobin Tak: a variant with additional residues at the end of the beta-chains. Lancet 297: 732-733, 1971. Note: Originally Volume I. [PubMed: 4101432, related citations] [Full Text]

  347. Flatz, G., Sanguansermsri, T., Sengchanh, S., Horst, D., Horst, J. The 'hot spot' of Hb E [beta-26(B8)glu-to-lys] in Southeast Asia: beta-globin anomalies in the Lao Theung population of Southern Laos. Hemoglobin 28: 197-204, 2004. [PubMed: 15481886, related citations] [Full Text]

  348. Flavell, R. A., Kooter, J. M., De Boer, E. Analysis of the beta-delta-globin gene loci in normal and Hb Lepore DNA: direct determination of gene linkage and intergene distance. Cell 15: 25-41, 1978. [PubMed: 699045, related citations] [Full Text]

  349. Flint, J., Harding, R. M., Clegg, J. B., Boyce, A. J. Why are some genetic diseases common? Distinguishing selection from other processes by molecular analysis of globin gene variants. Hum. Genet. 91: 91-117, 1993. [PubMed: 8462981, related citations] [Full Text]

  350. Forget, B. G. Nucleotide sequence of human beta globin messenger RNA. Hemoglobin 1: 879-881, 1977. [PubMed: 342458, related citations] [Full Text]

  351. Forget, B. G. Molecular genetics of human hemoglobin synthesis. Ann. Intern. Med. 91: 605-616, 1979. [PubMed: 384860, related citations] [Full Text]

  352. Francina, A., Lacombe, C., Baklouti, F., Dorleac, E., Delaunay, J., Souillet, G., Rudigoz, R. C., Arous, N., Rosa, J., Galacteros, F. A new case of Hb Little Rock (beta143(H21)his-to-gln), a high affinity variant: study during pregnancy. Hemoglobin 11: 113-122, 1987. [PubMed: 3623972, related citations] [Full Text]

  353. Frick, P. G., Hitzig, W. H., Betke, K. Hemoglobin Zurich. I. A new hemoglobin anomaly associated with acute hemolytic episodes with inclusion bodies after sulfonamide therapy. Blood 20: 261-271, 1962. [PubMed: 13895148, related citations]

  354. Frischknecht, H., Ventruto, M., Hess, D., Hunziker, P., Rosatelli, M. C., Cao, A., Breitenstein, U., Fehr, J., Tuchschmid, P. Hb Hinwil or beta-38(C4)thr-to-asn: a new beta-chain variant detected in a Swiss family. Hemoglobin 20: 31-40, 1996. [PubMed: 8745430, related citations] [Full Text]

  355. Fritsch, E. F., Lawn, R. M., Maniatis, T. Characterisation of deletions which affect the expression of fetal globin genes in man. Nature 279: 598-603, 1979. [PubMed: 450109, related citations] [Full Text]

  356. Fritsch, E. F., Lawn, R. M., Maniatis, T. Molecular cloning and characterization of the human beta-like globin gene cluster. Cell 19: 959-972, 1980. [PubMed: 6155216, related citations] [Full Text]

  357. Fucharoen, S., Fucharoen, G., Fucharoen, P., Fukumaki, Y. A novel ochre mutation in the beta-thalassemia gene of a Thai: identification by direct cloning of the entire beta-globin gene amplified using polymerase chain reactions. J. Biol. Chem. 264: 7780-7783, 1989. [PubMed: 2542242, related citations]

  358. Fujisawa, K., Yamashiro, K., Hattori, Y., Ohba, Y., Kajita, T., Kageyama, S., Arita, J. Hb Higashitochigi (Hb HT) [beta24 (B6) or beta 25 (B7) glycine deleted]: a new unstable variant expressing cyanosis. Hemoglobin 17: 467-473, 1993. [PubMed: 8294206, related citations] [Full Text]

  359. Gacon, G., Belkhodja, O., Wajcman, H., Labie, D., Najman, A. Structural and functional studies of Hb Rothschild (beta 37 (C3) trp-to-arg): a new variant of the alpha-1-beta-2 contact. FEBS Lett. 82: 243-246, 1977. [PubMed: 913596, related citations] [Full Text]

  360. Gacon, G., Krishnamoorthy, R., Wajcman, H., Labie, D., Tapon, J., Cosson, A. Hemoglobin Djelfa beta 98 (FG5) val-to-ala: isolation and functional properties of the heme saturated form. Biochim. Biophys. Acta 490: 156-163, 1977. [PubMed: 13850, related citations] [Full Text]

  361. Gacon, G., Wajcman, H., Labie, D. Structural and functional study of Hb Nancy beta145 (HC2) tyr-to-asp: a high oxygen affinity hemoglobin. FEBS Lett. 56: 39-42, 1975. [PubMed: 239863, related citations] [Full Text]

  362. Galacteros, F., Delanoe-Garin, J., Monplaisir, N., Arous, N., Blouquit, Y., Mamalaki, A., Tulliez, M., Ouka, M., Goossens, M., Rosa, J. Two new cases of heterozygosity for hemoglobin Knossos alpha-2,beta-2 27 ala-to-ser detected in the French West Indies and Algeria. Hemoglobin 8: 215-228, 1984. [PubMed: 6469698, related citations] [Full Text]

  363. Galanello, R., Perseu, L., Barella, S., Satta, S., Fais, A., Era, B., Corda, M. Hb Belfast [beta-15(A12)trp-to-arg]: definition of the clinical and hematological phenotype. Hemoglobin 28: 217-222, 2004. [PubMed: 15481889, related citations] [Full Text]

  364. Gale, R. E., Blair, N. E., Huehns, E. R., Clegg, J. B. Hb A-like sickle haemoglobin: Hb S-Providence. Brit. J. Haemat. 70: 251-252, 1988. [PubMed: 3191036, related citations] [Full Text]

  365. Gallienne, A. E., Dreau, H. M., McCarthy, J., Timbs, A. T., Hampson, J. M., Schuh, A., Old, J. M., Henderson, S. J. Multiplex ligation-dependent probe amplification identification of 17 different beta-globin gene deletions (including four novel mutations) in the UK population. Hemoglobin 33: 406-416, 2009. [PubMed: 19958185, related citations] [Full Text]

  366. Game, L., Bergounioux, J., Close, J. P., Marzouka, B. E., Thein, S. L. A novel deletion causing (episilon-gamma-delta-beta)O thalassemia in a Chilean family. Brit. J. Haemat. 123: 154-159, 2003. [PubMed: 14510959, related citations] [Full Text]

  367. Gammack, D. B., Huehns, E. R., Lehmann, H., Shooter, E. M. The abnormal polypeptide chains in a number of haemoglobin variants. Acta Genet. Statist. Med. 11: 1-16, 1961. [PubMed: 13703277, related citations] [Full Text]

  368. Garel, M. C., Blouquit, Y., Arous, N., Rosa, J. Hb Strasbourg beta 20 (B2) val-to-asp: a variant at the same locus as Hb Olympia beta 20 val-to-met. FEBS Lett. 72: 1-4, 1976. [PubMed: 1001451, related citations] [Full Text]

  369. Garel, M. C., Blouquit, Y., Rosa, J. Hemoglobin Castilla (beta 32 (B14) leu-to-arg): a new unstable variant producing severe hemolytic disease. FEBS Lett. 58: 144-148, 1975. [PubMed: 1225574, related citations] [Full Text]

  370. Garel, M. C., Hassan, W., Coquelet, M. T., Goossens, M., Rosa, J., Arous, N. Hemoglobin J(Cairo): beta 65(E9) lys-to-gln, a new hemoglobin variant discovered in an Egyptian family. Biochim. Biophys. Acta 420: 97-104, 1976. [PubMed: 1247583, related citations] [Full Text]

  371. Garewal, G., Fearon, C. W., Warren, T. C., Marwaha, N., Marwaha, R. K., Mahadik, C., Kazazian, H. H., Jr. The molecular basis of beta thalassaemia in Punjabi and Maharashtran Indians includes a multilocus aetiology involving triplicated alpha-globin loci. Brit. J. Haemat. 86: 372-376, 1994. [PubMed: 8199027, related citations] [Full Text]

  372. Gaudry, C. L., Jr., Pitel, P. A., Jue, D. L., Hine, T. K., Johnson, M. H., Moo-Penn, W. F. Hb Jacksonville [beta54(D5)val-to-asp]: a new unstable variant found in a patient with hemolytic anemia. Hemoglobin 14: 653-659, 1990. [PubMed: 2101840, related citations]

  373. Geever, R. F., Wilson, L. B., Nallaseth, F. S., Milner, P. F., Bittner, M., Wilson, J. T. Direct identification of sickle cell anemia by blot hybridization. Proc. Nat. Acad. Sci. 78: 5081-5085, 1981. [PubMed: 6272289, related citations] [Full Text]

  374. George, P. M., Myles, T., Williamson, D., Higuchi, R., Symmans, W. A., Brennan, S. O. A family with haemolytic anaemia and three beta-globins: the deletion in haemoglobin Atlanta-Coventry (beta75 leu-to-pro, 141 leu deleted) is not present at the nucleotide level. Brit. J. Haemat. 81: 93-98, 1992. [PubMed: 1520631, related citations] [Full Text]

  375. Gerald, P. S., Efron, M. L. Chemical studies of several varieties of Hb M. Proc. Nat. Acad. Sci. 47: 1758-1767, 1961. [PubMed: 13897827, related citations] [Full Text]

  376. Gerald, P. S., George, P. Second spectroscopically abnormal methemoglobin associated with hereditary cyanosis. Science 129: 393-394, 1959. [PubMed: 13634986, related citations] [Full Text]

  377. Gerhard, D. S., Jones, C., Morse, H. G., Handelin, B., Weeks, V., Housman, D. Analysis of human chromosome 11 by somatic cell genetics: reexamination of derivatives of human-hamster cell line J1. Somat. Cell Molec. Genet. 13: 293-304, 1987. [PubMed: 3331828, related citations] [Full Text]

  378. Gerhard, D. S., Kidd, K. K., Kidd, J. R., Egeland, J. A., Housman, D. E. Identification of a recent recombination event within the human beta-globin gene cluster. Proc. Nat. Acad. Sci. 81: 7875-7879, 1984. [PubMed: 6096866, related citations] [Full Text]

  379. Geva, A., Clark, J. J., Zhang, Y., Popowicz, A., Manning, J. M., Neufeld, E. J. Hemoglobin Jamaica Plain--a sickling hemoglobin with reduced oxygen affinity. New Eng. J. Med. 351: 1532-1538, 2004. [PubMed: 15470216, related citations] [Full Text]

  380. Giambona, A., Vinciguerra, M., Cassara, F., Li Muli, R., Leto, F., Passarello, C., Wajcman, H., Maggio, A. Hb Marineo [beta-70 (E14) ala-to-val]: a silent hemoglobin variant with a mutation within the heme pocket. Hemoglobin 30: 139-148, 2006. [PubMed: 16798637, related citations] [Full Text]

  381. Giardina, B., Brunori, M., Antonini, E., Tentori, L. Properties of hemoglobin G Ferrara (beta 57(E1) asn-to-lys). Biochim. Biophys. Acta 534: 1-6, 1978. [PubMed: 26414, related citations] [Full Text]

  382. Gibb, E. A. Increased subunit association of a new superstable variant hemoglobin Motown. Clin. Res. 29: 795A, 1981. Note: Sponsored by D. L. Rucknagel.

  383. Gilbert, A. T., Fleming, P. J., Hertzberg, M. S. A second case of Hb Bologna-St. Orsola (beta-146(HC3)his-to-tyr) in an unrelated family of Anglo-Celtic origin. Hemoglobin 24: 139-142, 2000. [PubMed: 10870885, related citations] [Full Text]

  384. Gilbert, A. T., Fleming, P. J., Hertzberg, M. S. Two unrelated cases of Hb Old Dominion/Burton-upon-Trent (beta-143(H21)his-to-tyr): a rare variant causing spuriously elevated Hb A(1C) values. Hemoglobin 24: 163-164, 2000. [PubMed: 10870890, related citations] [Full Text]

  385. Gilbert, A. T., Fleming, P. J., Sumner, D. R., Hughes, W. G., Holland, R. A. B., Tibben, E. A. Hemoglobin Windsor or beta-11 (A8) val-to-asp: a new unstable beta-chain hemoglobin variant producing a hemolytic anemia. Hemoglobin 13: 437-453, 1989. [PubMed: 2599880, related citations] [Full Text]

  386. Gilbert, A. T., Fleming, P. J., Sumner, D. R., Hughes, W. G., Ip, F., Kwan, Y. L., Holland, R. A. B. Hemoglobin Randwick or beta15 (A12) trp-to-gly: a new unstable beta-chain hemoglobin variant. Hemoglobin 12: 149-161, 1988. [PubMed: 3384707, related citations] [Full Text]

  387. Giordano, P. C., Harteveld, C. L., Bernini, L. F., Doorduijn, J. K., Geenen, A. A., Kok, P. J. M., Versteegh, F. G. A. Haplotype analysis of two new, independent cases of Hb Osu-Christiansborg. Hemoglobin 23: 193-195, 1999. [PubMed: 10335988, related citations] [Full Text]

  388. Girodon, E., Ghanem, N., Vidaud, M., Riou, J., Martin, J., Galacteros, F., Goossens, M. Rapid molecular characterization of mutations leading to unstable hemoglobin beta-chain variants. Ann. Hemat. 65: 188-192, 1992. [PubMed: 1420507, related citations] [Full Text]

  389. Glynn, K. P., Penner, J. A., Smith, J. R. Familial erythrocytosis: a description of three families, one with hemoglobin Ypsilanti. Ann. Intern. Med. 69: 769-776, 1968. [PubMed: 5687529, related citations] [Full Text]

  390. Goldsmith, M. E., Humphries, R. K., Ley, T., Cline, A., Kantor, J. A., Nienhuis, A. W. Silent substitution in beta-plus-thalassemia gene activating a cryptic splice site in beta-globin RNA coding sequence. Proc. Nat. Acad. Sci. 80: 2318-2322, 1983. [PubMed: 6572978, related citations] [Full Text]

  391. Gonzalez-Redondo, J. M., Kattamis, C., Huisman, T. H. J. Characterization of three types of beta-0-thalassemia resulting from a partial deletion of the beta-globin gene. Hemoglobin 13: 377-392, 1989. [PubMed: 2753736, related citations] [Full Text]

  392. Gonzalez-Redondo, J. M., Sicilia, A., Murga, M. J., Kutlar, A., Wilson, J. B., Huisman, T. H. J. Hb E-Saskatoon or beta22(B4)glu-to-lys in a Spanish family. Hemoglobin 11: 35-38, 1987. [PubMed: 3108201, related citations] [Full Text]

  393. Gonzalez-Redondo, J. M., Stoming, T. A., Kutlar, F., Kutlar, A., Hu, H., Wilson, J. B., Huisman, T. H. J. Hb Monroe or beta30 (B12) arg-to-thr, a variant associated with beta-thalassemia due to a G-to-C substitution adjacent to the donor splice site of the first intron. Hemoglobin 13: 67-74, 1989. [PubMed: 2539344, related citations] [Full Text]

  394. Gonzalez-Redondo, J. M., Stoming, T. A., Lanclos, K. D., Gu, Y. C., Kutlar, A., Kutlar, F., Nakatsuji, T., Deng, B., Han, I. S., McKie, V. C., Huisman, T. H. J. Clinical and genetic heterogeneity in black patients with homozygous beta-thalassemia from the southeastern United States. Blood 72: 1007-1014, 1988. [PubMed: 2458145, related citations]

  395. Goossens, M., Garel, M. C., Auvinet, J., Basset, P., Ferreira Gomes, P., Rosa, J. Hemoglobin C Ziguinchor beta 6 glu-to-val and beta 58 pro-to-arg: the second sickling variant with amino acid substitutions in 2 residues of the beta polypeptide chain. FEBS Lett. 58: 149-154, 1975. [PubMed: 1225575, related citations] [Full Text]

  396. Gordon-Smith, E. C., Dacie, J. V., Blecher, T. E., French, E. A., Wiltshirre, B. G., Lehmann, H. Haemoglobin Nottingham, beta FG 5(98) val-to-gly: a new unstable haemoglobin producing severe haemolysis. Proc. Roy. Soc. Med. 66: 507-508, 1973. [PubMed: 4781799, related citations]

  397. Gottlieb, A. J., Robinson, E. A., Itano, H. A. Primary structure of Hopkins-1 haemoglobin-A. Nature 214: 189-190, 1967. [PubMed: 6034218, related citations] [Full Text]

  398. Gouagna, L. C., Bancone, G., Yao, F., Yameogo, B., Dabire, K. R., Costantini, C., Simpore, J., Ouedraogo, J. B., Modiano, D. Genetic variation in human HBB is associated with Plasmodium falciparum transmission. Nature Genet. 42: 328-331, 2010. [PubMed: 20305663, related citations] [Full Text]

  399. Greaves, D. R., Fraser, P., Vidal, M. A., Hedges, M. J., Ropers, D., Luzzatto, L., Grosveld, F. A transgenic mouse model of sickle cell disorder. Nature 343: 183-185, 1990. [PubMed: 2296310, related citations] [Full Text]

  400. Greer, J., Perutz, M. F. Three dimensional structure of haemoglobin Rainier. Nature 230: 261-264, 1971.

  401. Grignoli, C. R. E., Wenning, M. R. S. C., Sonati, M. F., Kimura, E. M., Arruda, V. R., Saad, S. T. O., Costa, F. F. Hb Rio Clara [beta-34(B16)val to met]: a novel electrophoretically silent variant found in association with Hb Hasharon [alpha-47(CE5)asp to his] and alpha-thalassemia-2 (-alpha-3.7). Hemoglobin 23: 177-182, 1999. [PubMed: 10335985, related citations] [Full Text]

  402. Groff, P., Kalmes, G., Golinska, B., Miyazaki, A., Riou, J., Carte, N., Prome, D., Kister, J., Galacteros, F., Wajcman, H. Hb Ernz (beta-123(H1)thr-to-asn) and Hb Renert (beta-133(H11)val-to-ala): two new neutral variants revealed by reversed phase high performance liquid chromatography analysis. Hemoglobin 24: 287-297, 2000. [PubMed: 11186258, related citations] [Full Text]

  403. Grosveld, F., van Assendelft, G. B., Greaves, D. R., Kollias, G. Position-independent, high-level expression of the human beta-globin gene in transgenic mice. Cell 51: 975-985, 1987. [PubMed: 3690667, related citations] [Full Text]

  404. Gu, L.-H., Leonova, J. Y., Huisman, T. H. J. Hb S-Hb Lufkin disease in a black male patient. Hemoglobin 19: 291-294, 1995. [PubMed: 8537234, related citations] [Full Text]

  405. Gurgey, A., Altay, C., Gu, L.-H., Leonova, J. Y., Delibalta, A., Oner, C., Huisman, T. H. J. Hb Hakkari or alpha(2)beta(2)31(B13)leu-to-arg, a severely unstable hemoglobin variant associated with numerous intra-erythroblastic inclusions and erythroid hyperplasia of the bone marrow. Hemoglobin 19: 165-172, 1995. [PubMed: 7558872, related citations] [Full Text]

  406. Gurgey, A., Sipahioglu, M., Aksoy, M. Compound heterozygosity for Hb E-Saskatoon or beta22(B4)glu-to-lys and beta-thalassemia type IVS-I-6 (T-to-C). Hemoglobin 14: 449-451, 1990. [PubMed: 2283299, related citations] [Full Text]

  407. Gurney, H., Baig, I., Gordon, S., Phadke, K., Kearsley, H., Fleming, P., Wyatt, K., Hughes, W. A second Australian family with hemoglobin North Shore (beta134 val-to-glu). Pathology 19: 62-63, 1987. [PubMed: 3588028, related citations] [Full Text]

  408. Gusella, J., Varsanyi-Breiner, A., Kao, F.-T., Jones, C., Puck, T. T., Keys, C., Orkin, S., Housman, D. Precise localization of human beta-globin gene complex on chromosome 11. Proc. Nat. Acad. Sci. 76: 5239-5243, 1979. [PubMed: 291941, related citations] [Full Text]

  409. Haigh, L. S., Anderson, W. F., Francke, U. Regional mapping of the beta-globin gene on 11p. (Abstract) Cytogenet. Cell Genet. 25: 162-163, 1979.

  410. Hall, G. W., Sampietro, M., Barnetson, R., Fitzgerald, J., McCann, S., Thein, S. Meiotic recombination in an Irish family with beta-thalassaemia. Hum. Genet. 92: 28-32, 1993. [PubMed: 8103502, related citations] [Full Text]

  411. Hamaguchi, K., Kusuda, Y., Yoshimichi, G., Hanada, R., Harano, K., Harano, T., Sakata, T. Hb I-High Wycombe (beta-59(E3)lys-to-glu): the first instance in Japan. Hemoglobin 24: 153-156, 2000. [PubMed: 10870888, related citations] [Full Text]

  412. Hamilton, H. B., Iuchi, I., Miyaji, T., Shibata, S. Hemoglobin Hiroshima (beta 143 histidine to aspartic acid): a newly identified fast moving beta chain variant associated with increased oxygen affinity and compensatory erythremia. J. Clin. Invest. 48: 525-535, 1969. [PubMed: 5773089, related citations] [Full Text]

  413. Han, J. Y., Wee, J. H., Kim, J. M., Kim, J. Y., Kim, I. H., Rodgers, G. P. A new observation of Hb Yamagata with a different nucleotide substitution: beta-132 AAA-to-AAT. Hemoglobin 20: 165-168, 1996. [PubMed: 8811322, related citations] [Full Text]

  414. Hanada, M., Ohta, Y., Imamura, T., Fejimura, T., Kawasaki, K., Kosaka, K., Yamaoka, K., Seita, M. Studies of abnormal hemoglobins in western Japan. (Abstract) Jpn. J. Hum. Genet. 9: 253-254, 1964.

  415. Harano, K., Harano, T., Koide, G., Akimaru, S. Hb Nakano [beta-8(lys-to-met)]: a new beta chain variant found in a Japanese woman. Hemoglobin 19: 397-401, 1995. [PubMed: 8718698, related citations] [Full Text]

  416. Harano, K., Harano, T., Shibata, S., Ueda, S., Mori, H., Seki, M. Hb Okazaki (beta93(F8)cys-to-arg): a new hemoglobin variant with increased oxygen affinity and instability. FEBS Lett. 173: 45-47, 1984. Note: Abstract: Hemoglobin 9: 109 only, 1985. [PubMed: 6745435, related citations] [Full Text]

  417. Harano, K., Harano, T., Ueda, S., Mori, H., Shibata, S., Takeda, I., Tsunematsu, T. Hb Tacoma (beta30[B12] arg-to-ser), a slightly unstable hemoglobin variant found in Japan. Hemoglobin 9: 635-639, 1985. [PubMed: 3937827, related citations] [Full Text]

  418. Harano, K., Harano, T., Ueda, S., Ohkushi, T., Imai, K. A new hemoglobin variant, Hb Mito (beta144 (HC1) lys-to-glu) with increased oxygen affinity. FEBS Lett. 192: 75-78, 1985. [PubMed: 2865170, related citations] [Full Text]

  419. Harano, T., Harano, K., Katsuki, T. Hb Yaizu (beta79(EF3)asp--asn): a new beta chain variant found in a Japanese female. Hemoglobin 19: 21-25, 1995. [PubMed: 7615399, related citations] [Full Text]

  420. Harano, T., Harano, K., Kushida, Y., Imai, K., Nishinakamura, R., Matsunaga, T. Hb Kodaira [beta-146(HC3)his-to-gln]: a new beta chain variant with an amino acid substitution at the C-terminus. Hemoglobin 16: 85-91, 1992. [PubMed: 1634367, related citations] [Full Text]

  421. Harano, T., Harano, K., Kushida, Y., Ueda, S., Kawakami, H. Hb J-Amiens [beta17(A14)lys-to-asn] found in a Japanese. Hemoglobin 14: 445-448, 1990. [PubMed: 2101004, related citations] [Full Text]

  422. Harano, T., Harano, K., Kushida, Y., Ueda, S., Yoshii, A., Nishinarita, M. Hb Isehara (or Hb Redondo) [beta-92(F8)his-to-asn]: an unstable variant with proximal histidine substitution at the heme contact. Hemoglobin 15: 279-290, 1991. [PubMed: 1787097, related citations] [Full Text]

  423. Harano, T., Harano, K., Kushida, Y., Ueda, S. Structural analysis of abnormal hemoglobin by the polymerase chain reaction. Jpn. J. Clin. Path. 38: 1067-1072, 1990.

  424. Harano, T., Harano, K., Kushida, Y., Ueda, S. A new abnormal variant, Hb Yahata or beta-112(G14)cys-to-tyr, found in a Japanese: structural confirmation by DNA sequencing of the beta-globin gene. Hemoglobin 15: 109-113, 1991. [PubMed: 1917530, related citations] [Full Text]

  425. Harano, T., Harano, K., Shibata, S., Ueda, S., Mori, H., Arimasa, N. Hemoglobin Okayama (beta 2 (NA2) his replaced by gln): a new 'silent' hemoglobin variant with substituted amino acid residue at the 2,3-diphosphoglycerate binding site. FEBS Lett. 156: 20-22, 1983. [PubMed: 6852251, related citations] [Full Text]

  426. Harano, T., Harano, K., Ueda, S., Imai, K., Marubashi, S. Hb Yamagata (beta132(H10)lys-to-asn): a new abnormal hemoglobin in a Japanese family. Hemoglobin 14: 207-211, 1990. [PubMed: 2272843, related citations] [Full Text]

  427. Harano, T., Harano, K., Ueda, S., Imai, K., Ohkuma, A., Koya, Y., Takahashi, H. Hb Fukuoka (beta2(NA2)his-to-tyr): a new mutation at the 2,3-diphosphoglycerate binding site. Hemoglobin 14: 199-205, 1990. [PubMed: 2272842, related citations] [Full Text]

  428. Harano, T., Harano, K., Ueda, S., Imai, N., Kitazumi, T. A new electrophoretically-silent hemoglobin variant: hemoglobin Kofu or beta84 (EF8) thr-to-ile. Hemoglobin 10: 417-420, 1986. [PubMed: 3744871, related citations] [Full Text]

  429. Harano, T., Harano, K., Ueda, S., Nakaya, K. Hb D Los Angeles (beta121 glu-to-gln) in Japan. Hemoglobin 11: 177-180, 1987. [PubMed: 2887538, related citations] [Full Text]

  430. Harano, T., Harano, K., Ueda, S., Nomura, Y., Nanjo, K., Miyamura, T. Beta-zero-thalassemia due to a nonsense mutation (beta-90 GAG-to-TAG). (Abstract) Acta Haemat. Jpn. 52: 410, 1989.

  431. Harano, T., Harano, K., Ueda, S., Shibata, S., Imai, K., Nakai, T. Hb Hope (beta136 (H14) gly-to-asp) in a Japanese family. Hemoglobin 7: 263-265, 1983. [PubMed: 6874374, related citations] [Full Text]

  432. Harano, T., Harano, K., Ueda, S., Shibata, S., Imai, K., Seki, M. Hemoglobin Machida (beta6 (A3) glu-to-gln), a new abnormal hemoglobin discovered in a Japanese family: structure, function and biosynthesis. Hemoglobin 6: 531-535, 1982. [PubMed: 6129204, related citations] [Full Text]

  433. Harano, T., Harano, K., Ueda, S., Shibata, S., Imai, K. Hemoglobin Ankara (beta10 (A7) ala-to-asp): properties and biosynthesis. Hemoglobin 5: 737-741, 1981. [PubMed: 7338476, related citations]

  434. Harano, T., Harano, K., Ueda, S., Shibata, S., Iuchi, I., Mizushima, J., Matsumoto, T., Harada, H. Hemoglobin Yusa (beta21(B3) asp-to-tyr), a new abnormal hemoglobin found in Japan. Hemoglobin 5: 121-131, 1981. [PubMed: 7216815, related citations] [Full Text]

  435. Hardison, R. C., Chui, D. H. K., Giardine, B., Riemer, C., Patrinos, G. P., Anagnou, N., Miller, W., Wajcman, H. HbVar: a relational database of human hemoglobin variants and thalassemia mutations at the globin gene server. Hum. Mutat. 19: 225-233, 2002. [PubMed: 11857738, related citations] [Full Text]

  436. Harkness, D. R., Yu, C. K., Goldberg, M., Bradley, T. B. Novel studies on a 'silent' high affinity mutant hemoglobin (San Diego, beta 109 val-to-met). Hemoglobin 5: 33-46, 1981. [PubMed: 7204093, related citations] [Full Text]

  437. Harteveld, C. L., Groeneveld, J. H. M., van Dam, B., Van Delft, P., Akkerman, N., Arkesteijn, S., Giordano, P. C. Hb Zoeterwoude (beta-23(B5)val-to-ala): a new beta-globin variant found in association with erythrocytosis. Hemoglobin 29: 11-17, 2005. [PubMed: 15768551, related citations]

  438. Harteveld, C. L., Osborne, C. S., Peters, M., van der Werf, S., Plug, R., Fraser, P., Giordano, P. C. Novel 112 kb (epsilon-G-gamma-A-gamma) delta-beta-thalassaemia deletion in a Dutch family. Brit. J. Haemat. 122: 855-858, 2003. [PubMed: 12930401, related citations] [Full Text]

  439. Harteveld, C. L., Thelen, M. H. M., Rutten, J. J. A., Leuverman, J., Akkermans, N., van Delft, P., Arkesteijn, S., Giordano, P. C. Hb Geldrop St. Anna (beta-94(FG1)asp-to-tyr): a new hemoglobin variant observed in a diabetic patient. Hemoglobin 29: 107-112, 2005. [PubMed: 15921162, related citations]

  440. Harteveld, C., Plug, R. J., Van Delft, P., Van Helden, W. C. H., Giordano, P. C. Hb 't Lange Land [beta-136(H14)gly-arg]: A new hemoglobin variant described in a Dutch patient of Chinese origin. Hemoglobin 25: 331-336, 2001. [PubMed: 11570727, related citations] [Full Text]

  441. Harthoorn-Lasthuizen, E. J., Nabben, F. A. E., Kazanetz, E. G., Gu, L.-H., Molchanova, T. P., Huisman, T. H. J. Hb Mizuho or alpha(2)beta(2)68(E12)leu-to-pro in a young Dutch boy. Hemoglobin 19: 203-206, 1995. [PubMed: 7558877, related citations] [Full Text]

  442. Hassan, W., Basset, P., Oudart, J. L., Goossens, M., Rosa, J. Properties of the double substituted hemoglobin C Ziguinchor (beta 6 glu-to-val 58 pro-to-arg). Hemoglobin 1: 487-501, 1977. [PubMed: 893143, related citations] [Full Text]

  443. Hatton, C. S. R., Wilkie, A. O. M., Drysdale, H. C., Wood, W. G., Vickers, M. A., Sharpe, J., Ayyub, H., Pretorius, I. M., Buckle, V. J., Higgs, D. R. Alpha-thalassemia caused by a large (62 kb) deletion upstream of the human alpha-globin gene cluster. Blood 76: 221-227, 1990. [PubMed: 2364173, related citations]

  444. Hattori, Y., Okayama, N., Ohba, Y., Yamashiro, Y., Yamamoto, K., Yamamoto, K., Koyama, S., Sawada, U. A new beta-thalassemia allele, codon 26 (GAG-to-GTAG), found in a Japanese. Hemoglobin 22: 79-82, 1998. [PubMed: 9494052, related citations] [Full Text]

  445. Hattori, Y., Yamamoto, K., Yamashiro, Y., Ohba, Y., Miyamura, S., Yamamoto, K., Matsuno, Y., Morishita, M., Miyaji, T., Era, T. Three beta-thalassemia mutations in the Japanese: IVS-II-1 (G-to-A), IVS-II-848 (C-to-G), and codon 90 (GAG-to-TAG). Hemoglobin 16: 93-97, 1992. [PubMed: 1634368, related citations] [Full Text]

  446. Hattori, Y., Yamane, A., Yamashiro, Y., Matsuno, Y., Yamamoto, K., Yamamoto, K., Ohba, Y., Miyaji, T. Characterization of beta-thalassemia mutations among the Japanese. Hemoglobin 13: 657-670, 1989. [PubMed: 2634667, related citations] [Full Text]

  447. Hayashi, A., Stamatoyannopoulos, G., Yoshida, A., Adamson, J. Haemoglobin Rainier: beta 145 (HC2) tyrosine to cysteine and haemoglobin Bethesda: beta 145 (HC2) tyrosine to histidine. Nature N. B. 230: 264-267, 1971. [PubMed: 5282843, related citations] [Full Text]

  448. Hayashi, A., Suzuki, T., Imai, K., Morimoto, H., Watari, H. Properties of hemoglobin M, Milwaukee-1 variant and its unique characteristic. Biochim. Biophys. Acta 194: 6-15, 1969. [PubMed: 4311041, related citations] [Full Text]

  449. Hebbel, R. P., Eaton, J. W., Kronenberg, R. S., Zajani, E. D., Moore, L. G., Berger, E. M. Human llamas: adaptation to altitude in subjects with high hemoglobin oxygen affinity. J. Clin. Invest. 62: 593-600, 1978. [PubMed: 29054, related citations] [Full Text]

  450. Hebbel, R. P., Kronenberg, R. S., Eaton, J. W. Hypoxic ventilatory response in subjects with normal and high oxygen affinity hemoglobins. J. Clin. Invest. 60: 1211-1215, 1977. [PubMed: 908760, related citations] [Full Text]

  451. Heck, W., Wolf, H. Angeborener Herzfehler mit Cyanose durch pathologischen Blutfarbstoff (Hb-M). Ann. Paediat. 190: 135-146, 1958. [PubMed: 13509426, related citations]

  452. Hedlund, B., Paine, S., Smith, C. M., II, Raines, J., Morrison, W. T., Adams, J. G., III. Hemoglobin Minneapolis-Laos (beta118 (GH1) phe-to-tyr): a new hemoglobin variant with normal functional properties. Hemoglobin 8: 75-78, 1984. [PubMed: 6547119, related citations] [Full Text]

  453. Hedrick, P. Estimation of relative fitnesses from relative risk data and the predicted future of haemoglobin alleles S and C. J. Evol. Biol. 17: 221-224, 2004. [PubMed: 15000665, related citations] [Full Text]

  454. Heller, P., Coleman, R. D., Yakulis, V. Hemoglobin M (Hyde Park): a new variant of abnormal methemoglobin in a Negro. (Abstract) J. Clin. Invest. 45: 1021, 1966.

  455. Heller, P., Yakulis, V. J., Rosenzweig, A. I., Abildgaard, C. F., Rucknagel, D. L. Mild homozygous beta-thalassemia: further evidence for the heterogeneity of beta-thalassemia genes. Ann. Intern. Med. 64: 52-61, 1966. [PubMed: 5900783, related citations] [Full Text]

  456. Heller, P. Hemoglobin M (Chicago) and M (Kankakee). In: Lehmann, H.; Betke, K.: Haemoglobin-Colloquium. Stuttgart: Georg Thieme Verlag (pub.) 1962. Pp. 47-49.

  457. Henthorn, J. S., Wajcman, H., Prome, D., Riou, J., Kister, J., Baudin-Creuza, V., Davies, S. C., Galacteros, F. Hb Harrow (beta-118(GH1)phe-to-cys): a new neutral hemoglobin variant. Hemoglobin 23: 273-279, 1999. [PubMed: 10490141, related citations] [Full Text]

  458. Herrick, J. B. Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia. Arch. Intern. Med. 6: 517-521, 1910.

  459. Heusterspreute, M., Derclaye, I., Gala, J.-L., Van Geet, C., Ferrant, A., Malchaire, Y., Thonnard, J., Vaerman, J.-L., Philippe, M. Beta-thalassaemia in indigenous Belgian families: identification of a novel mutation. Hum. Genet. 98: 77-79, 1996. [PubMed: 8682512, related citations] [Full Text]

  460. Hidaka, K., Iuchi, I., Miyake, K., Nakahara, H., Iwakawa, G. Hb Fukuyama (beta77 (IF1) his-to-tyr): a new abnormal hemoglobin discovered in a Japanese. Hemoglobin 12: 391-394, 1988. [PubMed: 3170240, related citations] [Full Text]

  461. Hill, R. L., Schwartz, H. C. A chemical abnormality in haemoglobin G. Nature 184: 641-642, 1959.

  462. Hill, R. L., Swenson, R. T., Schwartz, H. C. Characterization of a chemical abnormality in hemoglobin G. J. Biol. Chem. 235: 3182-3187, 1960. [PubMed: 13714317, related citations]

  463. Hirano, M., Ohba, Y., Imai, K., Ino, T., Morishita, Y., Matsui, T., Shimizu, S., Sumi, H., Yamamoto, K., Miyaji, T. Hb Toyoake: beta 142 (H20) ala-to-pro: a new unstable hemoglobin with high oxygen affinity. Blood 57: 697-704, 1981. [PubMed: 7470620, related citations]

  464. Hobolth, N. Haemoglobin M Arhus: I. Clinical family study. Acta Paediat. Scand. 54: 357-362, 1965.

  465. Hojas-Bernal, R., McNab-Martin, P., Fairbanks, V. F., Holmes, M. W., Hoyer, J. D., McCormick, D. J., Kubik, K. S. Hb Chile [beta-28(B10)leu to met]: an unstable hemoglobin associated with chronic methemoglobinemia and sulfonamide or methylene blue-induced hemolytic anemia. Hemoglobin 23: 125-134, 1999. [PubMed: 10335980, related citations] [Full Text]

  466. Hollender, A., Lorkin, P. A., Lehmann, H., Svensson, B. New unstable haemoglobin Boras: beta 88 (F4) leucine-arginine. Nature 222: 953-955, 1969. [PubMed: 5789325, related citations] [Full Text]

  467. Honig, G. R., Green, D., Shamsuddin, M., Vida, L. N., Mason, R. G., Gnarra, D. J., Maurer, H. S. Hemoglobin Abraham Lincoln, beta 32 (beta 14) leucine to proline: an unstable variant producing severe hemolytic disease. J. Clin. Invest. 52: 1746-1755, 1973. [PubMed: 4352462, related citations] [Full Text]

  468. Honig, G. R., Mason, R. G., Shamsuddin, M., Vida, L. N., Rao, K. R. P., Patel, A. R. Two new sickle cell syndromes: Hb S, Hb Camden, and alpha-thalassemia and Hb S in combination with Hb Tacoma. Blood 55: 655-660, 1980. [PubMed: 7357091, related citations]

  469. Honig, G. R., Seeler, R. A., Shamsuddin, M., Vida, L. N., Mompoint, M., Valcourt, E. Hemoglobin Korle Bu in a Mexican family. Hemoglobin 7: 185-189, 1983. [PubMed: 6671904, related citations] [Full Text]

  470. Honig, G. R., Shamsuddin, M., Mason, R. G., Vida, L. N. Hemoglobin Lincoln Park: a beta-delta fusion (anti-Lepore) variant with an amino acid deletion in the delta chain-derived segment. Proc. Nat. Acad. Sci. 75: 1475-1479, 1978. [PubMed: 274735, related citations] [Full Text]

  471. Honig, G. R., Vida, L. N., Latorraca, R., Divgi, A. B. Hb South Milwaukee (beta105 (G7) leu-to-phe): a newly-identified hemoglobin variant with high oxygen affinity. Am. J. Hemat. 34: 199-203, 1990. [PubMed: 2363414, related citations] [Full Text]

  472. Honig, G. R., Vida, L. N., Rosenblum, B. B., Perutz, M. F., Fermi, G. Hemoglobin Warsaw (phe-beta-42(CD1)-to-val), an unstable variant with decreased oxygen affinity: characterization of its synthesis, functional properties, and structure. J. Biol. Chem. 265: 126-132, 1990. [PubMed: 2294098, related citations]

  473. Hopmeier, P., Binder, C., Gadner, H., Fischer, M. A case of the unstable Hb Genova (beta28 leu-to-pro) in an Arab child associated with severe haemolytic anaemia and growth retardation. Acta Haemat. 83: 39-41, 1990. [PubMed: 2105568, related citations] [Full Text]

  474. Horlein, H., Weber, G. Ueber chronische familiaere Methaemoglobinaemia und eine neue Modifikation des methaemoglobins. Dtsch. Med. Wschr. 73: 476-478, 1948. [PubMed: 18105244, related citations] [Full Text]

  475. Horst, J., Oehme, R., Epplen, J. T., Kohne, E. Haemoglobin Freiburg: direct detection by synthetic oligonucleotide probes. Hum. Genet. 79: 172-174, 1988. [PubMed: 3391614, related citations] [Full Text]

  476. Horst, J., Oehme, R., Kleihauer, E., Kohne, E. DNA restriction mapping identifies the chromosome carrying the mutant Hb Presbyterian beta-globin gene. Hum. Genet. 64: 263-266, 1983. [PubMed: 6309649, related citations] [Full Text]

  477. Horst, J., Oehme, R., Kohne, E. Hemoglobin Koln: direct analysis of the gene mutation by synthetic DNA probes. Blood 68: 1175-1177, 1986. [PubMed: 3768534, related citations]

  478. Horst, J., Schafer, R., Kleihauer, E., Kohne, E. Analysis of the Hb M Milwaukee mutation at the DNA level. Brit. J. Haemat. 54: 643-648, 1983. [PubMed: 6307336, related citations] [Full Text]

  479. Housman, D., Gusella, J., Kao, F. T., Jones, C., Breiner, A., Keys, C., Orkin, S., Puck, T. T. Regional mapping of the human structural gene for hemoglobin beta on chromosome 11 using restriction endonuclease mapping and a regional clone panel. (Abstract) Cytogenet. Cell Genet. 25: 166, 1979.

  480. Housman, D. Personal Communication. Cambridge, Mass. 6/1979.

  481. Hoyer, J. D., Weinhold, J., Mailhot, E., Alter, D., McCormick, D. J., Snow, K., Kubik, K. S., Holmes, M. W., Fairbanks, V. F. Three new hemoglobin variants with abnormal oxygen affinity: Hb Saratoga Springs [alpha-40(C5)lys-to-asn (alpha-1)], Hb Santa Clara [beta-97(FG4)his-to-asn], and Hb Sparta [beta-103(G5)phe-to-val]. Hemoglobin 27: 235-241, 2003. [PubMed: 14649314, related citations] [Full Text]

  482. Hoyer, J. D., Wick, M. J., Thibodeau, S. N., Kechteiger, K. S., Cook, J. D., Fairbanks, V. F. Hb Silver Springs [beta-131(H9)gln-to-his], a new hemoglobin variant found in six African-Americans. Hemoglobin 22: 37-44, 1998. [PubMed: 9494046, related citations] [Full Text]

  483. Hoyer, J. D., Wick, M. J., Thibodeau, S. N., Viker, K. A., Conner, R., Fairbanks, V. F. Hb Tak confirmed by DNA analysis: not expressed as thalassemia in a Hb Tak/Hb E compound heterozygote. Hemoglobin 22: 45-52, 1998. [PubMed: 9494047, related citations] [Full Text]

  484. Huang, S., Wong, C., Antonarakis, S. E., Ro-Lien, T., Lo, W. H. Y., Kazazian, H. H., Jr. The same 'TATA' box beta-thalassemia mutation in Chinese and U.S. blacks: another example of independent origins of mutation. Hum. Genet. 74: 162-164, 1986. [PubMed: 3021607, related citations] [Full Text]

  485. Huang, S., Zhou, X., Zhu, H., Ren, Z., Zeng, Y. Detection of beta-thalassemia mutations in the Chinese using amplified DNA from dried blood specimens. Hum. Genet. 84: 129-131, 1990. [PubMed: 2298448, related citations] [Full Text]

  486. Hubbard, M., Winton, E. F., Lindeman, J. G., Dessauer, P. L., Wilson, J. B., Wrightstone, R. N., Huisman, T. H. J. Hemoglobin Atlanta (beta 75 leu-to-pro): an unstable variant found in several members of a Caucasian family. Biochim. Biophys. Acta 386: 538-541, 1975. [PubMed: 1138885, related citations] [Full Text]

  487. Huehns, E. R., Hecht, F., Yoshida, A., Stamatoyannopoulos, G., Hartman, J., Motulsky, A. G. Hemoglobin-Seattle (beta 76 glu): an unstable hemoglobin causing chronic hemolytic anemia. Blood 36: 209-218, 1970. [PubMed: 5427455, related citations]

  488. Huisman, T. H. J. (ed.). The beta- and delta-thalassemia repository. Hemoglobin 16: 237-258, 1992. [PubMed: 1517101, related citations] [Full Text]

  489. Huisman, T. H. J., Brown, A. K., Efremov, G. D., Wilson, J. B., Reynolds, C. A., Uy, R., Smith, L. L. Hemoglobin Savannah (beta 6 (24) beta-glycine to valine): an unstable variant causing anemia with inclusion bodies. J. Clin. Invest. 50: 650-659, 1971. [PubMed: 5545125, related citations] [Full Text]

  490. Huisman, T. H. J., Carver, M.-F. H., Efremov, G. P. A Syllabus of Human Hemoglobin Variants (1996). Augusta, Ga.: The Sickle Cell Anemia Foundation 1996.

  491. Huisman, T. H. J., Horton, B., Bridges, M. T., Betke, K., Hitzig, W. H. A new abnormal human hemoglobin: hemoglobin-Zurich. Clin. Chim. Acta 6: 347-355, 1960.

  492. Huisman, T. H. J., Sydenstricker, V. P. Haematology: difference in gross structure of two electrophoretically identical 'minor' hemoglobin components. Nature 193: 489-491, 1962. [PubMed: 14449876, related citations] [Full Text]

  493. Huisman, T. H. J., Wilson, J. B., Kutlar, A., Yang, K.-G., Chen, S.-S., Webber, B. B., Altay, C., Martinez, A. V. Hb J-Antakya or beta65 (E9) lys-to-met in a Turkish family and Hb Complutense or beta127 (H5) gln-to-glu in a Spanish family; correction of a previously published identification. Biochim. Biophys. Acta 871: 229-231, 1986. [PubMed: 3707969, related citations] [Full Text]

  494. Huisman, T. H. J. Beta-thalassemia repository. Hemoglobin 14: 661-675, 1990. [PubMed: 2101841, related citations]

  495. Hull, D., Winter, P. C., McHale, C. M., Lappin, T. R. J., Mayne, E. E. Familial hemolytic anemia due to Hb Sabine (beta-91(F7)leu-to-pro) identified by polymerase chain reaction. Hemoglobin 22: 263-266, 1998. [PubMed: 9629500, related citations] [Full Text]

  496. Hunt, J. A., Ingram, V. M. A terminal peptide sequence of human haemoglobin? Nature 184: 640-641, 1959.

  497. Hunt, J. A., Ingram, V. M. Abnormal human haemoglobins. VI. The chemical difference between hemoglobin A and E. Biochim. Biophys. Acta 49: 520-536, 1961. [PubMed: 13716853, related citations] [Full Text]

  498. Husquinet, H., Parent, M. T., Schoos-Barbette, S., Dodinval-Versie, J., Lambotte, C., Galacteros, F. Hemoglobin D-Los Angeles (beta 121 (GH4) glu-to-gln) in the province of Liege, Belgium. Hemoglobin 10: 587-592, 1986. [PubMed: 3557993, related citations] [Full Text]

  499. Hutchison, H. E., Pinkerton, P. H., Waters, P., Douglas, A. S., Lehmann, H., Beale, D. Hereditary Heinz-body anaemia, thrombocytopenia, and haemoglobinopathy (Hb Koln) in a Glasgow family. Brit. Med. J. 2: 1099-1103, 1964. [PubMed: 14198723, related citations] [Full Text]

  500. Hutt, P. J., Pisciotta, A. V., Fairbanks, V. F., Thibodeau, S. N., Green, M. M. DNA sequence analysis proves Hb M-Milwaukee-2 is due to beta-globin gene codon 92 (CAC-to-TAC), the presumed mutation of Hb M-Hyde Park and Hb M-Akita. Hemoglobin 22: 1-10, 1998. [PubMed: 9494043, related citations] [Full Text]

  501. Hyde, R. D., Hall, M. D., Wiltshire, B. G., Lehmann, H. Haemoglobin Southampton, beta 106 (G8) leu to pro: an unstable variant producing severe haemolysis. Lancet 300: 1170-1172, 1972. Note: Originally Volume II. [PubMed: 4117593, related citations] [Full Text]

  502. Idelson, L. I., Didkowsky, N. A., Casey, R., Lorkin, P. A., Lehmann, H. New unstable haemoglobin (Hb Moscva, beta 24 (B6) gly-to-asp) found in the U.S.S.R. Nature 249: 768-770, 1974. [PubMed: 4525423, related citations] [Full Text]

  503. Idelson, L. I., Didkowsky, N. A., Casey, R., Lorkin, P. A., Lehmann, H. Structure and function of haemoglobin Tacoma (beta 30 arg-to-ser) found in a second family. Acta Haemat. 52: 303-311, 1974. [PubMed: 4217534, related citations] [Full Text]

  504. Igarashi, Y., Matsuzaki, S., Kanou, N., Inami, S., Nakamura, T., Kasai, K., Fushitani, K. The first case of Hb E-Saskatoon [alpha(2)-beta(2)22(B4)glu-to-lys] in a Japanese male in Asia. Hemoglobin 19: 403-406, 1995. [PubMed: 8718699, related citations] [Full Text]

  505. Ikkala, E., Koskela, J., Pikkarainen, P., Rahiala, I.-L., El-Hazmi, M. A. F., Nagai, K., Lang, A., Helmann, H. Hb Helsinki: a variant with a high oxygen affinity and a substitution at a 2,3-DPG binding site (beta 82 (EF6) lys-to-met). Acta Haemat. 56: 257-275, 1976. [PubMed: 826083, related citations] [Full Text]

  506. Imai, K., Morimoto, H., Kotani, M., Shibata, S., Miyaji, T., Mastutomo, K. Studies on the function of abnormal hemoglobins. II. Oxygen equilibrium of abnormal hemoglobins: Shimonoseki, Ube II, Hikari, Gifu and Agenogi. Biochim. Biophys. Acta 200: 197-202, 1970. [PubMed: 5416123, related citations] [Full Text]

  507. Imai, K., Yoshioka, Y., Tyuma, I., Hirano, M. Functional abnormalities of hemoglobin Toyoake (142 (H20)beta, ala-to-pro). Biochim. Biophys. Acta 668: 1-15, 1981. [PubMed: 7236701, related citations] [Full Text]

  508. Imamura, T., Fujita, S., Ohta, Y., Hanada, M., Yanase, T. Hemoglobin Yoshizuka (G10(108) beta asparagine to aspartic acid): a new variant with a reduced oxygen affinity from a Japanese family. J. Clin. Invest. 48: 2341-2348, 1969. [PubMed: 5355345, related citations] [Full Text]

  509. Imamura, T., Riggs, A. Identification of hemoglobin Oak Ridge with hemoglobin D Punjab (Los Angeles). Biochem. Genet. 7: 127-130, 1972. [PubMed: 5050915, related citations] [Full Text]

  510. Indrak, K., Wiedermann, B. F., Batek, F., Wilson, J. B., Webber, B. B., Kutlar, A., Huisman, T. H. J. Hb Olomouc or beta86 (F2) ala-to-asp, a new high oxygen affinity variant. Hemoglobin 11: 151-155, 1987. [PubMed: 3623975, related citations] [Full Text]

  511. Ingle, J., Adewoye, A., Dewan, R., Okoli, M., Rollins, L., Eung, S. H., Luo, H., Chui, D. H. K., Steinberg, M. H. Hb Hope [beta-136(H14)gly-to-asp (GGT-to-GAT)]: interactions with Hb S [beta-6(A3)glu-to-val (GAG-to-GTG)], other variant hemoglobins and thalassemia. Hemoglobin 28: 277-285, 2004. [PubMed: 15658184, related citations] [Full Text]

  512. Ingram, V. M. A specific chemical difference between the globins of normal human and sickle-cell anemia haemoglobin. Nature 178: 792-794, 1956. [PubMed: 13369537, related citations] [Full Text]

  513. Ingram, V. M. Gene mutations in human haemoglobin: the chemical difference between normal and sickle cell haemoglobin. Nature 180: 326-328, 1957. [PubMed: 13464827, related citations] [Full Text]

  514. Ingram, V. M. Abnormal human haemoglobin. III. The chemical difference between normal and sickle cell haemoglobins. Biochim. Biophys. Acta 36: 402-411, 1959. [PubMed: 13852872, related citations] [Full Text]

  515. Itano, H. A., Neel, J. V. A new inherited abnormality of human hemoglobin. Proc. Nat. Acad. Sci. 36: 613-617, 1950. [PubMed: 14808148, related citations] [Full Text]

  516. Iuchi, I., Hidaka, K., Harano, T., Ueda, S., Shibata, S., Shimasaki, S., Mizushima, J., Kubo, N., Miyake, T., Uchida, T. Hemoglobin Takamatsu (beta120 (GH 3) lys-to-gln): a new abnormal hemoglobin detected in three unrelated families in the Takamatsu area of Shikoku. Hemoglobin 4: 165-176, 1980. [PubMed: 7390862, related citations] [Full Text]

  517. Iuchi, I., Shimasaki, S., Hidaka, K., Ueda, S., Harano, T., Shibata, S., Mizushima, J., Ohnishi, Y. Hemoglobin J Bangkok (beta56(D7)gly-to-asp): a hemoglobin variant discovered by the hemoglobinopathy survey in Takamatsu district. Hemoglobin 5: 199-204, 1981. [PubMed: 7216820, related citations] [Full Text]

  518. Iuchi, I., Ueda, S., Hidaka, K., Shibata, S. Hemoglobin Hoshida (beta 43 (CD-2) glu-to-gln), a new hemoglobin variant discovered in Japan. Hemoglobin 2: 235-247, 1978. [PubMed: 701082, related citations] [Full Text]

  519. Ivaldi, G., David, O., Baffico, M., Leone, D., Baldi, M., Parodi, M. I., Scime-Degani, V., Piga, A., Scagni, P., Rabino-Massa, E., Ricco, G. Hb Trento: an elongated C-terminal beta chain due to a new frameshift mutation [beta-144 (-A)]. Hemoglobin 27: 15-25, 2003. [PubMed: 12603089, related citations] [Full Text]

  520. Ivaldi, G., David, O., Paradossi, V., Baffico, M., Degani, V. S., Leone, D., Baldi, M., Parodi, M. I., Bernardi, P., Ricco, G. Hb Bologna-St. Orsola (beta-146(HC3)his-to-tyr): a new high oxygen affinity variant with halved Bohr effect and highly reduced reactivity towards 2,3-diphosphoglycerate. Hemoglobin 23: 353-359, 1999. [PubMed: 10569724, related citations] [Full Text]

  521. Ivaldi, G., Scime-Degani, V., David, O., Baffico, M., Baldi, M., Leone, D., Mazzocco, M., Leone, L., Piga, A., Furlan, E., Ricco, G. A new fast-moving variant causing erythrocytosis and mild hemolysis: Hb Gambara (beta-82(EF6)lys-to-glu). Hemoglobin 21: 345-361, 1997. [PubMed: 9255613, related citations] [Full Text]

  522. Jackson, J. M., Way, B. J., Woodliff, H. J. A west Australian family with a haemolytic disorder associated with haemoglobin Koln. Brit. J. Haemat. 13: 474-481, 1967. [PubMed: 6029950, related citations] [Full Text]

  523. Jackson, J. M., Yates, A., Huehns, E. R. Haemoglobin Perth: beta 32 (B14) leu-to-pro, an unstable haemoglobin causing haemolysis. Brit. J. Haemat. 25: 607-610, 1973. [PubMed: 4127713, related citations] [Full Text]

  524. Jacquette, A., Le Roux, G., Lacombe, C., Goossens, M., Pissard, S. Compound heterozygosity for two new mutations in the beta-globin gene [codon 9 (+TA) and polyadenylation site (AATAAA-AAAAAA)] leads to thalassemia intermedia in a Tunisian patient. Hemoglobin 28: 243-248, 2004. [PubMed: 15481893, related citations] [Full Text]

  525. Jankovic, L., Dimovski, A. J., Sukarova, E., Juricic, D., Efremov, G. D. A new mutation in the beta-globin gene (IVS II-850 G-C) found in a Yugoslavian beta-thalassemia heterozygote. Haematologica 77: 119-121, 1992. [PubMed: 1398296, related citations]

  526. Jankovic, L., Efremov, G. D., Josifovska, O., Juricic, D., Stoming, T. A., Kutlar, A., Huisman, T. H. J. An initiation codon mutation as a cause of a beta-thalassemia. Hemoglobin 14: 169-176, 1990. [PubMed: 2272840, related citations] [Full Text]

  527. Jankovic, L., Efremov, G. D., Petkov, G., Kattamis, C., George, E., Yang, K.-G., Stoming, T. A., Huisman, T. H. J. Three novel mutations leading to beta-thalassemia. (Abstract) 31st Annual Meeting of the American Society of Hematology, Atlanta, December 1989.

  528. Jeffreys, A. J., Flavell, R. A. The rabbit beta-globin gene contains a large insert in the coding sequence. Cell 12: 1097-1108, 1977. [PubMed: 597859, related citations] [Full Text]

  529. Jen, P. C., Chen, L. C., Chen, P. F., Wong, Y., Chen, L. F., Guo, Y. Y., Chang, F. Q., Chow, Y. C., Chiu, Y. Hemoglobin Quin-Hai, beta78 (EF2) leu-to-arg, a new abnormal hemoglobin found in Guangdong, China. Hemoglobin 7: 407-412, 1983. [PubMed: 6629822, related citations] [Full Text]

  530. Jensen, M., Oski, F. A., Nathan, D. G., Bunn, H. F. Hemoglobin Syracuse (beta 143(H21) his-to-pro): a new high-affinity variant detected by special electrophoretic methods--observations on auto-oxidation of normal and variant hemoglobins. J. Clin. Invest. 55: 469-477, 1975. [PubMed: 234980, related citations] [Full Text]

  531. Jeppsson, J. O., Kallman, L., Lindgren, G., Fagerstam, L. G. Hb Linkoping (beta36 pro-to-thr): a new hemoglobin mutant characterized by reversed-phase high performance liquid chromatography. J. Chromatogr. 297: 31-36, 1984. [PubMed: 6548480, related citations] [Full Text]

  532. Johnson, C. S., Moyes, D., Schroeder, W. A., Shelton, J. B., Shelton, J. R., Beutler, E. Hemoglobin Pasadena, beta75(E19) leu-to-arg: identification by high performance liquid chromatography of a new unstable variant with increased oxygen affinity. Biochim. Biophys. Acta 623: 360-367, 1980. [PubMed: 7397219, related citations] [Full Text]

  533. Johnson, M. H., Jue, D. L., Patchen, L. C., Hartwig, E. C., Jr., Schneider, N. J., Moo-Penn, W. F. Hemoglobin Tampa: beta79 (EF3) aspartic acid-to-tyrosine. Biochim. Biophys. Acta 623: 119-123, 1980. [PubMed: 7378467, related citations] [Full Text]

  534. Jones, R. T., Brimhall, B., Gray, G. Hemoglobin British Columbia (beta 101 glu-to-lys), a new variant with high oxygen affinity. Hemoglobin 1: 171-182, 1977. [PubMed: 1052179, related citations] [Full Text]

  535. Jones, R. T., Brimhall, B., Huehns, E. R., Motulsky, A. G. Structural characterization of hemoglobin N (Seattle): beta 61 lys-to-glu. Biochim. Biophys. Acta 154: 278-283, 1968. [PubMed: 5637049, related citations] [Full Text]

  536. Jones, R. T., Brimhall, B., Huisman, T. H. J., Kleihauer, E., Betke, K. Hemoglobin Freiburg: abnormal hemoglobin due to deletion of a single amino acid residue. Science 154: 1024-1027, 1966. [PubMed: 5919752, related citations] [Full Text]

  537. Jones, R. T., Brimhall, B., Pootrakul, S., Gray, G. Hemoglobin Vancouver (beta 73 (E17) asp-to-tyr): its structure and function. J. Molec. Evol. 9: 37-44, 1976. [PubMed: 1018330, related citations] [Full Text]

  538. Jones, R. T., Grimes, A. J., Carrell, R. W., Lehmann, H. Koln haemoglobinopathy: further data and a comparison with other hereditary Heinz body anaemias. Brit. J. Haemat. 13: 394-408, 1967. [PubMed: 6067323, related citations] [Full Text]

  539. Jones, R. T., Head, C., Shih, M. F.-C., Shih, D. T.-B., Dana, B., Jones, M. B., Koler, R. D. Hemoglobin Linkoping (beta36 (C2) pro-to-thr) in a large Finnish family from Astoria, Oregon, USA. Hemoglobin 10: 455-467, 1986. [PubMed: 3096913, related citations] [Full Text]

  540. Jones, R. T., Koler, R. D., Duerst, M. L., Dhindsa, D. S. Hemoglobin Willamette (alpha-2 beta-2 51 pro-to-arg (D2)): a new abnormal human hemoglobin. Hemoglobin 1: 45-57, 1976. [PubMed: 1052170, related citations] [Full Text]

  541. Jones, R. T., Koler, R. D., Duerst, M., Stocklen, Z. Hemoglobin Casper (gamma 8 beta 106 leu-to-pro): further evidence that hemoglobin mutations are not random. In: Brewer, G. J.: Hemoglobin and Red Cell Structure and Function. Proc. 2nd Int. Conf. on Red Cell Metabolism and Functions. New York: Plenum Press (pub.) 1973.

  542. Jones, R. T., Osgood, E. E., Brimhall, B., Koler, R. D. Hemoglobin Yakima. I. Clinical and biochemical studies. J. Clin. Invest. 46: 1840-1847, 1967. [PubMed: 6061751, related citations] [Full Text]

  543. Jones, R. T., Saiontz, H. I., Head, C., Shih, D. T. B., Fairbanks, V. F. Hb Johnstown [beta109(G11)val-to-leu]: a new electrophoretically silent variant that causes erythrocytosis. Hemoglobin 14: 147-156, 1990. [PubMed: 2272838, related citations] [Full Text]

  544. Josephson, A. M., Weinstein, H. G., Yakulis, V. J., Singer, L., Heller, P. A new variant of hemoglobin M disease. Hemoglobin M (Chicago). J. Lab. Clin. Med. 59: 918-925, 1962. [PubMed: 14452533, related citations]

  545. Juricic, D., Ruzdic, I., Beer, Z., Efremov, G. D., Casey, R., Lehmann, H. Hemoglobin Leiden (beta6 or 7 (A3 or A4) glu-to-0) in a Yugoslavian woman arisen by a new mutation. Hemoglobin 7: 271-277, 1983. [PubMed: 6874375, related citations] [Full Text]

  546. Kagimoto, T., Morino, Y., Kishimoto, S. A new hemoglobin variant, hemoglobin Yatsushiro (beta 60 val-to-leu). Biochim. Biophys. Acta 532: 195-198, 1978. [PubMed: 620052, related citations] [Full Text]

  547. Kalberer, C. P., Pawliuk, R., Imren, S., Bachelot, T., Takekoshi, K. J., Fabry, M., Eaves, C. J., London, I. M., Humphries, R. K., Leboulch, P. Preselection of retrovirally transduced bone marrow avoids subsequent stem cell gene silencing and age-dependent extinction of expression of human beta-globin in engrafted mice. Proc. Nat. Acad. Sci. 97: 5411-5415, 2000. [PubMed: 10792053, images, related citations] [Full Text]

  548. Kamel, K. A., Hoerman, K., Awny, A. Y. Ethnological significance of hemoglobin beta (121 lys). Am. J. Phys. Anthrop. 26: 107-108, 1967. [PubMed: 5633723, related citations] [Full Text]

  549. Kamel, K. A., Hoerman, K. C., Awny, A. Y. 'Hemoglobin alpha2beta2-121lys:' chemical identification in an Egyptian family. Science 156: 397-398, 1967. [PubMed: 5609824, related citations] [Full Text]

  550. Kamel, K., El-Najjar, A., Webber, B. B., Chen, S. S., Wilson, J. B., Kutlar, A., Huisman, T. H. J. Hb Doha or beta(X-N-Met-1(NA1)val-to-glu); a new beta-chain abnormal hemoglobin observed in a Qatari female. Biochim. Biophys. Acta 831: 257-260, 1985. [PubMed: 3840039, related citations] [Full Text]

  551. Kan, Y. W., Dozy, A. M., Trecartin, R., Todd, D. Identification of a nondeletion defect in alpha-thalassemia. New Eng. J. Med. 297: 1081-1084, 1977. [PubMed: 909565, related citations] [Full Text]

  552. Kan, Y. W., Dozy, A. M. Antenatal diagnosis of sickle-cell anaemia by DNA analysis of amniotic-fluid cells. Lancet 312: 910-912, 1978. Note: Originally Volume II. [PubMed: 81926, related citations] [Full Text]

  553. Kan, Y. W., Dozy, A. M. The evolution of the hemoglobin S and C genes in the world population. (Abstract) Clin. Res. 27: 274A, 1979.

  554. Kan, Y. W., Golbus, M. S., Trecartin, R. Prenatal diagnosis of homozygous beta-thalassaemia. Lancet 2: 790-791, 1975. [PubMed: 78154, related citations]

  555. Kan, Y. W., Holland, J. P., Dozy, A. M., Charache, S., Kazazian, H., Jr. Deletion of the beta globin structural gene in hereditary persistence of fetal hemoglobin. Nature 258: 162-163, 1975. [PubMed: 1186896, related citations] [Full Text]

  556. Kan, Y. W., Holland, J. P., Dozy, A. M., Varmus, H. E. Demonstration of non-functional beta globin mRNA in homozygous beta-0 thalassemia. Proc. Nat. Acad. Sci. 72: 5140-5144, 1975. [PubMed: 1061099, related citations] [Full Text]

  557. Kan, Y. W., Lee, K. Y., Forbetta, M., Angius, A., Cao, A. Polymorphism of DNA sequence in the beta-globin gene region: application to prenatal diagnosis of beta-zero-thalassemia in Sardinia. New Eng. J. Med. 302: 185-188, 1980. [PubMed: 6927915, related citations] [Full Text]

  558. Kaplan, F., Kokotsis, G., DeBraekeleer, M., Morgan, K., Scriver, C. R. Beta-thalassemia genes in French-Canadians: haplotype and mutation analysis of Portneuf chromosomes. Am. J. Hum. Genet. 46: 126-132, 1990. [PubMed: 1967205, related citations]

  559. Kattamis, A. C., Kelly, K. M., Ohene-Frempong, K., Reilly, M. P., Keller, M., Cubeddu, R., Adachi, K., Surrey, S., Fortina, P. Hb Osler [beta-145(HC2)tyr-to-asp] results from posttranslational modification. Hemoglobin 21: 109-120, 1997. [PubMed: 9101280, related citations] [Full Text]

  560. Kaufman, R. E., Kretschmer, P. J., Adams, J. W., Coon, H. C., Anderson, W. F., Nienhuis, A. W. Cloning and characterization of DNA sequences surrounding the human gamma-, delta-, and beta-globin genes. Proc. Nat. Acad. Sci. 77: 4229-4233, 1980. [PubMed: 6254016, related citations] [Full Text]

  561. Kaufman, S., Leiba, H., Clejan, L., Wallis, K., Lorkin, P. A., Lehmann, H. Hemoglobin G-Szuhu, beta-80 asn-to-lys, in the homozygous state in the patient with abetalipoproteinemia. Hum. Hered. 25: 60-68, 1975. [PubMed: 1150295, related citations] [Full Text]

  562. Kavanaugh, J. S., Rogers, P. H., Case, D. A., Arnone, A. High-resolution x-ray study of deoxyhemoglobin Rothschild 37-beta trp-to-arg: a mutation that creates an intersubunit chloride-binding site. Biochemistry 31: 4111-4121, 1992. [PubMed: 1567857, related citations] [Full Text]

  563. Kawata, R., Ohba, Y., Fujisawa, K., Miyaji, T., Tani, Y., Iwasaki, M. Further examples of Hb Takamatsu in Japan. Hemoglobin 13: 89-91, 1989. [PubMed: 2703369, related citations] [Full Text]

  564. Kawata, R., Ohba, Y., Yamamoto, K., Miyaji, T., Makita, R., Ohga, K., Watanabe, S., Miwa, S. Hyperunstable hemoglobin Koriyama: anti-Hb Gun Hill insertion of five residues in the beta chain. Hemoglobin 12: 311-321, 1988. [PubMed: 3170234, related citations] [Full Text]

  565. Kazazian, H. H., Jr., Boehm, C. D. Molecular basis and prenatal diagnosis of beta-thalassemia. Blood 72: 1107-1116, 1988. [PubMed: 3048433, related citations]

  566. Kazazian, H. H., Jr., Dowling, C. E., Hurwitz, R. L., Coleman, M., Adams, J. G., III. Thalassemia mutations in exon 3 of the beta-globin gene often cause a dominant form of thalassemia and show no predilection for malarial-endemic regions of the world. (Abstract) Am. J. Hum. Genet. 45: A242, 1989.

  567. Kazazian, H. H., Jr., Dowling, C. E., Hurwitz, R. L., Coleman, M., Stopeck, A., Adams, J. G., III. Dominant thalassemia-like phenotypes associated with mutations in exon 3 of the beta-globin gene. Blood 79: 3014-3018, 1992. [PubMed: 1586746, related citations]

  568. Kazazian, H. H., Jr., Fearon, E. R., Waber, P. G., Lee, J. I., Antonarakis, S. E., Orkin, S. H., Vanin, E. F., Heathorn, P. S., Grosveld, F. G., Buchanan, G. R. Gamma-delta-beta thalassemia: deletion of the entire beta-globin gene cluster. (Abstract) Blood 60: 54A, 1982.

  569. Kazazian, H. H., Jr., Orkin, S. H., Antonarakis, S. E., Sexton, J. P., Boehm, C. D., Goff, S. C., Waber, P. G. Molecular characterization of seven beta-thalassemia mutations in Asian Indians. EMBO J. 3: 593-596, 1984. [PubMed: 6714226, related citations] [Full Text]

  570. Kazazian, H. H., Jr., Orkin, S. H., Boehm, C. D., Goff, S. C., Wong, C., Dowling, C. E., Newburger, P. E., Knowlton, P. G., Brown, V., Donis-Keller, H. Characterization of a spontaneous mutation to a beta-thalassemia allele. Am. J. Hum. Genet. 38: 860-867, 1986. [PubMed: 3014870, related citations]

  571. Kazazian, H. H., Jr., Orkin, S. H., Boehm, C. D., Sexton, J. P., Antonarakis, S. E. Beta-thalassemia due to deletion of the nucleotide which is substituted in sickle cell anemia. Am. J. Hum. Genet. 35: 1028-1033, 1983. [PubMed: 6310991, related citations]

  572. Kazazian, H. H., Jr., Waber, P. G., Boehm, C. D., Lee, J. I., Antonarakis, S. E., Fairbanks, V. F. Hemoglobin E in Europeans: further evidence for multiple origins of the beta-E-globin gene. Am. J. Hum. Genet. 36: 212-217, 1984. [PubMed: 6198908, related citations]

  573. Kazazian, H. H., Jr. Personal Communication. Baltimore, Md. 1982.

  574. Kazazian, H. H., Jr. Personal Communication. Baltimore, Md. 1989.

  575. Kazazian, H. H., Jr. Personal Communication. Baltimore, Md. 1990.

  576. Kazazian, H. H., Jr. Personal Communication. Baltimore, Md. 1992.

  577. Keclard, L., Campier, A., Merault, G., Auperin, A., Riou, J., Rosa, J., Galacteros, F. Hemoglobin Nevers [beta130(H8)tyr-to-ser]: a new silent variant found in France. Hemoglobin 14: 103-107, 1990. [PubMed: 2384309, related citations] [Full Text]

  578. Keeling, M. M., Bertolone, S. J., Baysal, E., Gu, Y.-C., Cepreganova, B., Wilson, J. B., Huisman, T. H. J. Hb Mizuho or beta68(E12)leu-to-pro in a Caucasian boy with high levels of Hb F: identification by sequencing of amplified DNA. Hemoglobin 15: 477-485, 1991. [PubMed: 1726094, related citations] [Full Text]

  579. Keeling, M. M., Ogden, L. L., Wrightstone, R. N., Wilson, J. B., Reynolds, C. A., Kitchens, J. L., Huisman, T. H. J. Hemoglobin Louisville (beta 42 (CD1) phe-to-leu): an unstable variant causing mild hemolytic anemia. J. Clin. Invest. 50: 2395-2402, 1971. [PubMed: 5096522, related citations] [Full Text]

  580. Kendall, A. G., ten Pas, A., Wilson, J. B., Cope, N., Bolch, K., Huisman, T. H. J. Hb Vaasa or beta 39: gln-to-glu, a mildly unstable variant found in a Finnish family. Hemoglobin 1: 292-295, 1977. [PubMed: 893132, related citations] [Full Text]

  581. Kendall, A., Pang, W. Hemoglobin New York associated with alpha-thalassemia. Hum. Hered. 30: 50-53, 1980. [PubMed: 7353889, related citations] [Full Text]

  582. Kendall, A., Young, S., Oune, N., Wiltshire, B., Lehmann, H. The unstable Hb Genova (beta 28 leu-to-pro) in a East African family: family study and the effect of splenectomy. Acta Haemat. 61: 278-282, 1979. [PubMed: 111455, related citations] [Full Text]

  583. Kennedy, C. C., Blundell, G., Lorkin, P. A., Lang, A., Lehmann, H. Hemoglobin Belfast 15(A12) trp-to-arg: a new unstable hemoglobin variant. Brit. Med. J. 4: 324-326, 1974. [PubMed: 4434089, related citations] [Full Text]

  584. Keser, I., Kayisli, O. G., Yesilipek, A., Ozes, O. N., Luleci, G. Hb Anatalya (codons 3-5 (Leu-Thr-Pro-to-Ser-Asp-Ser)): A new unstable variant leading to chronic microcytic anemia and high Hb A2. Hemoglobin 25: 369-373, 2001. [PubMed: 11791869, related citations] [Full Text]

  585. Kiger, L., Kister, J., Groff, P., Kalmes, G., Prome, D., Galacteros, F., Wajcman, H. Hb J-Europa [beta-62(E6)ala-to-asp]: normal oxygen binding properties in a new variant involving a residue located distal to the heme. Hemoglobin 20: 135-140, 1996. [PubMed: 8811317, related citations] [Full Text]

  586. Kim, J. Y., Park, S. S., Jung, H. L., Keum, D. H., Park, H., Chang, Y. H., Lee, Y. J., Cho, H. I. Hb Madrid (beta-115(G17)ala-to-pro) in a Korean family with chronic hemolytic anemia. Hemoglobin 24: 133-138, 2000. [PubMed: 10870884, related citations] [Full Text]

  587. Kim, J. Y., Park, S. S., Yang, S. H., Joo, S.-I., Lee, Y. J., Ra, E. K., Shin, S., Kim, E. C., Cho, H.-I. A Korean family with a dominantly inherited beta-thalassemia due to Hb Durham-N.C./Brescia (beta-114(G16)leu-to-pro). Hemoglobin 25: 79-89, 2001. [PubMed: 11300352, related citations] [Full Text]

  588. Kimura, A., Matsunaga, E., Takihara, Y., Nakamura, T., Takagi, Y. Structural analysis of a beta-thalassemia gene found in Taiwan. J. Biol. Chem. 258: 2748-2749, 1983. [PubMed: 6826539, related citations]

  589. Kimura, A., Ohta, Y., Fukumaki, Y., Takagi, Y. A fusion gene in man: DNA sequence analysis of the abnormal globin gene of hemoglobin Miyada. Biochem. Biophys. Res. Commun. 119: 968-974, 1984. [PubMed: 6324786, related citations] [Full Text]

  590. Kimura, E. M., Jorge, S. B., Ogo, S. H., Cesquini, M., Albuquerque, D. M., Fattori, A., Saad, S. T. O., Costa, F. F., Sonati, M. F. A novel beta-globin variant: Hb Pocos de Caldas (beta-61(E5)lys-to-gln). Hemoglobin 26: 385-388, 2002. [PubMed: 12484633, related citations] [Full Text]

  591. King, M. A. R., Wiltshire, B. G., Lehmann, H., Morimoto, H. An unstable haemoglobin with reduced oxygen affinity: haemoglobin Peterborough, beta 111 (G13) valine to phenylalanine, its interaction with normal haemoglobin and with haemoglobin Lepore. Brit. J. Haemat. 22: 125-134, 1972. [PubMed: 5057941, related citations] [Full Text]

  592. Kinniburgh, A. J., Maquat, L. E., Schedl, T., Rachmilewitz, E., Ross, J. mRNA deficient beta-0-thalassemia results from a single nucleotide deletion. Nucleic Acids Res. 10: 5421-5427, 1982. [PubMed: 6292840, related citations] [Full Text]

  593. Kister, J., Prehu, C., Riou, J., Godart, C., Bardakdjian, J., Prome, D., Galacteros, F., Wajcman, H. Two hemoglobin variants with an alteration of the oxygen-linked chloride binding: Hb Antananarivo [alpha1(NA1)val-to-gly] and Hb Barbizon [beta144(HC1)lys-to-met]. Hemoglobin 23: 21-32, 1999. [PubMed: 10081983, related citations] [Full Text]

  594. Kleckner, H. B., Wilson, J. B., Lindeman, J. G., Stevens, P. D., Naizi, G., Hunter, E., Chen, C. J., Huisman, T. H. J. Hemoglobin Fort Gordon (beta 145 tyr-to-asp), a new high-oxygen-affinity hemoglobin variant. Biochim. Biophys. Acta 400: 343-347, 1975. [PubMed: 1164510, related citations] [Full Text]

  595. Kobayashi, S., Nara, T., Nakano, Y., Fukazawa, H., Kawamura, G., Kitajima, H., Sugita, M., Joh, K., Ohba, Y., Hattori, Y., Miyaji, T. Hemoglobin Burke: an unstable hemoglobin rarely associated with hemolytic episodes. Hemoglobin 10: 661-666, 1986. [PubMed: 3557997, related citations] [Full Text]

  596. Kobayashi, Y., Fukumaki, Y., Komatsu, N., Ohba, Y., Miyaji, T., Miura, Y. A novel globin structural mutant, Showa-Yakushiji (beta-110 leu-to-pro) causing a beta-thalassemia phenotype. Blood 70: 1688-1691, 1987. [PubMed: 2822177, related citations]

  597. Kohen, G., Philippe, N., Godet, J. Polymorphism of the HindI restriction site located 1 kb 5-prime to the human beta-globin gene. Hum. Genet. 62: 121-123, 1982. [PubMed: 6298094, related citations] [Full Text]

  598. Kohne, E., Grosse, H. P., Versmold, H., Kley, H. P., Kleihauer, E. Hb M Erlangen: beta 63 (E7) tyr. Eine neue Mutation mit Haemolyse und Diaphorasemangel. Z. Kinderheilk. 120: 69-78, 1975. [PubMed: 1163074, related citations]

  599. Kohne, E., Kley, H. P., Kleihauer, E. Structural and functional characteristics of the Hb Tubingen: beta 106 (G8) leu-to-gln. FEBS Lett. 64: 443-447, 1976. [PubMed: 1278400, related citations] [Full Text]

  600. Kohne, E., Wendt, F.-K., Kleinhauer, E. Hb M Milwaukee in a German family. Hemoglobin 1: 759-769, 1977. [PubMed: 604314, related citations] [Full Text]

  601. Koler, R. D., Jones, R. T., Bigley, R. H., Litt, M., Lovrien, E., Brooks, R., Lahey, M. E., Fowler, R. Hemoglobin Casper: beta 106 (gamma 8) leu-to-pro: a contemporary mutation. Am. J. Med. 55: 549-558, 1973. [PubMed: 4743351, related citations] [Full Text]

  602. Kollia, P., Gonzalez-Redondo, J. M., Stoming, T. A., Loukopoulos, D., Politis, C., Huisman, T. H. J. Frameshift codon 5 [FSC-5 (-CT)] thalassemia: a novel mutation detected in a Greek patient. Hemoglobin 13: 597-604, 1989. [PubMed: 2606727, related citations] [Full Text]

  603. Konotey-Ahulu, F. I. D., Gallo, E., Lehmann, H., Ringelhann, B. Haemoglobin Korle-Bu (beta 73 aspartic acid to asparagine) showing one of the two amino acid substitutions of haemoglobin C Harlem. J. Med. Genet. 5: 107-111, 1968. [PubMed: 5722880, related citations] [Full Text]

  604. Konotey-Ahulu, F. I. D., Kinderlerer, J. L., Lehmann, H., Ringelhann, B. Haemoglobin Osu-Christiansborg: a new beta-chain variant of haemoglobin A (beta 52(D3) aspartic acid-to-asparagine) in combination with haemoglobin S. J. Med. Genet. 8: 302-305, 1971. [PubMed: 5097135, related citations] [Full Text]

  605. Koop, B. F., Goodman, M., Xu, P., Chan, K., Slightom, J. L. Primate eta-globin DNA sequences and man's place among the great apes. Nature 319: 234-238, 1986. [PubMed: 3945312, related citations] [Full Text]

  606. Kosugi, H., Weinstein, A. S., Kikugawa, K., Asakura, T. Characterization and properties of Hb York (beta146 his-to-pro). Hemoglobin 7: 205-226, 1983. [PubMed: 6874372, related citations] [Full Text]

  607. Krawczak, M., Ball, E. V., Fenton, I., Stenson, P. D., Abeysinghe, S., Thomas, N., Cooper, D. N. Human gene mutation database--a biomedical information and research resource. Hum. Mutat. 15: 45-51, 2000. [PubMed: 10612821, related citations] [Full Text]

  608. Krawczak, M., Reiss, J., Cooper, D. N. The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences. Hum. Genet. 90: 41-54, 1992. [PubMed: 1427786, related citations] [Full Text]

  609. Krishnan, K., Martinez, F., Cooney, K., Jones, R. T., Shih, D. T., Dabich, L. Co-inheritance of a low oxygen affinity hemoglobin, Hb Washtenaw, beta11 (A8) val-to-phe and primary pulmonary hypertension in a Hungarian-American kindred. (Abstract) Blood 82 (suppl. 1): 471a, 1993.

  610. Krishnan, K., Martinez, F., Wille, R. T., Jones, R. T., Shih, D. T., Head, C., Fairbanks, V. F., Dabich, L. Hb Washtenaw (beta-11(A8) val-to-phe): an electrophoretically silent, unstable, low oxygen affinity variant associated with anemia and chronic cyanosis. Hemoglobin 18: 285-295, 1994. [PubMed: 7852083, related citations] [Full Text]

  611. Kuis-Reerink, J. D., Jonxis, J. H., Niazi, G. A., Wilson, J. B., Bolch, K. C., Gravely, M., Huisman, T. H. Hb-Volga or alpha-2 beta-2 27(B9) ala replaced by asp: an unstable hemoglobin variant in three generations of a Dutch family. Biochim. Biophys. Acta 439: 63-69, 1976. [PubMed: 952960, related citations] [Full Text]

  612. Kulozik, A. E., Wainscoat, J. S., Serjeant, G. R., Kar, B. C., Al-Awamy, B., Essan, G. J. F., Falusi, A. G., Haque, S. K., Hilali, A. M., Kate, S., Ranasinghe, W. A. E. P., Weatherall, D. J. Geographical survey of beta-S-globin gene haplotypes: evidence for an independent Asian origin of the sickle-cell mutation. Am. J. Hum. Genet. 39: 239-244, 1986. [PubMed: 3752087, related citations]

  613. Kulozik, A. E., Yarwood, N., Jones, R. W. The Corfu delta-beta-zero thalassemia: a small deletion acts at a distance to selectively abolish beta globin gene expression. Blood 71: 457-462, 1988. Note: Erratum: 71: 1509 only, 1988. [PubMed: 2827815, related citations]

  614. Kurachi, S., Hermodson, M., Hornung, S., Stamatoyannopoulos, G. Structure of haemoglobin Seattle. Nature N.B. 243: 275-276, 1973. [PubMed: 4515495, related citations] [Full Text]

  615. Kutlar, A., Kutlar, F., Aksoy, M., Gurgey, A., Altay, C., Wilson, J. B., Diaz-Chico, J. C., Hu, H., Huisman, T. H. J. Beta-thalassemia intermedia in two Turkish families is caused by the interaction of Hb Knossos (beta27 (B9) ala-to-ser) and of Hb City of Hope (beta69 (E13) gly-to-ser) with beta-zero-thalassemia. Hemoglobin 13: 7-16, 1989. [PubMed: 2467892, related citations] [Full Text]

  616. Kutlar, F., Felice, A. E., Grech, J. L., Bannister, W. H., Kutlar, A., Wilson, J. B., Webber, B. B., Hu, H., Huisman, T. H. J. The linkage of Hb Valletta (beta-87(F3)thr-to-pro) and Hb F-Malta-I (G-gamma-117(G19)his-to-arg) in the Maltese population. Hum. Genet. 86: 591-594, 1991. [PubMed: 1709134, related citations] [Full Text]

  617. Kwiatkowski, D. P. How malaria has affected the human genome and what human genetics can teach us about malaria. Am. J. Hum. Genet. 77: 171-192, 2005. [PubMed: 16001361, related citations] [Full Text]

  618. Kyrri, A., Felekis, X., Kalogerou, E., Christopoulos, G., Makariou, C., Loizidou, D., Kleanthous, M. Hb Limassol (beta-8(A5)lys-to-asn): a new hemoglobin variant. Hemoglobin 25: 421-424, 2001. [PubMed: 11791876, related citations] [Full Text]

  619. Labie, D., Bernadou, A., Wajcman, H., Bilski-Pasquier, G. A familial observation of hemoglobin Genova (beta 28 (B10) leu-to-pro). A hematological, genetic and biochemical clinical study of a French family. Nouv. Rev. Franc. Hemat. 12: 502-505, 1972. [PubMed: 4264206, related citations]

  620. Labie, D., Rosa, J., Belkhodja, O., Bierme, R. Hemoglobin Toulouse beta66 (E10)lys-to-glu: structure and consequences in molecular pathology. Biochim. Biophys. Acta 236: 201-207, 1971. [PubMed: 5577462, related citations]

  621. Labossiere, A., Hill, J. R., Vella, F. A new B-TP V hemoglobin variant: Hb Edmonton. Clin. Biochem. 4: 114-117, 1971. [PubMed: 5128293, related citations] [Full Text]

  622. Labossiere, A., Vella, F., Hiebert, J., Galbraith, P. Hemoglobin Deer Lodge: beta2 his-to-arg. Clin. Biochem. 5: 46-50, 1972. [PubMed: 5022448, related citations] [Full Text]

  623. Lacan, P., Badens, C., Lena-Russo, D., Merono, F., Thuret, I., Aubry, M., Couprie, N., Francina, A. Hb Aubagne [beta-64(E8)gly-to-ala]: a new unstable beta chain variant found in a French family. Hemoglobin 26: 163-167, 2002. [PubMed: 12144059, related citations] [Full Text]

  624. Lacan, P., Becchi, M., Zanella-Cleon, I., Aubry, M., Ffrench, M., Couprie, N., Francina, A. Two new beta chain variants: Hb Tripoli [beta-26(B8)glu-to-ala] and Hb Tizi-Ouzou [beta-29(B11)gly-to-ser]. Hemoglobin 28: 205-212, 2004. [PubMed: 15481887, related citations] [Full Text]

  625. Lacan, P., Francina, A., Prome, D., Delaunay, J., Galacteros, F., Wajcman, H. Hb Aubenas [beta-26(B8)glu-to-gly]: a new variant normally synthesized, affecting the same codon as in Hb E. Hemoglobin 20: 113-124, 1996. [PubMed: 8811314, related citations] [Full Text]

  626. Lacan, P., Kister, J., Francina, A., Souillet, G., Galacteros, F., Delaunay, J., Wajcman, H. Hemoglobin Debrousse (beta-96-(FG3)leu-to-pro): a new unstable hemoglobin with twofold increased oxygen affinity. Am. J. Hemat. 51: 276-281, 1996. [PubMed: 8602627, related citations] [Full Text]

  627. Lacan, P., Moreau, M., Becchi, M., Zanella-Cleon, I., Aubry, M., Louis, J.-J., Couprie, N., Francina, A. Two new hemoglobin variants: Hb Brem-sur-Mer (beta-9(A6)ser-to-tyr) and Hb Passy (alpha-81(F2)ser-to-pro (alpha-2)). Hemoglobin 29: 69-75, 2005. [PubMed: 15768558, related citations]

  628. Lacombe, C., Arous, N., Pontet, F., Blouquit, Y., Bardakdjian, J., Riou, J., Rousselet, F., Galacteros, F. Hb I-High Wycombe (beta59 (E3) lys-to-glu) in a woman of Malian origin. Hemoglobin 11: 173-176, 1987. [PubMed: 3114176, related citations] [Full Text]

  629. Lacombe, C., Blouquit, Y., Arous, N., Riou, J., Harousseau, J. L., Bardakdjian, J., Milpied, N., Galacteros, F. Hb Potomac (beta101 (G3) glu-to-asp) in a Polish family living in France. Hemoglobin 11: 55-59, 1987. [PubMed: 3583767, related citations] [Full Text]

  630. Lacombe, C., Craescu, C. T., Blouquit, Y., Kister, J., Poyart, C., Delanoe-Garin, J., Arous, N., Bardakdjian, J., Riou, J., Rosa, J., Schaeffer, C., Galacteros, F. Structural and functional studies of hemoglobin Poissy beta56 (D7) gly-to-arg and beta86 ala-to-pro. Europ. J. Biochem. 153: 655-662, 1985. [PubMed: 3841063, related citations] [Full Text]

  631. Lacombe, C., Prome, D., Blouquit, Y., Bardakdjian, J., Arous, N., Mrad, A., Prome, J.-C., Rosa, J. New results of hemoglobin variant structure determinations by fast atom bombardment mass spectrometry. Hemoglobin 14: 529-548, 1990. [PubMed: 2079433, related citations] [Full Text]

  632. Lafferty, J., Ali, M., Matthew, K., Eng, B., Patterson, M., Waye, J. S. Identification of a new high oxygen affinity hemoglobin variant: Hb Aurora [beta-139(H17)asn-to-tyr]. Hemoglobin 19: 335-341, 1995. [PubMed: 8718692, related citations] [Full Text]

  633. Laig, M., Sanguansermsri, T., Wiangnon, S., Hundrieser, J., Pape, M., Flatz, G. The spectrum of beta-thalassemia mutations in northern and northeastern Thailand. Hum. Genet. 84: 47-50, 1989. [PubMed: 2606477, related citations] [Full Text]

  634. Lam, H., Wilson, J. B., Harris, H., Gravely, M., Huisman, T. H. J. Hemoglobin Alamo (beta 19 (B1) asn-to-asp). Hemoglobin 1: 703-706, 1977. [PubMed: 914645, related citations] [Full Text]

  635. Lambotte-Legrand, J., Lambotte-Legrand, C., Ager, J. A., Lehmann, H. L'hemoglobinose P: a propos d'un cas d'association des hemoglobines P et S. Rev. Hemat. 15: 10-18, 1960. [PubMed: 14413637, related citations]

  636. Lanclos, K. D., Patterson, J., Efremov, G. D., Wong, S. C., Villegas, A., Ojwang, P. J., Wilson, J. B., Kutlar, F., Huisman, T. H. J. Characterization of chromosomes with hybrid genes for Hb Lepore-Washington, Hb Lepore-Baltimore, Hb P-Nilotic, and Hb Kenya. Hum. Genet. 77: 40-45, 1987. [PubMed: 2442092, related citations] [Full Text]

  637. Landin, B., Berglund, S., Lindoff, B. Hb Trollhaettan [beta-20 (B2) val-to-glu]--a new haemoglobin variant with increased oxygen affinity causing erythrocytosis. Europ. J. Haemat. 53: 21-25, 1994. [PubMed: 7914875, related citations]

  638. Landin, B., Berglund, S., Wallman, K. Two different mutations in codon 97 of the beta-globin gene cause Hb Malmo in Sweden. Am. J. Hemat. 51: 32-36, 1996. [PubMed: 8571935, related citations] [Full Text]

  639. Landin, B., Frostad, B., Brune, M., Ljung, R. Haemoglobin Koln as de novo mutations in Sweden: diagnosis by PCR and specific enzymatic cleavage. Europ. J. Haemat. 52: 156-161, 1994. [PubMed: 8168595, related citations] [Full Text]

  640. Landin, B., Rudolphi, O., Ek, B. Initiation codon mutation (ATG-ATA) of the beta-globin gene causing beta-thalassemia in a Swedish family. Am. J. Hemat. 48: 158-162, 1995. [PubMed: 7864023, related citations] [Full Text]

  641. Landin, B. Hb Karlskoga or beta21 (B3) asp-to-his: a new slow-moving variant found in Sweden. Hemoglobin 17: 201-208, 1993. [PubMed: 8330972, related citations] [Full Text]

  642. Landman, H., Wilson, J. B., Kutlar, A., Gonzalez Redondo, J. M., Huisman, T. H. J. Hb G-Taipei or beta22 (B4) glu-to-gly in a Chinese family living in the Netherlands. Hemoglobin 11: 169-171, 1987. [PubMed: 3623978, related citations] [Full Text]

  643. Lane, P. A., Rogers, Z. R., Woods, G. M., Wang, W. C., Wilimas, J. A., Miller, S. T., Khakoo, Y., Buchanan, G. R. Fatal pneumococcal septicemia in hemoglobin SC disease. J. Pediat. 124: 859-862, 1994. [PubMed: 8201467, related citations] [Full Text]

  644. Lang, A., Lehmann, H., McCurdy, P. R., Pierce, L. Identification of haemoglobin C Georgetown. Biochim. Biophys. Acta 278: 57-61, 1972. [PubMed: 5069596, related citations] [Full Text]

  645. Langdown, J. V., Williamson, D., Beresford, C. H., Gibb, I., Taylor, R., Deacon-Smith, R. A new beta chain variant, Hb Tyne (beta-5 (A2) pro-to-ser). Hemoglobin 18: 333-336, 1994. [PubMed: 7852088, related citations] [Full Text]

  646. Langdown, J. V., Williamson, D., Knight, C. B., Rubenstein, D., Carrell, R. W. A new doubly substituted sickling haemoglobin: HbS-Oman. Brit. J. Haemat. 71: 443-444, 1989. [PubMed: 2930724, related citations] [Full Text]

  647. Lapoumeroulie, C., Dunda, O., Ducrocq, R., Trabuchet, G., Mony-Lobe, M., Bodo, J. M., Carnevale, P., Labie, D., Elion, J., Krishnamoorthy, R. A novel sickle cell mutation of yet another origin in Africa: the Cameroon type. Hum. Genet. 89: 333-337, 1992. [PubMed: 1376298, related citations] [Full Text]

  648. Lapoumeroulie, C., Pagnier, J., Bank, A., Labie, D., Krishnamoorthy, R. Beta-thalassemia due to a novel mutation in IVS-1 sequence donor site consensus sequence creating a restriction site. Biochem. Biophys. Res. Commun. 139: 709-713, 1986. [PubMed: 3021139, related citations] [Full Text]

  649. Lau, Y.-L., Chan, L.-C., Chan, Y.-Y. A., Ha, S.-Y., Yeung, C.-Y., Waye, J. S., Chui, D. H. K. Prevalence and genotypes of alpha- and beta-thalassemia carriers in Hong Kong: implications for population screening. New Eng. J. Med. 336: 1298-1301, 1997. [PubMed: 9113933, related citations] [Full Text]

  650. Lawn, R. M., Efstratiadis, A., O'Connell, C. O., Maniatis, T. The nucleotide sequence of the human beta-globin gene. Cell 21: 647-651, 1980. [PubMed: 6254664, related citations] [Full Text]

  651. Lebo, R. V., Carrano, A. V., Burkhart-Schultz, K., Dozy, A. M., Yu, C.-C., Kan, Y. W. Assignment of human beta-, gamma-, and delta-globin genes to the short arm of chromosome 11 by chromosome sorting and DNA restriction enzyme analysis. Proc. Nat. Acad. Sci. 76: 5804-5808, 1979. [PubMed: 293684, related citations] [Full Text]

  652. Lebo, R. V., Cheung, M.-C., Bruce, B. D., Riccardi, V. M., Kao, F.-T., Kan, Y. W. Mapping parathyroid hormone, beta-globin, insulin, and LDH-A genes within the human chromosome 11 short arm by spot blotting sorted chromosomes. Hum. Genet. 69: 316-320, 1985. [PubMed: 2985490, related citations] [Full Text]

  653. Lebo, R. V., Kan, Y. W., Cheung, M. C., Cordell, B., Goodman, H. M., Law, M. L., Jones, C., Kao, F. T. Assignment of the human insulin gene to chromosome 11 band p11 and linkage analysis with the beta-globin locus. (Abstract) Am. J. Hum. Genet. 33: 150A, 1981.

  654. Lehmann, H., Beale, D., Boi-Doku, F. S. Haemoglobin G (Accra). Nature 203: 363-365, 1964. [PubMed: 14197371, related citations] [Full Text]

  655. Lehmann, H., Carrell, R. W. Variations in the structure of human haemoglobins: with particular reference to the unstable haemoglobins. Brit. Med. Bull. 25: 14-23, 1969. [PubMed: 5782754, related citations] [Full Text]

  656. Lehmann, H., Charlesworth, D. Observations on haemoglobin P (Congo type). Biochem. J. 119: 43P, 1970. [PubMed: 5492814, related citations] [Full Text]

  657. Lehmann, H. Haemolyse aufgrund instabiler Haemoglobine. In: Nowicki, L.; Martin, H.; Schubert, J. C. F. (eds.): Haemolyse-haemolytische Erkrankungen. Munich: J. F. Lehmanns Verlag (pub.) 1973.

  658. Lehmann, H. Hemoglobin Coventry, a beta-delta chain? In: Brewer, G. J. (ed.): The Red Cell. New York: Alan R. Liss (pub.) 1978. Pp. 83-89.

  659. Lena-Russo, D., Orsini, A., Vovan, L., Bardakdjian-Michau, J., Lacombe, C., Blouquit, Y., Craescu, C. T., Galacteros, F. Hemoglobin N-Timone (beta8(A5)lys-to-glu): a new fast-moving variant with normal stability and oxygen affinity. Hemoglobin 13: 743-747, 1989. [PubMed: 2634671, related citations] [Full Text]

  660. Lewis, J., Yang, B., Kim, R., Sierakowska, H., Kole, R., Smithies, O., Maeda, N. A common human beta globin splicing mutation modeled in mice. Blood 91: 2152-2156, 1998. [PubMed: 9490703, related citations]

  661. Li, H. J., Liu, D. X., Li, L., Liu, Z. G., Lo, S. L., Zhao, J., Han, X. P., Yu, W. Z. A note about the incidence and origin of Hb D-Punjab in Xinjiang, People's Republic of China. Hemoglobin 10: 667-671, 1986. [PubMed: 3557998, related citations] [Full Text]

  662. Li, H. J., Zhao, X. N., Li, H. W., Li, L., Liang, K. X., Wang, R. P., Chang, T. T., Wilson, J. B., Webber, B. B., Huisman, T. H. J. A new slow-moving hemoglobin variant Hb Tianshui or beta39(C5)gln-to-arg, observed in a Chinese family living in Gansu. Hemoglobin 14: 569-570, 1990. [PubMed: 2079437, related citations] [Full Text]

  663. Li, H., Zhao, X., Qin, F., Li, H., Li, L., He, X., Chang, X., Li, Z., Liang, K., Xing, F., Chang, W., Wong, R., Yang, I., Li, F., Zhang, T., Tian, R., Webber, B. B., Wilson, J. B., Huisman, T. H. J. Abnormal hemoglobins in the Silk Road region of China. Hum. Genet. 86: 231-235, 1990. [PubMed: 2265836, related citations] [Full Text]

  664. Li, W., Hattori, Y., Ohba, Y., Okayama, N., Lin, W. S., Long, G. F., Yamashiro, Y., Yamamoto, K., Yamamoto, K. Another example of the beta-thalassemia mutation, IVS-I(-2) or codon 30 (A-G), found in a Chinese family. Hemoglobin 22: 377-381, 1998. [PubMed: 9730368, related citations] [Full Text]

  665. Lie-Injo, L. E., Lopez, C. G., Eapen, J. S., Eravelly, J., Wiltshire, B. G., Lehmann, H. Unstable haemoglobin Koln disease in members of a Malay family. J. Med. Genet. 9: 340-343, 1972. [PubMed: 5079107, related citations] [Full Text]

  666. Lin, C. C., Draper, P. N., De Braekeleer, M. High-resolution chromosomal localization of the beta-gene of the human beta-globin gene complex by in situ hybridization. Cytogenet. Cell Genet. 39: 269-274, 1985. [PubMed: 4053691, related citations] [Full Text]

  667. Lin, L.-I., Lin, K.-S., Lin, K.-H., Cheng, T.-Y. A novel -32 (C-A) mutant identified in amplified genomic DNA of a Chinese beta-thalassemic patient. (Letter) Am. J. Hum. Genet. 50: 237-238, 1992. [PubMed: 1729892, related citations]

  668. Little, P. F. R., Whitelaw, E., Annison, G., Williamson, R., Kooter, J. M., Flavell, R. A., Goossens, M., Sergeant, G. R., Montgomery, D. The detection and use of hemoglobin mutants in the direct analysis of human globin genes. Blood 55: 1060-1062, 1980. [PubMed: 6246994, related citations]

  669. Liu, J.-S., Molchanova, T. P., Gu, L.-H., Wilson, J. B., Hopmeier, P., Schnedl, W., Balaun, E., Krejs, G. J., Huisman, T. H. J. Hb Graz or beta-2 (NA2) his-to-leu: a new beta chain variant observed in four families from southern Austria. Hemoglobin 16: 493-501, 1992. [PubMed: 1487420, related citations] [Full Text]

  670. Lo, Y. M. D., Hjelm, N. M., Fidler, C., Sargent, I. L., Murphy, M. F., Chamberlain, P. F., Poon, P. M. K., Redman, C. W. G., Wainscoat, J. S. Prenatal diagnosis of fetal RhD status by molecular analysis of maternal plasma. New Eng. J. Med. 339: 1734-1738, 1998. [PubMed: 9845707, related citations] [Full Text]

  671. Lokich, J. J., Moloney, W. C., Bunn, H. F., Bruckheimer, S. M., Ranney, H. M. Hemoglobin Brigham (beta 100 pro-to-leu). Hemoglobin variant associated with familial erythrocytosis. J. Clin. Invest. 52: 2060-2067, 1973. [PubMed: 4719677, related citations] [Full Text]

  672. Lorkin, P. A., Lehmann, H. Two new pathological haemoglobins: Olmsted beta 141 (H19) leu leads to arg and Malmo beta 97 (FG4) his leads to gln. Biochem. J. 119: 38P, 1970.

  673. Lorkin, P. A., Pietschmann, H., Braunsteiner, H., Lehmann, H. Structure of haemoglobin Wien beta-130 (H8) tyrosine-aspartic acid; an unstable haemoglobin variant. Acta Haemat. 51: 351-361, 1974. [PubMed: 4212355, related citations] [Full Text]

  674. Lorkin, P. A., Stephens, A. D., Beard, M. E. J., Wrigley, D. F. M., Adams, L., Lehmann, H. Haemoglobin Rahere (beta 82 lys-to-thr): a new high affinity haemoglobin associated with decreased 2,3-diphosphoglycerate binding and relative polycythaemia. Brit. Med. J. 4: 200-202, 1975. [PubMed: 124, related citations] [Full Text]

  675. Losekoot, M., Fodde, R., Harteveld, C. L., van Heeren, H., Giordano, P. C., Went, L. N., Bernini, L. F. Homozygous beta(+) thalassaemia owing to a mutation in the cleavage-polyadenylation sequence of the human beta globin gene. J. Med. Genet. 28: 252-255, 1991. [PubMed: 1856830, related citations] [Full Text]

  676. Losekoot, M., Fodde, R., van Heeren, H., Harteveld, C. L., Giordano, P. C., Bernini, L. F. A novel frameshift mutation [FSC 47 (+A)] causing beta-thalassemia in a Surinam patient. Hemoglobin 14: 467-470, 1990. [PubMed: 2283303, related citations] [Full Text]

  677. Losekoot, M., van Heeren, H., Schipper, J. J., Giordano, P. C., Bernini, L. F., Fodde, R. Rapid detection of the highly polymorphic beta globin framework by denaturing gradient gel electrophoresis. J. Med. Genet. 29: 574-577, 1992. [PubMed: 1355561, related citations] [Full Text]

  678. Lu, Y.-Q., Fan, J.-L., Liu, J.-F., Hu, H.-L., Peng, X.-H., Huang, C.-H., Huang, P.-Y., Chen, S.-S., Jia, P.-C., Yang, K.-G., Liang, C.-C., Ren, X.-D., Zuo, C.-R. Hemoglobin Jianghua (beta120(GH3) lys-to-ile): a new fast-moving variant found in China. Hemoglobin 7: 321-326, 1983. [PubMed: 6618888, related citations]

  679. Lutcher, C. L., Wilson, J. B., Gravely, M. E., Stevens, P. D., Chen, C. J., Lindeman, J. G., Wong, S. C., Miller, A., Gottleib, M., Huisman, T. H. J. Hb Leslie, an unstable hemoglobin due to deletion of glutamine residue beta 131 (H9) occurring in association with beta-thalassemia, HbC, and HbS. Blood 47: 99-112, 1976. [PubMed: 1244915, related citations]

  680. Maekawa, M., Maekawa, T., Fujiwara, N., Tabara, K., Matsuda, G. Hemoglobin Nagasaki (beta 17 glu): a new abnormal human hemoglobin found in one family in Nagasaki. Int. J. Protein Res. 2: 147-156, 1970. [PubMed: 4950989, related citations]

  681. Magenis, R. E., Donlon, T. A., Tomar, D. R. Localization of the beta-globin gene to 11p15 by in situ hybridization: utilization of chromosome 11 rearrangements. Hum. Genet. 69: 300-303, 1985. [PubMed: 3988280, related citations] [Full Text]

  682. Makhoul, N. J., Wells, R. S., Kaspar, H., Shbaklo, H., Taher, A., Chakar, N., Zalloua, P. A. Genetic heterogeneity of beta thalassemia in Lebanon reflects historic and recent population migration. Ann. Hum. Genet. 69: 55-66, 2005. [PubMed: 15638828, related citations] [Full Text]

  683. Malcorra-Azpiazu, J. J., Balda-Aguirre, M. I., Diaz-Chico, J. C., Hu, H., Wilson, J. B., Webber, B. B., Kutlar, F., Kutlar, A., Huisman, T. H. J. Hb Las Palmas or beta49 (CD8) ser-to-phe, a mildly unstable hemoglobin variant. Hemoglobin 12: 163-170, 1988. [PubMed: 3384708, related citations] [Full Text]

  684. Malone, J. I., Shah, S. C., Barness, L. A. Hemoglobin South Florida: a genetic variant with laboratory recognition of only 20% of its product. Am. J. Med. Genet. Suppl. 3: 227-231, 1987.

  685. Manca, L., Cocco, E., Cossu, G., Masala, B. Identification of Hb Hamilton or beta-11(A8)val-to-ile gene by the polymerase chain reaction amplification technique. Biochim. Biophys. Acta 1139: 17-19, 1992. [PubMed: 1610915, related citations] [Full Text]

  686. Manca, L., Formato, M., Masala, B., Gallisai, D., Orzalesi, M. Hemoglobin Hamilton (beta11 (A8) val-to-ile) in Sardinia. Hemoglobin 11: 161-167, 1987. [PubMed: 3623977, related citations] [Full Text]

  687. Maniatis, A., Bousios, T., Nagel, R. L., Balazs, T., Ueda, Y., Bookchin, R. M., Maniatis, G. M. Hemoglobin Crete (beta 129 ala-to-pro): a new high-affinity variant interacting with beta-zero and delta-beta-zero-thalassemia. Blood 54: 54-62, 1979. [PubMed: 36184, related citations]

  688. Maniatis, T., Fritsch, E. F., Lauer, J., Lawn, R. M. The molecular genetics of human hemoglobins. Annu. Rev. Genet. 14: 145-178, 1980. [PubMed: 6452087, related citations] [Full Text]

  689. Mant, M. J., Salkie, M. L., Cope, N., Appling, F., Bolch, K., Jayal-Akshmi, M., Gravely, M., Wilson, J. B., Huisman, T. H. J. Hb Alberta or beta 101 (G3) glu-to-gly, a new high-oxygen-affinity hemoglobin variant causing erythrocytosis. Hemoglobin 1: 183-194, 1977. [PubMed: 1052180, related citations] [Full Text]

  690. Maquat, L. E., Kinniburgh, A. J., Beach, L. R., Honig, G. R., Lazerson, J., Ershler, W. B., Ross, J. Processing of human beta-globin mRNA precursor to mRNA is defective in three patients with B+-thalassemia. Proc. Nat. Acad. Sci. 77: 4287-4291, 1980. [PubMed: 6933479, related citations] [Full Text]

  691. Maragoudaki, E., Kanavakis, E., Traeger-Synodinos, J., Vrettou, C., Tzetis, M., Metaxotou-Mavrommati, A., Kattamis, C. Molecular, haematological and clinical studies of the -101 C-to-T substitution of the beta-globin gene promoter in 25 beta-thalassaemia intermedia patients and 45 heterozygotes. Brit. J. Haemat. 107: 699-706, 1999. [PubMed: 10606872, related citations] [Full Text]

  692. Marengo-Rowe, A. J., Lorkin, P. A., Gallo, E., Lehmann, H. Haemoglobin Dhofar--a new variant from southern Arabia. Biochim. Biophys. Acta 168: 58-63, 1968. [PubMed: 5684629, related citations] [Full Text]

  693. Marinucci, M., Boissel, J. P., Massa, A., Wajcman, H., Tentori, L., Labie, D. Hemoglobin Maputo: a new beta-chain variant (beta 47 (CD6) asp-to-tyr) in combination with hemoglobin S, identified by high performance liquid chromatography (HPLC). Hemoglobin 7: 423-433, 1983. [PubMed: 6629824, related citations] [Full Text]

  694. Marinucci, M., Giuliani, A., Maffi, D., Massa, A., Giampaolo, A., Mavilio, F., Zannotti, M., Tentori, L. Hemoglobin Bologna (beta61 (E5) lys-to-met) an abnormal human hemoglobin with low oxygen affinity. Biochim. Biophys. Acta 668: 209-215, 1981. [PubMed: 7225407, related citations] [Full Text]

  695. Marinucci, M., Mavilio, F., Fontanarosa, P. P., Tentori, L., Brancati, C. Studies on a family with Hb J (Calabria) (beta 64 (E8) gly-to-asp). Hemoglobin 3: 327-340, 1979. [PubMed: 500375, related citations] [Full Text]

  696. Marinucci, M., Mavilio, F., Tentori, L., Alberti, R. Hemoglobin Gavello (beta 47(CD6) asp-to-gly): a new hemoglobin variant from Polesine (Italy). Hemoglobin 1: 771-779, 1977. [PubMed: 604315, related citations] [Full Text]

  697. Marti, H. R., Winterhalter, K. H., di Iorio, E. E., Lorkin, P. A., Lehmann, H. Hb Altdorf (beta 135 (H13) ala-to-pro): a new electrophoretically silent unstable haemoglobin variant from Switzerland. FEBS Lett. 63: 193-196, 1976. [PubMed: 1261680, related citations] [Full Text]

  698. Martin, H., Heupke, G., Pfleiderer, G., Woerner, W. Haemoglobin D in a Frankfurt family. Folia Haemat. 4: 233-241, 1960. [PubMed: 14421678, related citations]

  699. Martinez, G., Canizares, M. E. A second family with hemoglobin Willamette. Hemoglobin 8: 193-195, 1984. [PubMed: 6590550, related citations] [Full Text]

  700. Martinez, G., Colombo, B. Interaction between Hb S and Hb Hope in a Cuban family. Hemoglobin 8: 519-522, 1984. [PubMed: 6500990, related citations] [Full Text]

  701. Martinez, G., Lima, F., Colombo, B. Haemoglobin J Guantanamo (beta 128 (H6) ala replaced by asp): a new fast unstable haemoglobin found in a Cuban family. Biochim. Biophys. Acta 491: 1-6, 1977. [PubMed: 849451, related citations] [Full Text]

  702. Martino, T., Kaplan, F., Diamond, S., Oppenheim, A., Scriver, C. R. Probable identity by descent and discovery of familial relationships by means of a rare beta-thalassemia haplotype. Hum. Mutat. 9: 86-87, 1997. [PubMed: 8990020, related citations] [Full Text]

  703. Matsuno, Y., Yamashiro, Y., Yamamoto, K., Hattori, Y., Yamamoto, K., Ohba, Y., Miyaji, T. A possible example of gene conversion with a common beta-thalassemia mutation and chi sequence present in the beta-globin gene. Hum. Genet. 88: 357-358, 1992. [PubMed: 1733840, related citations] [Full Text]

  704. McCurdy, P. R., Fox, J., Moo-Penn, W. Apparent duplication of the beta-chain gene in man. (Abstract) Am. J. Hum. Genet. 27: 62A, 1975.

  705. McKusick, V. A. Human Genetics. Englewood Cliffs, N. J.: Prentice-Hall (pub.) 1969.

  706. Mears, J. G., Lachman, H. M., Cabannes, R., Amegnizin, K. P. E., Labie, D., Nagel, R. L. Sickle gene: its origin and diffusion from West Africa. J. Clin. Invest. 68: 606-610, 1981. [PubMed: 6268660, related citations] [Full Text]

  707. Merault, G., Keclard, L., Garin, J., Poyart, C., Blouquit, Y., Arous, N., Galacteros, F., Feingold, J., Rosa, J. Hemoglobin La Desirade, beta129 (H7) ala-to-val: a new unstable hemoglobin. Hemoglobin 10: 593-605, 1986. [PubMed: 3557994, related citations] [Full Text]

  708. Merault, G., Keclard, L., Saint-Martin, C., Jasmin, K., Campier, A., Delanoe-Garin, J., Arous, N., Fortune, R., Theodore, M., Seytor, S., Rosa, J., Blouquit, Y., Galacteros, F. Hemoglobin Roseau-Pointe a Pitre, beta90 (F6) glu-to-gly: a new variant with slight instability and low oxygen affinity. FEBS Lett. 184: 10-13, 1985. [PubMed: 3838727, related citations] [Full Text]

  709. Merghoub, T., Sanchez-Mazas, A., Tamouza, R., Lu, C. Y., Bouzid, K., Ardjoun, F. Z., Labie, D., Lapoumeroulie, C., Elion, J. Haemoglobin D-Ouled Rabah among the Mozabites: a relevant variant to trace the origin of Berber-speaking populations. Europ. J. Hum. Genet. 5: 390-396, 1997. [PubMed: 9450184, related citations]

  710. Metherall, J. E., Collins, F. S., Pan, J., Weissman, S. M., Forget, B. G. Beta-0-thalassemia caused by a base substitution that creates an alternative splice acceptor site in an intron. EMBO J. 5: 2551-2557, 1986. [PubMed: 3780671, related citations] [Full Text]

  711. Millar, C. M., Phelan, L., Bain, B. J. Diabetes mellitus diagnosed following request for haemoglobin electrophoresis. Brit. J. Haemat. 117: 778 only, 2002. [PubMed: 12060111, related citations] [Full Text]

  712. Miller, D. R., Smetanina, N. S., Gu, L.-H., Leonova, J. Y., Huisman, T. H. J. Hb Sogn or alpha-2-beta-2-14(All)leu-to-arg in combination with an alpha-thalassemia heterozygosity. Hemoglobin 20: 131-134, 1996. [PubMed: 8811316, related citations] [Full Text]

  713. Miller, D. R., Weed, R. I., Stamatoyannopoulos, G., Yoshida, A. Hemoglobin Koln disease occurring as a fresh mutation: erythrocyte metabolism and survival. Blood 38: 715-729, 1971. [PubMed: 4942314, related citations]

  714. Miller, D. R., Wilson, J. B., Kutlar, A., Huisman, T. H. J. Hb Bicetre or beta63(E7)his-to-pro in a white male: clinical observations over a period of 25 years. Am. J. Hemat. 21: 209-214, 1986. [PubMed: 3753631, related citations] [Full Text]

  715. Miller, H. I., Konkel, D. A., Leder, P. An intervening sequence of the mouse beta-globin major gene shares extensive homology only with beta-globin genes. Nature 275: 772-776, 1978. [PubMed: 568218, related citations] [Full Text]

  716. Milner, P. F., Corley, C. C., Pomeroy, W. L., Wilson, J. B., Gravely, M., Huisman, T. H. J. Thalassemia intermedia caused by heterozygosity for both beta-thalassemia and hemoglobin Saki (beta 14(A11) leu-to-pro). Am. J. Hemat. 1: 283-292, 1976. [PubMed: 998617, related citations] [Full Text]

  717. Milner, P. F., Miller, C., Grey, R., Seakins, M., De Jong, W. W., Went, L. N. Hemoglobin O Arab: interaction with hemoglobin S and hemoglobin C. New Eng. J. Med. 283: 1417-1424, 1970. [PubMed: 5481775, related citations] [Full Text]

  718. Milner, P. F. High incidence of hemoglobin G (Accra) in a rural district in Jamaica. J. Med. Genet. 4: 88-90, 1967. [PubMed: 5619995, related citations] [Full Text]

  719. Minnich, V., Hill, R. J., Khuri, P. D., Anderson, M. E. Hemoglobin Hope: a beta chain variant. Blood 25: 830-838, 1965. [PubMed: 14282052, related citations]

  720. Miranda, S. R. P., Kimura, E. M., Saad, S. T. O., Costa, F. F. Identification of Hb Zurich (beta-63 (E7) his-to-arg) by DNA analysis in a Brazilian family. Hemoglobin 18: 337-341, 1994. [PubMed: 7852089, related citations] [Full Text]

  721. Miranda, S. R. P., Kimura, E. M., Teixeira, R. C., Bertuzzo, C. S., Ramalho, A. S., Saad, S. T. O., Costa, F. F. Hb Camperdown [alpha-2-beta-2-104(G6)arg-to-ser] identified by DNA analysis in a Brazilian family. Hemoglobin 20: 147-153, 1996. [PubMed: 8811319, related citations] [Full Text]

  722. Miyaji, T., Ohba, Y., Matsuoka, M., Kudoh, H., Asano, M., Yamamoto, K., Satoh, T. Hemoglobin Karatsu: beta-120 (GH3) lysine-to-asparagine: an example of Hb Riyadh in Japan. Hemoglobin 1: 461-466, 1977. [PubMed: 893141, related citations] [Full Text]

  723. Miyaji, T., Ohba, Y., Yamamoto, K., Shibata, S., Iuchi, I., Hamilton, H. B. Hemoglobin Hijiyama: a new fast-moving hemoglobin in a Japanese family. Science 159: 204-206, 1968. [PubMed: 5634912, related citations] [Full Text]

  724. Miyaji, T., Ohba, Y., Yamamoto, K., Shibata, S., Iuchi, I., Takenaka, M. Japanese haemoglobin variant. Nature 217: 89-90, 1968. [PubMed: 5635645, related citations] [Full Text]

  725. Miyaji, T., Suzuki, H., Ohba, Y., Shibata, S. Hemoglobin Agenogi (alpha-2 beta-2 90 lys), a slow-moving hemoglobin of a Japanese family resembling hemoglobin E. Clin. Chim. Acta 14: 624-629, 1966. [PubMed: 5972415, related citations] [Full Text]

  726. Miyazaki, A., Nakanishi, T., Kishikawa, M., Nakagawa, T., Shimizu, A., Mawjood, A. H. M., Imai, K., Aoki, Y., Kikuchi, M. Compound heterozygosity for beta(+)-thalassemia (-31(A-to-G)) and a new variant with low oxygen affinity, Hb Sagami (beta-139(H17)asn-to-thr). Hemoglobin 23: 267-271, 1999. [PubMed: 10490140, related citations] [Full Text]

  727. Miyazaki, A., Nakanishi, T., Shimizu, A., Mizobuchi, M., Yamada, Y., Imai, K. Hb Kochi (beta-141(H19)leu-to-val (g.1404C-G); 144-146(HC1-3)lys-tyr-his-0 (g.1413A-T)): a new variant with increased oxygen affinity. Hemoglobin 29: 1-10, 2005. [PubMed: 15768550, related citations]

  728. Miyazaki, A., Nakanishi, T., Shimizu, A., Ninomiya, K., Nishimura, S., Imai, K. Hb Buzen [beta-138(H16)ala-to-thr (g.1395G-A)]: a new beta chain variant. Hemoglobin 27: 243-247, 2003. [PubMed: 14649315, related citations] [Full Text]

  729. Modell, B., Darlison, M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull. World Health Organ. 86: 480-487, 2008. [PubMed: 18568278, related citations] [Full Text]

  730. Modiano, D., Bancone, G., Ciminelli, B. M., Pompei, F., Blot, I., Simpore, J., Modiano, G. Haemoglobin S and haemoglobin C: 'quick but costly' versus 'slow but gratis' genetic adaptations to Plasmodium falciparum malaria. Hum. Molec. Genet. 17: 789-799, 2008. Note: Erratum: Hum. Molec. Genet. 17: 2070 only, 2008. [PubMed: 18048408, related citations] [Full Text]

  731. Modiano, D., Luoni, G., Sirima, B. S., Simpore, J., Verra, F., Konate, A., Rastrelli, E., Olivieri, A., Calissano, C., Paganotti, G. M., D'Urbano, L., Sanou, I., Sawadogo, A., Modiano, G., Coluzzi, M. Haemoglobin C protects against clinical Plasmodium falciparum malaria. Nature 414: 305-308, 2001. [PubMed: 11713529, related citations] [Full Text]

  732. Moghimi, B., Yavarian, M., Oberkanins, C., Amini, S. S. H., Khatami, S., Rouhi, S., Kahrizi, K., Najmabadi, H. Hb Dhonburi (Neapolis) (beta-126(H4)val-to-gly) identified in a family from northern Iran. Hemoglobin 28: 353-356, 2004. [PubMed: 15658193, related citations] [Full Text]

  733. Moi, P., Faa, V., Marini, M. G., Asunis, I., Ibba, G., Cao, A., Rosatelli, M. C. A novel silent beta-thalassemia mutation in the distal CACCC box affects the binding and responsiveness to EKLF. Brit. J. Haemat. 126: 881-884, 2004. [PubMed: 15352994, related citations] [Full Text]

  734. Mojzikova, R., Dolezel, P., Pavlicek, J., Mlejnek, P., Pospisilova, D., Divoky, V. Partial glutathione reductase deficiency as a cause of diverse clinical manifestations in a family with unstable hemoglobin (hemoglobin Hana, beta-63(E7) his-asn). Blood Cells Mol. Dis. 45: 219-222, 2010. [PubMed: 20692194, related citations] [Full Text]

  735. Molchanova, T. P., Postnikov, Y. V., Gu, L.-H., Huisman, T. H. J. The beta-thalassemia allele in the noble Russian family Lermontov is identified as the ATG-to-ACG change in the initiation codon. Hemoglobin 22: 283-286, 1998. [PubMed: 9629504, related citations] [Full Text]

  736. Molchanova, T. P., Postnikov, Y. V., Gu, L.-H., Prior, J. F., Raven, J. L., Bennett, J. A., Huisman, T. H. J. Hb Tigraye or beta79 (EF3) asp-to-his (GAC-to-CAC): a hemoglobin variant with increased oxygen affinity observed in an Ethiopian male. Hemoglobin 17: 247-250, 1993. [PubMed: 8330977, related citations] [Full Text]

  737. Molchanova, T. P., Postnikov, Y. V., Pobedimskaya, D. D., Smetanina, N. S., Moschan, A. A., Kazanetz, E. G., Tokarev, Y. N., Huisman, T. H. J. Hb Alesha or beta67 (E11) val-to-met: a new unstable hemoglobin variant identified through sequencing of amplified DNA. Hemoglobin 17: 217-225, 1993. [PubMed: 8330974, related citations] [Full Text]

  738. Molchanova, T. P., Wilson, J. B., Gu, L.-H., Guemira, F., Fattoum, S., Huisman, T. H. J. Hb Bab-Saadoun or beta48 (CD7) leu-to-pro, a mildly unstable variant found in an Arabian boy from Tunisia. Hemoglobin 16: 267-273, 1992. [PubMed: 1517103, related citations] [Full Text]

  739. Monn, E., Gaffney, P. J., Lehmann, H. Haemoglobin Sogn (beta 14 arginine)--a new hemoglobin variant. Scand. J. Haemat. 5: 353-360, 1968. [PubMed: 5710451, related citations]

  740. Monplaisir, N., Merault, G., Poyart, C., Rhoda, M.-D., Craescu, C., Vidaud, M., Galacteros, F., Blouquit, Y., Rosa, J. Hemoglobin S Antilles: a variant with lower solubility than hemoglobin S and producing sickle cell disease in heterozygotes. Proc. Nat. Acad. Sci. 83: 9363-9367, 1986. [PubMed: 3467311, related citations] [Full Text]

  741. Moo-Penn, W. F., Bechtel, K. C., Johnson, M. H., Jue, D. L., Therrell, B. L., Jr., Morrison, B. Y., Schmidt, R. M. Hemoglobin Fannin-Lubbock (beta 119 (GH2) gly-to-asp): a new hemoglobin variant at the alpha-1-beta-1-contact. Biochim. Biophys. Acta 453: 472-477, 1976. [PubMed: 11828, related citations] [Full Text]

  742. Moo-Penn, W. F., Bechtel, K. C., Schmidt, R. M., Johnson, M. H., Jue, D. L., Schmidt, D. E., Jr., Dunlap, W. M., Opella, S. J., Bonaventura, J., Bonaventura, C. Hemoglobin Raleigh (beta 1 valine-to-acetylalanine): structural and functional characterization. Biochemistry 16: 4872-4879, 1977. [PubMed: 20942, related citations] [Full Text]

  743. Moo-Penn, W. F., Hine, T. K., Johnson, M. H., Jue, D. L., Holland, S., George, S., Pierce, A. M., Michalski, L. A., McDonald, M. J. Hb Rancho Mirage [beta143(H21)his-to-asp]; a variant in the 2,3-DPG binding site showing normal oxygen affinity at physiological pH. Hemoglobin 16: 35-44, 1992. [PubMed: 1634360, related citations] [Full Text]

  744. Moo-Penn, W. F., Johnson, M. H., Bechtel, K. C., Jue, D. L., Therrell, B. L., Jr., Schmidt, R. M. Hemoglobins Austin and Waco: two hemoglobins with substitutions in the alpha-1-beta-2 contact region. Arch. Biochem. Biophys. 179: 86-94, 1977. [PubMed: 14597, related citations] [Full Text]

  745. Moo-Penn, W. F., Johnson, M. H., Jue, D. L., Lonser, R. Hb Hinsdale (beta139(H17)asn-to-lys): a variant in the central cavity showing reduced affinity for oxygen and 2,3-diphosphoglycerate. Hemoglobin 13: 455-464, 1989. [PubMed: 2513289, related citations] [Full Text]

  746. Moo-Penn, W. F., Johnson, M. H., McGuffey, J. E., Jue, D. L., Therrell, B. L., Jr. Hemoglobin Rio Grande (beta8 (A5) lys-to-thr): a new variant found in a Mexican-American family. Hemoglobin 7: 91-95, 1983. [PubMed: 6857757, related citations] [Full Text]

  747. Moo-Penn, W. F., Johnson, M. H., McGuffey, J. E., Jue, D. L. Hemoglobin Shelby [beta131 (H9) gln-to-lys]: a correction to the structure of hemoglobin Deaconess and hemoglobin Leslie. Hemoglobin 8: 583-593, 1984. [PubMed: 6526653, related citations] [Full Text]

  748. Moo-Penn, W. F., Jue, D. L., Bechtel, K. C., Johnson, M. H., Bemis, E., Brosious, E., Schmidt, R. M. Hemoglobin Deaconess, a new deletion mutant: beta131 (H9) glutamine deleted. Biochem. Biophys. Res. Commun. 65: 8-15, 1975. [PubMed: 1148000, related citations] [Full Text]

  749. Moo-Penn, W. F., Jue, D. L., Bechtel, K. C., Johnson, M. H., Schmidt, R. M. Hemoglobin Providence: a human hemoglobin variant occurring in two forms in vivo. J. Biol. Chem. 251: 7557-7562, 1976. [PubMed: 1002699, related citations]

  750. Moo-Penn, W. F., Jue, D. L., Johnson, M. H., Bechtel, K. C., Patchen, L. C. Hemoglobin variants and methods used for their characterization during 7 years of screening at the Center for Disease Control. Hemoglobin 4: 347-361, 1980. [PubMed: 6252122, related citations] [Full Text]

  751. Moo-Penn, W. F., Jue, D. L., Johnson, M. H., Olsen, K. W., Shih, D., Jones, R. T., Lux, S. E., Rodgers, P., Arnone, A. Hemoglobin Brockton (beta138 (H16) ala-to-pro): an unstable variant near the C-terminus of the beta-subunits with normal oxygen-binding properties. Biochemistry 27: 7614-7619, 1988. [PubMed: 3207692, related citations] [Full Text]

  752. Moo-Penn, W. F., McGuffey, J. E., Jue, D. L., Johnson, M. H., Schum, T. Hemoglobin New Mexico: beta100 (G2) pro-to-arg: a variant hemoglobin associated with erythrocytosis (BBA 32356). Biochim. Biophys. Acta 832: 192-196, 1985. [PubMed: 3840697, related citations] [Full Text]

  753. Moo-Penn, W. F., Schmidt, R. M., Jue, D. L., Bechtel, K. C., Wright, J. M., Horne, M. K., III, Haycraft, G. L., Roth, E. F., Nagel, R. L. Hemoglobin S Travis: a sickling hemoglobin with two amino acid substitutions (beta6 glutamic acid to valine and beta142 alanine to valine). Europ. J. Biochem. 77: 561-566, 1977. [PubMed: 19257, related citations] [Full Text]

  754. Moo-Penn, W. F., Schneider, R. G., Andrian, S., Das, D. K. Hemoglobin Detroit: beta 95 (FG2) lysine-to-asparagine. Biochim. Biophys. Acta 536: 283-288, 1978. [PubMed: 708768, related citations] [Full Text]

  755. Moo-Penn, W. F., Schneider, R. G., Shih, T., Jones, R. T., Govindarajan, S., Govindarajan, P. G., Patchen, L. C. Hemoglobin Ohio (beta 142 ala-to-asp): a new abnormal hemoglobin with high oxygen affinity and erythrocytosis. Blood 56: 246-250, 1980. [PubMed: 7397380, related citations]

  756. Moo-Penn, W. F., Wolff, J. A., Simon, G., Vacek, M., Jue, D. L., Johnson, M. H. Hemoglobin Presbyterian: beta 108(G10) asn-to-lys. A haemoglobin variant with low oxygen affinity. FEBS Lett. 92: 53-56, 1978. [PubMed: 668922, related citations] [Full Text]

  757. Moo-Penn, W. F. Personal Communication. Atlanta, Ga. 1981.

  758. Moon, A. M., Ley, T. J. Conservation of the primary structure, organization, and function of the human and mouse beta-globin locus-activating regions. Proc. Nat. Acad. Sci. 87: 7693-7697, 1990. [PubMed: 2217202, related citations] [Full Text]

  759. Morton, C. C., Kirsch, I. R., Taub, R., Orkin, S. H., Brown, J. A. Localization of the beta-globin gene by chromosomal in situ hybridization. Am. J. Hum. Genet. 36: 576-585, 1984. [PubMed: 6587773, related citations]

  760. Mrad, A., Blouquit, Y., Lacombe, C., Blibech, R., Arous, N., Bardakdjian, J., Kastally, R., Rosa, J., Galacteros, F. Hb Tunis: (beta124 (H2) pro-to-ser), a new beta-chain variant identified by HPLC. Hemoglobin 12: 23-30, 1988. [PubMed: 3384695, related citations] [Full Text]

  761. Muller, C. J., Kingma, S. Haemoglobin Zurich beta 63 arg. Biochim. Biophys. Acta 50: 595, 1961. [PubMed: 13726693, related citations] [Full Text]

  762. Murawski, K., Carta, S., Sorcini, M., Tentori, L., Vivaldi, G., Antonini, E., Brunori, M., Wyman, J., Bucci, E., Rossi-Fanelli, A. Observations on the structure and behavior of hemoglobin M (Radom). Arch. Biochem. 111: 197-201, 1965. [PubMed: 5851873, related citations] [Full Text]

  763. Murru, S., Loudianos, G., Deiana, M., Camaschella, C., Sciarratta, G. V., Agosti, S., Parodi, M. I., Cerruti, P., Cao, A., Pirastu, M. Molecular characterization of beta-thalassemia intermedia in patients of Italian descent and identification of three novel beta-thalassemia mutations. Blood 77: 1342-1347, 1991. [PubMed: 2001456, related citations]

  764. Murru, S., Pischedda, M. C., Cao, A., Rosatelli, M. C., Pirastu, M., Sciarratta, G. V. A promoter mutation of the beta-globin gene (-101 C-to-T) has an age-related expression pattern. (Letter) Blood 81: 2818-2819, 1993. [PubMed: 7683931, related citations]

  765. Murru, S., Poddie, D., Sciarratta, G. V., Agosti, S., Baffico, M., Melevendi, C., Pirastu, M., Cao, A. A novel beta-globin structural mutant, Hb Brescia (beta114 leu-to-pro), causing a severe beta-thalassemia intermedia phenotype. Hum. Mutat. 1: 124-128, 1992. [PubMed: 1301199, related citations] [Full Text]

  766. Musumeci, S., Schiliro, G., Fisher, A., Musco, A., Marinucci, M., Mavilio, F., Fontanarosa, P. P., Tentori, L. Hb J Baltimore (beta 16 (A13) gly-to-asp) in association with beta-thalassemia in a Sicilian family. Hemoglobin 3: 459-464, 1979. [PubMed: 511585, related citations] [Full Text]

  767. Nagel, R. L., Daar, S., Romero, J. R., Suzuka, S. M., Gravell, D., Bouhassira, E., Schwartz, R. S., Fabry, M. E., Krishnamoorthy, R. Hb S-Oman heterozygote: a new dominant sickle syndrome. Blood 92: 4375-4382, 1998. [PubMed: 9834244, related citations]

  768. Nagel, R. L., Fabry, M. E., Pagnier, J., Zohoun, I., Wajcman, H., Baudin, V., Labie, D. Hematologically and genetically distinct forms of sickle cell anemia in Africa: the Senegal type and the Benin type. New Eng. J. Med. 312: 880-884, 1985. [PubMed: 2579336, related citations] [Full Text]

  769. Nagel, R. L., Lin, M. J., Witkowska, H. E., Fabry, M. E., Bestak, M., Hirsch, R. E. Compound heterozygosity for hemoglobin C and Korle-Bu: moderate microcytic hemolytic anemia and acceleration of crystal formation. Blood 82: 1907-1912, 1993. Note: Erratum: Blood 83: 3105 only, 1994. [PubMed: 7691242, related citations]

  770. Nagel, R. L., Lynfield, J., Johnson, J., Landau, L., Bookchin, R. M., Harris, M. B. Hemoglobin Beth Israel: a mutant causing clinically apparent cyanosis. New Eng. J. Med. 295: 125-130, 1976. [PubMed: 1272328, related citations] [Full Text]

  771. Nakamura, T., Araki, M., Kuzuo, Y., Harano, T., Harano, K., Ohba, Y. Hb Nagasaki [beta-17(A14)lys-to-glu]: a second case found in a Japanese family. Hemoglobin 21: 187-188, 1997. [PubMed: 9101287, related citations] [Full Text]

  772. Nakanishi, T., Miyazaki, A., Kishikawa, M., Shimizu, A., Aoki, Y., Kikuchi, M. Hb Peterborough [beta-111(G13)val-to-phe] in Japan: rapid identification by ESI/MS using proteolytic digests of oxidized globin. Hemoglobin 22: 23-35, 1998. [PubMed: 9494045, related citations] [Full Text]

  773. Nakanishi, T., Miyazaki, A., Kishikawa, M., Shimizu, A., Kishida, O., Sumi, S., Tsubakio, T., Imai, K. A new hemoglobin variant found during Hb A(1c) measurement: Hb Hokusetsu [beta-52(D3)asp-to-gly]. Hemoglobin 22: 355-371, 1998. [PubMed: 9730366, related citations] [Full Text]

  774. Nakatsuji, T., Miwa, S., Ohba, Y., Hattori, Y., Miyaji, T., Hino, S., Matsumoto, N. A new unstable hemoglobin, Hb Yokohama (beta31 (B13) leu-to-pro), causing hemolytic anemia. Hemoglobin 5: 667-678, 1981. [PubMed: 7338469, related citations] [Full Text]

  775. Nakatsuji, T., Miwa, S., Ohba, Y., Hattori, Y., Miyaji, T., Miyata, H., Shinohara, T., Hori, T., Takayama, J. Hemoglobin Miyashiro (beta23 (B5) val-to-gly): an electrophoretically silent variant discovered by the isopropanol test. Hemoglobin 5: 653-666, 1981. [PubMed: 7338468, related citations] [Full Text]

  776. Naritomi, Y., Naito, Y., Nakashima, H., Yokota, E., Imamura, T. A substitution of cytosine for thymine in codon 110 of the human beta-globin gene is a novel cause of beta-thalassemia phenotypes. Hum. Genet. 80: 11-15, 1988. [PubMed: 3417300, related citations] [Full Text]

  777. Navas, P. A., Li, Q., Peterson, K. R., Swank, R. A., Rohde, A., Roy, J., Stamatoyannopoulos, G. Activation of the beta-like globin genes in transgenic mice is dependent on the presence of the beta-locus control region. Hum. Molec. Genet. 11: 893-903, 2002. [PubMed: 11971871, related citations] [Full Text]

  778. Navas, P. A., Swank, R. A., Yu, M., Peterson, K. R., Stamatoyannopoulos, G. Mutation of a transcriptional motif of a distant regulatory element reduces the expression of embryonic and fetal globin genes. Hum. Molec. Genet. 12: 2941-2948, 2003. [PubMed: 14506128, images, related citations] [Full Text]

  779. Necheles, T. F., Allen, D. M., Gerald, P. S. The many forms of thalassemia: definition and classification of the thalassemia syndromes. Ann. N.Y. Acad. Sci. 165: 5-12, 1969. [PubMed: 5260168, related citations] [Full Text]

  780. Neel, J. V., Kaplan, E., Zuelzer, W. W. Further studies of hemoglobin C. I. A description of three additional families segregating for hemoglobin C and sickle cell hemoglobin. Blood 8: 724-734, 1953. [PubMed: 13066514, related citations]

  781. Neel, J. V. The inheritance of sickle cell anemia. Science 110: 64-66, 1949. [PubMed: 17774955, related citations] [Full Text]

  782. Negri Arjona, S., Eloy-Garcia, J. M., Gu, L.-H., Smetanina, N. S., Huisman, T. H. J. The dominant beta-thalassaemia in a Spanish family is due to a frameshift that introduces an extra CGG codon (=arginine) at the 5-prime end of the second exon. Brit. J. Haemat. 93: 841-844, 1996. [PubMed: 8703815, related citations] [Full Text]

  783. Negri Arjona, S., Maldonado Eloy-Garcia, J., Molchanova, T. P., Wilson, J. B., Gu, L.-H., Huisman, T. H. J. Hb Brockton (beta-138 (H16) ala-to-pro) observed in a Spanish girl. Hemoglobin 16: 511-514, 1992. [PubMed: 1487422, related citations] [Full Text]

  784. Ngiwsara, L., Srisomsap, C., Winichagoon, P., Fucharoen, S., Svasti, J. Hb Kodaira II [beta-146(HC3)his-to-gln] detected in Thailand. Hemoglobin 27: 37-39, 2003. [PubMed: 12603092, related citations] [Full Text]

  785. Niazi, G. A., Zamanianpoor, M., Ala, F. Hemoglobin G Saskatoon in association with PNH in an Iranian soldier. Hemoglobin 5: 85-87, 1981. [PubMed: 7204096, related citations] [Full Text]

  786. Noguera, N. I., Cardozo, M. A., Gonzalez, F. A., Benavente, C., Milani, A. C., Villegas, A. Hb Agenogi [beta-90(F6)glu-to-lys] in an Argentinean girl. Hemoglobin 26: 201-203, 2002. [PubMed: 12144066, related citations] [Full Text]

  787. North, M. L., Duwig, I., Riou, J., Prome, D., Yapo, A. P., Kister, J., Bardakdjian-Michau, J., Cazenave, J. P., Wajcman, H. Hb Tsukumi (beta-117(G19)his-to-tyr) found in a Moroccan woman. Hemoglobin 25: 107-110, 2001. [PubMed: 11300344, related citations] [Full Text]

  788. Novy, M. J., Edwards, M. J., Metcalfe, J. Hemoglobin Yakima. II. High blood oxygen affinity associated with compensatory erythrocytosis and normal hemodynamics. J. Clin. Invest. 46: 1848-1854, 1967. [PubMed: 6061752, related citations] [Full Text]

  789. Novy, M. J., Edwards, M. J., Peterson, E. N., Metcalfe, J. Hemoglobin Yakima: oxygen hemoglobin equilibrium and cardiodynamic effects. (Abstract) Clin. Res. 15: 133, 1967.

  790. Nusapan, R., Conant, J. L. Hemoglobin Southampton (Casper) inclusions resembling intracellular parasites. Blood 141: 3126 only, 2023. [PubMed: 37347497, related citations] [Full Text]

  791. Nute, P. E., Stamatoyannopoulos, G., Hermodson, M. A., Roth, D. Hemoglobinopathic erythrocytosis due to a new electrophoretically silent variant, hemoglobin San Diego (beta 109 (G11) val-to-met). J. Clin. Invest. 53: 320-328, 1974. [PubMed: 4808644, related citations] [Full Text]

  792. O'Donnell, A., Premawardhena, A., Arambepola, M., Samaranayake, R., Allen, S. J., Peto, T. E. A., Fisher, C. A., Cook, J., Corran, P. H., Olivieri, N. F., Weatherall, D. J. Interaction of malaria with a common form of severe thalassemia in an Asian population. Proc. Nat. Acad. Sci. 106: 18716-18721, 2009. [PubMed: 19841268, images, related citations] [Full Text]

  793. O'Gorman, P., Lehmann, H., Allsopp, K. M., Sukumaran, P. K. Sickle cell haemoglobin K disease. Brit. Med. J. 2: 1381-1382, 1963. [PubMed: 14063031, related citations] [Full Text]

  794. Ockelford, P. A., Liang, A. Y., Wells, R. M., Vissers, M., Brennan, S. O., Williamson, D., Carrell, R. W. Hemoglobin Volga, beta27 (B9) ala-to-asp: functional and clinical correlations of an unstable hemoglobin. Hemoglobin 4: 295-306, 1980. [PubMed: 7419425, related citations] [Full Text]

  795. Oehme, R., Kohne, E., Kleihauer, E., Horst, J. Hb M Milwaukee: direct detection of the beta-globin gene mutation in three generations of an afflicted family. Hum. Genet. 64: 376-379, 1983. [PubMed: 6311728, related citations] [Full Text]

  796. Ogata, K., Ito, T., Okazaki, T., Dan, K., Nomura, T., Nozawa, Y., Kajita, A. Hemoglobin Sendagi (beta42 phe-to-val): a new unstable hemoglobin variant having an amino acid substitution at CD1 of the beta-chain. Hemoglobin 10: 469-481, 1986. [PubMed: 3781864, related citations] [Full Text]

  797. Ohashi, J., Naka, I., Patarapotikul, J., Hananantachai, H., Brittenham, G., Looareesuwan, S., Clark, A. G., Tokunaga, K. Extended linkage disequilibrium surrounding the hemoglobin E variant due to malarial selection. Am. J. Hum. Genet. 74: 1198-1208, 2004. [PubMed: 15114532, images, related citations] [Full Text]

  798. Ohba, Y., Ami, M., Imai, K., Komatsu, K., Amatsu, K. Hb Masuda [beta114(G16)leu-to-met, 119(GH2)gly-to-asp], a hemoglobin with two substitutions in the beta chain. Hemoglobin 13: 753-759, 1989. [PubMed: 2634673, related citations] [Full Text]

  799. Ohba, Y., Hasegawa, Y., Amino, H., Miwa, S., Nakatsuji, T., Hattori, Y., Miyaji, T. Hemoglobin Saitama or beta117 (G19) his-to-pro, a new variant causing hemolytic disease. Hemoglobin 7: 47-56, 1983. [PubMed: 6687721, related citations] [Full Text]

  800. Ohba, Y., Hattori, Y., Ami, M., Yagami, H., Miyaji, T., Tani, Y. Hb Cocody [beta21(B3)asp-to-asn] and Hb Yusa [beta21(B3)asp-to-tyr] found in Japan. Hemoglobin 14: 109-114, 1990. [PubMed: 2384310, related citations] [Full Text]

  801. Ohba, Y., Hattori, Y., Fuyuno, K., Takeda, I., Matsuoka, M., Yoshinaka, H., Satoh, T., Miyaji, T. Two further examples of Hb Hirose, beta37 (C3) trp-to-ser. Hemoglobin 7: 191-193, 1983. [PubMed: 6671905, related citations]

  802. Ohba, Y., Hattori, Y., Miyaji, T., Takasaki, M., Shirahama, M., Fujisawa, K., Nakatsuji, T., Miwa, S. Purification and properties of hemoglobin Miyashiro. Hemoglobin 8: 515-518, 1984. [PubMed: 6500989, related citations] [Full Text]

  803. Ohba, Y., Hattori, Y., Sakata, S., Yamashiro, Y., Okayama, N., Hirano, T., Nakanishi, T., Miyazaki, A., Shimizu, A. Hb Niigata [beta-1(NA1)val-to-leu]: the fifth variant with retention of the initiator methionine and partial acetylation. Hemoglobin 21: 179-186, 1997. [PubMed: 9101286, related citations] [Full Text]

  804. Ohba, Y., Imai, K., Kumada, I., Ohsawa, A., Miyaji, T. Hb Moriguchi or beta97(FG4)his-to-tyr substitution at the alpha(1)-beta(2) interface. Hemoglobin 13: 367-376, 1989. [PubMed: 2775360, related citations] [Full Text]

  805. Ohba, Y., Imanaka, M., Matsuoka, M., Hattori, Y., Miyaji, T., Funaki, C., Shibata, K., Shimokata, H., Kuzuya, F., Miwa, S. A new unstable, high oxygen affinity hemoglobin: Hb Nagoya or beta97 (FG4) his-to-pro. Hemoglobin 9: 11-24, 1985. [PubMed: 3838976, related citations] [Full Text]

  806. Ohba, Y., Matsuoka, M., Fuyuno, K., Yamamoto, K., Nishijima, S., Miyaji, T. Further studies on hemoglobin Hofu, beta 126 (H4) val-to-glu, with special reference to its stability. Hemoglobin 5: 89-95, 1981. [PubMed: 7204097, related citations] [Full Text]

  807. Ohba, Y., Matsuoka, M., Miyaji, T., Shibuya, T., Sakuragawa, M. Hemoglobin Bristol or beta 67 (E11) val-to-asp in Japan. Hemoglobin 9: 79-85, 1985. [PubMed: 3997544, related citations] [Full Text]

  808. Ohba, Y., Miyaji, T., Hirosaki, T., Matsuoka, M., Koresawa, M., Iuchi, I. Occurrence of hemoglobin G Coushatta in Japan. Hemoglobin 2: 437-441, 1978. [PubMed: 721611, related citations] [Full Text]

  809. Ohba, Y., Miyaji, T., Ihzumi, T., Shibata, A. Hb Bushwick, an unstable hemoglobin with tendency to lose heme. Hemoglobin 9: 517-523, 1985. [PubMed: 3841345, related citations] [Full Text]

  810. Ohba, Y., Miyaji, T., Matsuoka, M., Sugiyama, K., Suzuki, T., Sugiura, T. Hemoglobin Mizuho or beta 68 (E12) leucine-to-proline, a new unstable variant associated with severe hemolytic anemia. Hemoglobin 1: 467-478, 1977. [PubMed: 893142, related citations] [Full Text]

  811. Ohba, Y., Miyaji, T., Matsuoka, M., Ueda, S., Iuchi, I., Shibata, S. Hemoglobin Tokuchi: beta131 glutamine-to-glutamic acid, an example of hemoglobin Camden in Japan. Acta Haemat. Jpn. 38: 1-7, 1975. [PubMed: 1173714, related citations]

  812. Ohba, Y., Miyaji, T., Matsuoka, M., Yamaguchi, K., Yonemitsu, H., Ishii, T., Shibata, S. Hemoglobin Chiba: Hb Hammersmith in a Japanese girl. Acta Haemat. Jpn. 38: 53-58, 1975. [PubMed: 1173718, related citations]

  813. Ohba, Y., Miyaji, T., Murakami, M., Kadowaki, S., Fujita, T., Oimomi, M., Hatanaka, H., Ishikawa, K., Baba, S., Hitaka, K., Imai, K. Hb Himeji or beta140 (H18) ala-to-asp: a slightly unstable hemoglobin with increased beta-N-terminal glycation. Hemoglobin 10: 109-126, 1986. [PubMed: 3754244, related citations] [Full Text]

  814. Ohba, Y., Miyaji, T., Shibata, S. Identical substitution in Hb Ube-1 and Hb Koln. Nature N.B. 243: 205-207, 1973. [PubMed: 4514958, related citations] [Full Text]

  815. Ohba, Y., Yamada, H., Takamatsu, S., Imai, K. Hb Tsurumai [beta-82(EF6)lys-to-gln]: a new Hb variant with high oxygen affinity and erythrocytosis. Hemoglobin 20: 141-146, 1996. [PubMed: 8811318, related citations] [Full Text]

  816. Ohta, Y., Yamaoka, K., Sumida, I., Yanase, T. Haemoglobin Miyada, a beta-delta fusion peptide (anti-Lepore) type discovered in a Japanese family. Nature N.B. 234: 218-220, 1971. [PubMed: 5288810, related citations] [Full Text]

  817. Old, J. M., Ward, R. H. T., Petrou, M., Karagozlu, F., Modell, B., Weatherall, D. J. First-trimester fetal diagnosis for hemoglobinopathies: three cases. Lancet 320: 1413-1416, 1982. Note: Originally Volume II. [PubMed: 6129504, related citations] [Full Text]

  818. Opfell, R. W., Lorkin, P. A., Lehmann, H. Hereditary non-spherocytic haemolytic anaemia with post-splenectomy inclusion bodies and pigmenturia caused by an unstable haemoglobin Santa Ana--beta 88 (F4) leucine-proline. J. Med. Genet. 5: 292-297, 1968. [PubMed: 5713642, related citations] [Full Text]

  819. Oppenheim, A., Oron, V., Filon, D., Fearon, C. C., Rachmilewitz, E. A., Kazazian, H. H., Jr., Rund, D. Sporadic alleles, including a novel mutation, characterize beta-thalassemia in Ashkenazi Jews. Hum. Mutat. 2: 155-157, 1993. [PubMed: 8318995, related citations] [Full Text]

  820. Oribe, Y., Hamaguchi, K., Kusuda, Y., Harano, K., Harano, T., Iwasaki, Y., Kotegawa, K., Sakata, T. Hb Tsukumi (beta-117(G19)his-to-tyr): a new hemoglobin variant found in a Japanese male. Hemoglobin 24: 117-123, 2000. [PubMed: 10870882, related citations] [Full Text]

  821. Orkin, S. H., Alter, B. P., Altay, C., Mahoney, M. J., Lazarus, H., Hobbins, J. C., Nathan, D. G. Application of endonuclease mapping to the analysis and prenatal diagnosis of thalassemias caused by globin-gene deletion. New Eng. J. Med. 299: 166-172, 1978. [PubMed: 661890, related citations] [Full Text]

  822. Orkin, S. H., Antonarakis, S. E., Loukopoulos, D. Abnormal processing of beta(Knossos) RNA. Blood 64: 311-313, 1984. [PubMed: 6733281, related citations]

  823. Orkin, S. H., Cheng, T.-C., Antonarakis, S. E., Kazazian, H. H., Jr. Thalassemia due to a mutation in the cleavage-polyadenylation signal of the human beta-globin gene. EMBO J. 4: 453-456, 1985. [PubMed: 4018033, related citations] [Full Text]

  824. Orkin, S. H., Goff, S. C. Nonsense and frameshift mutations in beta-thalassemia detected in cloned beta-globin genes. J. Biol. Chem. 256: 9782-9784, 1981. [PubMed: 6985481, related citations]

  825. Orkin, S. H., Kazazian, H. H., Jr., Antonarakis, S. E., Goff, S. C., Boehm, C. D., Sexton, J. P., Waber, P. G., Giardina, P. J. V. Linkage of beta-thalassaemic mutations and beta-globin gene polymorphisms with DNA polymorphisms in the human beta-globin gene cluster. Nature 296: 627-631, 1982. [PubMed: 6280057, related citations] [Full Text]

  826. Orkin, S. H., Kazazian, H. H., Jr., Antonarakis, S. E., Ostrer, H., Goff, S. C., Sexton, J. P. Abnormal RNA processing due to the exon mutation of beta-E-globin gene. Nature 300: 768-769, 1982. [PubMed: 7177196, related citations] [Full Text]

  827. Orkin, S. H., Kolodner, R., Michelson, A., Husson, R. Cloning and direct examination of a structurally abnormal human beta-zero-thalassemia globin gene. Proc. Nat. Acad. Sci. 77: 3558-3562, 1980. [PubMed: 6251466, related citations] [Full Text]

  828. Orkin, S. H., Little, P. F. R., Kazazian, H. H., Jr., Boehm, C. D. Improved detection of the sickle mutation by DNA analysis: application to prenatal diagnosis. New Eng. J. Med. 307: 32-36, 1982. [PubMed: 6176867, related citations] [Full Text]

  829. Orkin, S. H., Old, J. M., Weatherall, D. J., Nathan, D. G. Partial deletion of beta-globin gene DNA in certain patients with beta-zero-thalassemia. Proc. Nat. Acad. Sci. 76: 2400-2404, 1979. [PubMed: 287080, related citations] [Full Text]

  830. Orkin, S. H., Sexton, J. P., Cheng, T.-C., Goff, S. C., Giardina, P. J. V., Lee, J. I., Kazazian, H. H., Jr. ATA box transcription mutation in beta-thalassemia. Nucleic Acids Res. 11: 4727-4734, 1983. [PubMed: 6308558, related citations] [Full Text]

  831. Orkin, S. H., Sexton, J. P., Goff, S. C., Kazazian, H. H., Jr. Inactivation of an acceptor RNA splice site by a short deletion in beta-thalassemia. J. Biol. Chem. 258: 7249-7251, 1983. [PubMed: 6190800, related citations]

  832. Oron, V., Filon, D., Oppenheim, A., Rund, D. Severe thalassaemia intermedia caused by interaction of homozygosity for alpha-globin gene triplication with heterozygosity for beta zero-thalassaemia. Brit. J. Haemat. 86: 377-379, 1994. [PubMed: 8199028, related citations] [Full Text]

  833. Orringer, E. P., Felice, A., Reese, A., Wilson, J. B., Lam, H., Gravely, M. E., Huisman, T. H. J. Hemoglobin Nottingham (beta (FG5) 98 val-to-gly) in a Caucasian male: clinical and biosynthetic studies. Hemoglobin 2: 315-332, 1978. [PubMed: 701088, related citations] [Full Text]

  834. Osgood, E. E., Jones, R. T., Brimhall, B., Koler, R. D. Hemoglobin Yakima: clinical and biochemical studies. (Abstract) Clin. Res. 15: 134, 1967.

  835. Ottolenghi, S., Comi, P., Giglioni, B., Tolstoshev, P., Lanyon, W. G., Mitchell, G. J., Williamson, R., Russo, G., Musumeci, S., Schilliro, G., Tsistrakis, G. A., Charache, S., Wood, W. G., Clegg, J. B., Weatherall, D. J. Delta-beta-thalassemia is due to a gene deletion. Cell 9: 71-80, 1976. [PubMed: 975241, related citations] [Full Text]

  836. Ottolenghi, S., Giglioni, B. The deletion in a type of delta-zero-beta-zero-thalassemia begins in an inverted AluI repeat. Nature 300: 770-771, 1982. [PubMed: 6184621, related citations] [Full Text]

  837. Ottolenghi, S., Lanyon, W. G., Paul, J., Williamson, R., Weatherall, D. J., Clegg, J. B., Pritchard, J., Pootrakul, S., Boon, W. H. Gene deletion as the cause of alpha-thalassaemia: the severe form of alpha thalassaemia is caused by haemoglobin gene deletion. Nature 251: 389-391, 1974. [PubMed: 4138824, related citations] [Full Text]

  838. Ottolenghi, S., Lanyon, W. G., Williamson, R., Weatherall, D. J., Clegg, J. B., Pitcher, C. S. Human globin gene analysis for a patient with 'beta-zero: delta-beta-zero' thalassemia. Proc. Nat. Acad. Sci. 72: 2294-2299, 1975. [PubMed: 49057, related citations] [Full Text]

  839. Outeirino, J., Casey, R., White, J. M., Lehmann, H. Haemoglobin Madrid beta 115 (G17) alanine-to-proline: an unstable variant associated with haemolytic anaemia. Acta Haemat. 52: 53-60, 1974. [PubMed: 4212046, related citations] [Full Text]

  840. Owen, M. C., Ockelford, P. A., Wells, R. M. G. HB Howick (beta37 (C3) trp-to-gly): a new high oxygen affinity variant of the alpha-1-beta-2 contact. Hemoglobin 17: 513-521, 1993. [PubMed: 8144352, related citations] [Full Text]

  841. Ozsoylu, S. Homozygous hemoglobin D Punjab. Acta Haemat. 43: 353-359, 1970. [PubMed: 4991321, related citations] [Full Text]

  842. Padanilam, B. J., Huisman, T. H. J. The beta-0-thalassemia in an American black family is due to a single nucleotide substitution in the acceptor splice junction of the second intervening sequence. Am. J. Hemat. 22: 259-263, 1986. [PubMed: 2424301, related citations] [Full Text]

  843. Pagano, L., Lacerra, G., Camardella, L., De Angioletti, M., Fioretti, G., Maglione, G., de Bonis, C., Guarino, E., Viola, A., Cutolo, R., De Rosa, L., Carestia, C. Hemoglobin Neapolis, beta-126(H4)val-to-gly: a novel beta-chain variant associated with a mild beta-thalassemia phenotype and displaying anomalous stability features. Blood 78: 3070-3075, 1991. [PubMed: 1954392, related citations]

  844. Pagano, L., Salzano, A. M., Carbone, V., Iannelli, D., Viola, A., Pollio, F., Prossomariti, L., David, O., Ricco, G., Pucci, P. Hb Cardarelli [beta-86(F2)ala-to-pro]: a new unstable and hyperaffine variant in association with beta(+)-thalassemia. Hemoglobin 28: 103-115, 2004. [PubMed: 15182052, related citations] [Full Text]

  845. Pagnier, J., Baudin-Chich, V., Lacaze, N., Bohn, B., Poyart, C. Haemoglobin beta23 val-to-ile produced in Escherichia coli facilitates Hb S polymerization. Brit. J. Haemat. 74: 531-534, 1990. [PubMed: 2189492, related citations] [Full Text]

  846. Pagnier, J., Mears, J. G., Dunda-Belkhodja, O., Schaefer-Rego, K. E., Beldjord, C., Nagel, R. L., Labie, D. Evidence for the multicentric origin of the sickle cell hemoglobin gene in Africa. Proc. Nat. Acad. Sci. 81: 1771-1773, 1984. [PubMed: 6584911, related citations] [Full Text]

  847. Paniker, N. V., Lin, K. D., Krantz, S. B., Flexner, J. M., Wasserman, B. K., Puett, D. Hemoglobin Vanderbilt (beta 89 ser-to-arg): a new hemoglobin with high oxygen affinity and compensatory erythrocytosis. Brit. J. Haemat. 39: 249-258, 1978. [PubMed: 678476, related citations] [Full Text]

  848. Papassotiriou, I., Traeger-Synodinos, J., Prome, D., Kister, J., Vrettou, C., Xaidara, A., Marden, M., Stamoulakatou, A., Wajcman, H., Kanavakis, E. Hb Sitia (beta-128(H6)ala-to-val): an unstable variant with a substitution in the alpha-1-beta-1 interface. Hemoglobin 25: 45-56, 2001. [PubMed: 11300349, related citations] [Full Text]

  849. Park, S. S., Barnetson, R., Kim, S. W., Weatherall, D. J., Thein, S. L. A spontaneous deletion of beta33/34 val in exon 2 of the beta globin gene (Hb Korea) produces the phenotype of dominant beta thalassaemia. Brit. J. Haemat. 78: 581-582, 1991. [PubMed: 1911355, related citations] [Full Text]

  850. Pasvol, G. Protective hemoglobinopathies and Plasmodium falciparum transmission. Nature Genet. 42: 284-285, 2010. [PubMed: 20348963, related citations] [Full Text]

  851. Pauling, L., Itano, H. A., Singer, S. J., Wells, I. C. Sickle cell anemia, a molecular disease. Science 110: 543-548, 1949. [PubMed: 15395398, related citations] [Full Text]

  852. Pearson, H. A., Gallagher, D., Chilcote, R., Sullivan, E., Wilimas, J., Espeland, M., Ritchey, A. K., Cooperative Study of Sickle Cell Disease. Developmental pattern of splenic dysfunction in sickle cell disorders. Pediatrics 76: 392-397, 1985. [PubMed: 2412200, related citations]

  853. Perea, F. J., Magana, M. T., Esparza, M. A., Ibarra, B. A frameshift at codons 77/78 (-C): a novel beta-thalassemia mutation. Hemoglobin 28: 261-265, 2004. [PubMed: 15481896, related citations] [Full Text]

  854. Perichon, B., Ragusa, A., Lapoumeroulie, C., Romand, A., Moi, P., Ikuta, T., Labie, D., Elion, J., Krishnamoorthy, R. Inter-ethnic polymorphism of the beta-globin gene locus control region (LCR) in sickle-cell anemia patients. Hum. Genet. 91: 464-468, 1993. [PubMed: 8314558, related citations] [Full Text]

  855. Perrault, J., Fairbanks, V. F., McCormick, D. J., Kubik, K., Madden, B. J., Holmes, M. W., Hoyer, J. D. Hemoglobin Rockford, beta68(E12)leu-to-phe: a new HB variant associated with mild anemia. (Abstract) Blood 90 (Suppl. 1): 30b, 1997.

  856. Persons, D. A., Nienhuis, A. W. Gene therapy for the hemoglobin disorders: past, present, and future. (Commentary) Proc. Nat. Acad. Sci. 97: 5022-5024, 2000. [PubMed: 10805762, related citations] [Full Text]

  857. Perutz, M. F., Fermi, G., Shih, T.-B. Structure of deoxyhemoglobin Cowtown (HC3(146)beta his-to-leu): origin of the alkaline Bohr effect and electrostatic interactions in hemoglobin. Proc. Nat. Acad. Sci. 81: 4781-4784, 1984. [PubMed: 6589624, related citations] [Full Text]

  858. Perutz, M. F., Lehmann, H. Molecular pathology of human hemoglobin. Nature 219: 902-909, 1968. [PubMed: 5691676, related citations] [Full Text]

  859. Perutz, M. F., Pulsinelli, P. D., Ranney, H. M. Structure and subunit interaction of haemoglobin M Milwaukee. Nature N.B. 237: 259-263, 1972. [PubMed: 4338724, related citations] [Full Text]

  860. Perutz, M. F., Pulsinelli, P., Eyck, L. T., Kilmartin, J. V., Shibata, S., Miyaji, Y., Iuchi, I., Hamilton, H. B. Haemoglobin Hiroshima and the mechanism of the alkaline Bohr effect. Nature N.B. 232: 147-149, 1971. [PubMed: 5285571, related citations] [Full Text]

  861. Peters, J., Andrews, S. J., Loutit, J. F., Clegg, J. B. A mouse beta-globin mutant that is an exact model of hemoglobin Rainier in man. Genetics 110: 709-721, 1985. [PubMed: 3839762, related citations] [Full Text]

  862. Peterson, K. R., Clegg, C. H., Navas, P. A., Norton, E. J., Kimbrough, T. G., Stamatoyannopoulos, G. Effect of deletion of 5-prime HS3 or 5-prime HS2 of the human beta-globin locus control region on the developmental regulation of globin gene expression in beta-globin locus yeast artificial chromosome transgenic mice. Proc. Nat. Acad. Sci. 93: 6605-6609, 1996. [PubMed: 8692864, related citations] [Full Text]

  863. Philippe, M., Larondelle, Y., Vaerman, J. L., Martiat, P., Galacteros, F., Wajcman, H., Lambert, M. Hb Tubingen [beta-106(G8) leu-to-gln] in a Belgian family. Hemoglobin 17: 373-378, 1993. [PubMed: 8226097, related citations] [Full Text]

  864. Pierce, L. E., Rath, C. E., McCoy, K. A new hemoglobin variant with sickling properties. New Eng. J. Med. 268: 862-866, 1963. [PubMed: 13943409, related citations] [Full Text]

  865. Pillers, D. M., Jones, M., Head, C., Jones, R. T. Hb Hope [beta-136(H14)gly-to-asp] and Hb E [beta-26(B8)glu-to-lys]: compound heterozygosity in a Thai Mien family. Hemoglobin 16: 81-84, 1992. [PubMed: 1634366, related citations] [Full Text]

  866. Pinkerton, P. H., Wilson, J. B., Lam, H., Williams, D., Huisman, T. H. J. Hemoglobin Riyadh-beta (zero)-thalassemia in an Indian family. Hemoglobin 3: 451-458, 1979. [PubMed: 511584, related citations] [Full Text]

  867. Pirastu, M., del Senno, L., Conconi, F., Vullo, C., Kan, Y. W. Ferrara beta-zero-thalassaemia caused by the beta-39 nonsense mutation. Nature 307: 76, 1984. [PubMed: 6690987, related citations] [Full Text]

  868. Pirastu, M., Galanello, R., Doherty, M. A., Tuveri, T., Cao, A., Kan, Y. W. The same beta-globin gene mutation is present on nine different beta-thalassemia chromosomes in a Sardinian population. Proc. Nat. Acad. Sci. 84: 2882-2885, 1987. [PubMed: 3033668, related citations] [Full Text]

  869. Pirastu, M., Kan, Y. W., Lin, C. C., Baine, R. M., Holbrook, C. T. Hemolytic disease of the newborn caused by a new deletion of the entire beta-globin cluster. J. Clin. Invest. 72: 602-609, 1983. [PubMed: 6308057, related citations] [Full Text]

  870. Pirastu, M., Ristaldi, M. S., Loudianos, G., Murru, S., Sciarratta, G. V., Parodi, M. I., Leone, D., Agosti, S., Cao, A. Molecular analysis of atypical beta-thalassemia heterozygotes. Ann. N.Y. Acad. Sci. 612: 90-97, 1990. [PubMed: 2291578, related citations] [Full Text]

  871. Pisciotta, A. V., Ebbe, S. N., Hinz, J. E. Clinical and laboratory features of two variants of methemoglobin-M disease. J. Lab. Clin. Med. 54: 73-87, 1959. [PubMed: 13665153, related citations]

  872. Pistidda, P., Cherchi, L., Corda, M., Guiso, L., Pardini, S., Pirastru, M., Manca, L., Longinotti, M., Masala, B. Hb Tigraye [beta-79(EF3)asp-his] in a Caucasian family from Sardinia. Hemoglobin 25: 341-345, 2001. [PubMed: 11570729, related citations] [Full Text]

  873. Plaseska, D., de Alarcon, P. A., McMillan, S., Walbrecht, M., Wilson, J. B., Huisman, T. H. J. Hb Iowa or beta119(GH2)gly-to-ala. Hemoglobin 14: 423-429, 1990. [PubMed: 2283296, related citations] [Full Text]

  874. Plaseska, D., Dimovski, A. J., Jankovic, L., Sukarova, E., Efremov, G. D., Gebauer, E., Jerance, D. Hb Hoshida [beta-43(CD2)glu-to-gln] observed in a Yugoslavian family. Hemoglobin 15: 541-543, 1991. [PubMed: 1814859, related citations] [Full Text]

  875. Plaseska, D., Dimovski, A. J., Wilson, J. B., Webber, B. B., Hume, H. A., Huisman, T. H. J. Hb Montreal, a new variant with an extended beta chain due to a deletion of asp, gly, leu at positions 73, 74, and 75, and an insertion of ala, arg, cys, gln at the same location. Blood 77: 178-181, 1991. [PubMed: 1845844, related citations]

  876. Plaseska, D., Jankovic, L., Dimovski, A. J., Milenovic, D., Juricic, D., Efremov, G. D. Hb Yokohama [beta-31(B13)leu-to-pro] detected as a de novo mutation in a Yugoslavian boy. Hemoglobin 15: 469-476, 1991. [PubMed: 1814855, related citations] [Full Text]

  877. Plaseska, D., Wilson, J. B., Gu, L.-H., Kutlar, F., Huisman, T. H. J., Zeng, Y.-T., Shen, M. Hb Zengcheng or beta114(G16)leu-to-met. Hemoglobin 14: 555-557, 1990. [PubMed: 2079435, related citations] [Full Text]

  878. Plaseska-Karanfilska, D., de Weinstein, B. I., Efremov, G. D. Hb Rambam (beta-69(E13)gly-to-asp)/beta-0-thalassemia (codon 5 [-CT]) in a family from Argentina. Hemoglobin 24: 157-161, 2000. [PubMed: 10870889, related citations] [Full Text]

  879. Plaseska-Karanfilska, D., Song, K. S., Efremov, G. D. Hb Old Dominion/Burton-upon-Trent or beta-143(H21)his-to-tyr, found in a diabetic woman from Korea. Hemoglobin 24: 323-326, 2000. [PubMed: 11186263, related citations] [Full Text]

  880. Platt, O. S., Brambilla, D. J., Rosse, W. F., Milner, P. F., Castro, O., Steinberg, M. H., Klug, P. P. Mortality in sickle cell disease: life expectancy and risk factors for early death. New Eng. J. Med. 330: 1639-1644, 1994. [PubMed: 7993409, related citations] [Full Text]

  881. Podda, A., Galanello, R., Maccioni, L., Melis, M. A., Perseu, L., Ruggeri, R., Addis, M., Cao, A. A new unstable hemoglobin variant producing a beta-thalassemia-like phenotype. (Abstract) 3rd International Conference on Thalassemia and the Hemoglobinopathies, Sardinia, April 1989. P. 51.

  882. Podda, A., Galanello, R., Maccioni, L., Melis, M. A., Rosatelli, C., Perseu, L., Cao, A. Hemoglobin Cagliari (beta60 [E4] val-to-glu): a novel unstable thalassemic hemoglobinopathy. Blood 77: 371-375, 1991. [PubMed: 1985702, related citations]

  883. Poncz, M., Ballantine, M., Solowiejczyk, D., Barak, I., Schwartz, E., Surrey, S. Beta-thalassemia in a Kurdish Jew. J. Biol. Chem. 257: 5994-5996, 1982. [PubMed: 7076659, related citations]

  884. Pootrakul, S. N., Wasi, P., Na-Nakorn, S. Haemoglobin J-Bangkok: a clinical, haematological and genetical study. Brit. J. Haemat. 13: 303-309, 1967. [PubMed: 6025242, related citations] [Full Text]

  885. Popp, R. A., Popp, D. M., Shinpock, S. G., Yang, M. Y., Mural, J. G., Aguinaga, M. P., Kopsombut, P., Roa, P. D., Turner, E. A., Rubin, E. M. A transgenic mouse model of hemoglobin S Antilles disease. Blood 89: 4204-4212, 1997. [PubMed: 9166865, related citations]

  886. Powars, D., Schroeder, W. A., Shelton, J. R., Evans, L., Vinetz, R. An individual with hemoglobins S and Deer Lodge. Hemoglobin 1: 97-100, 1977.

  887. Poyart, C., Bursaux, E., Teisseire, B., Freminet, A., Duvelleroy, M., Rosa, J. Hemoglobin Creteil: oxygen transport by erythrocytes: in vitro and in vivo studies in a high oxygen-affinity mutant. Ann. Intern. Med. 88: 758-763, 1978. [PubMed: 27132, related citations] [Full Text]

  888. Poyart, C., Schaad, O., Kister, J., Galacteros, F., Edelstein, S. J., Blouquit, Y., Arous, N. Hemoglobin Saint Mande (beta-102 (G4) asn-to-tyr): functional studies and structural modeling reveal an altered T state. Europ. J. Biochem. 194: 343-348, 1990. [PubMed: 2269272, related citations] [Full Text]

  889. Praxedes, H., Wiltshire, B. G., Lorkin, P. A., Lehmann, H. Cited by Lehmann, H. In: Martin, H.; Nowicki, J. F. (eds.): Int. Symp. 'Synthese, Struktur und Funktion des Hamoglobins,' Bad Nauheim, April, 1972. Munich: Lehmanns (pub.) 1972. Pp. 359-379.

  890. Prchal, J. T., Cashman, D. P., Kan, Y. W. Hemoglobin Long Island is caused by a single mutation (adenine to cytosine) resulting in a failure to cleave amino-terminal methionine. Proc. Nat. Acad. Sci. 83: 24-27, 1986. [PubMed: 3455755, related citations] [Full Text]

  891. Prehu, C., Behnken, L. J., Neumann, R., Riou, J., Kister, J., Kiger, L., Prome, D., Arndt, T., Semmelroggen, B., Schmidt, M., Galacteros, F., Wajcman, H. A new unstable hemoglobin variant with low oxygen affinity: Hb Ilmenau [beta-41(C7)phe-to-cys]. Hemoglobin 26: 169-174, 2002. [PubMed: 12144060, related citations] [Full Text]

  892. Prehu, C., Riou, J., Sartelet, I, Prome, D., Claparols, C., Denier, M., Motte, J., Galacteros, F., Wajcman, H. Hb O-Tibesti [beta-121(GH4)glu-to-lys; beta-11(A8)val-to-ile], a hemoglobin variant carrying in the same beta chain the substitutions of Hb O-Arab and Hb Hamilton, found in combination with Hb S [beta-6(A3)glu-to-val]. Hemoglobin 26: 13-20, 2002. [PubMed: 11939508, related citations] [Full Text]

  893. Premawardhena, A., Fisher, C. A., Fathiu, F., de Silva, S., Perera, W., Peto, T. E. A., Olivieri, N. F., Weatherall, D. J. Genetic determinants of jaundice and gallstones in haemoglobin E beta-thalassemia. Lancet 357: 1945-1946, 2001. [PubMed: 11425418, related citations] [Full Text]

  894. Premawardhena, A., Fisher, C. A., Liu, Y. T., Verma, I. C., de Silva, S., Arambepola, M., Clegg, J. B., Weatherall, D. J. The global distribution of length polymorphisms of the promoters of the glucuronosyltransferase 1 gene (UGT1A1): hematologic and evolutionary implications. Blood Cells Molec. Dis. 31: 98-101, 2003. [PubMed: 12850492, related citations] [Full Text]

  895. Premawardhena, A., Fisher, C. A., Olivieri, N. F., de Silva, S., Arambepola, M., Perera, W., O'Donnell, A., Peto, T. E. A., Viprakasit, V., Merson, L., Muraca, G., Weatherall, D. J. Haemoglobin E beta-thalassemia in Sri Lanka. Lancet 366: 1467-1470, 2005. [PubMed: 16243092, related citations] [Full Text]

  896. Prezant, T. R., Fischel-Ghodsian, N. Trapped-oligonucleotide nucleotide incorporation (TONI) assay, a simple method for screening point mutations. Hum. Mutat. 1: 159-164, 1992. [PubMed: 1301203, related citations] [Full Text]

  897. Pribilla, W., Klesse, P., Betke, K., Lehmann, H., Beale, D. Haemoglobin Koln disease: familial hypochromic hemolytic anemia with hemoglobin anomaly. Klin. Wschr. 43: 1049-1053, 1965. [PubMed: 5881530, related citations] [Full Text]

  898. Pribilla, W. Thalassemie-aehnliche Erkrankung mit neuem minor-Hb (Hb Koln). In: Lehmann, H.; Betke, K.: Haemoglobin-Colloquium. Stuttgart: Georg Thieme Verlag (pub.) 1962. Pp. 1-14.

  899. Price, P. M., Conover, J. H., Hirschhorn, K. Chromosomal localization of human hemoglobin structural genes. Nature 237: 340-342, 1972. [PubMed: 4557400, related citations] [Full Text]

  900. Prior, J. F., Raven, J. L., Wilson, J. B., Kutlar, A., Kutlar, F., Huisman, T. H. J. Hb J-Lome or beta59 (E3) lys-to-asn in a Vietnamese family. Hemoglobin 13: 79-81, 1989. [PubMed: 2703367, related citations] [Full Text]

  901. Proudfoot, N. J., Shander, M. H. M., Manley, J. L., Gefter, M. L., Maniatis, T. Structure and in vitro transcription of human globin genes. Science 209: 1329-1336, 1980. [PubMed: 6158093, related citations] [Full Text]

  902. Puett, D., Paniker, N. V., Lin, K. D., Flexner, J. M., Wasserman, B. K., Krantz, S. B. Hemoglobin Vanderbilt (beta 89 (F5) ser-to-arg): a new hemoglobin mutant with increased oxygen affinity and lowered response to 2,3-diphosphoglycerate. (Abstract) Clin. Res. 25: 53A, 1977.

  903. Qin, W.-B., Pobedimskaya, D. D., Molchanova, T. P., Wilson, J. B., Gu, L.-H., de Pablos, J. M., Huisman, T. H. J. Hb Fannin-Lubbock in five Spanish families is characterized by two mutations: beta-111 GTC-to-CTC (val-to-leu) and beta-119 GGC-to-GAC (gly-to-asp). Hemoglobin 18: 297-306, 1994. [PubMed: 7852084, related citations] [Full Text]

  904. Qualtieri, A., Le Pera, M., Pedace, V., Magariello, A., Brancati, C. Hb Molfetta (beta-126(H4)val-to-leu, GTG-to-CTG): a new, silent, neutral beta chain variant found in an Italian woman. Hemoglobin 26: 7-12, 2002. [PubMed: 11939515, related citations] [Full Text]

  905. Quarum, M., Shih, T., Jones, R. T. Oxygen equilibrium studies of Hb Willamette, beta51(D2)pro-to-arg. Hemoglobin 7: 57-69, 1983. [PubMed: 6841127, related citations] [Full Text]

  906. Quattrin, N., Ventruto, V., De Rosa, L. Hemoglobinopathies in Campania with particular reference to the rare and new types. Blut 20: 292-295, 1970. [PubMed: 5447151, related citations] [Full Text]

  907. Ragusa, A., Lombardo, M., Sortino, G., Lombardo, T., Nagel, R. L., Labie, D. Beta-S gene in Sicily is in linkage disequilibrium with the Benin haplotype: implications for gene flow. Am. J. Hemat. 27: 139-141, 1988. [PubMed: 2893541, related citations] [Full Text]

  908. Rahbar, S., Asmerom, Y., Blume, K. G. A silent hemoglobin variant detected by HPLC: hemoglobin City of Hope beta69 (E13) gly-to-ser. Hemoglobin 8: 333-342, 1984. [PubMed: 6434492, related citations] [Full Text]

  909. Rahbar, S., Beale, D., Isaacs, W. A., Lehmann, H. Abnormal haemoglobins in Iran: observations of a new variant--haemoglobin J Iran (beta 77 his-to-asp). Brit. Med. J. 1: 674-677, 1967. [PubMed: 6019668, related citations] [Full Text]

  910. Rahbar, S., Feagler, R. J., Beutler, E. Hemoglobin Hammersmith, beta 42 (CD1) phe-to-ser, associated with severe hemolytic anemia. Hemoglobin 5: 97-105, 1981. [PubMed: 6259091, related citations] [Full Text]

  911. Rahbar, S., Lee, T., Asmeron, Y. Hb Beckman alpha135 (H13) ala-to-glu: a new unstable variant and reduced oxygen affinity. (Abstract) Blood 78 (suppl. 1): 204a, 1991.

  912. Rahbar, S., Louis, J., Lee, T., Asmerom, Y. Hemoglobin North Chicago (beta36 (C2) proline-to-serine): a new high affinity hemoglobin. Hemoglobin 9: 559-576, 1985. [PubMed: 3937824, related citations] [Full Text]

  913. Rahbar, S., Nowzari, G., Ala, F. Haemoglobin Avicenna (beta47 (CD6) asp-to-ala), a new abnormal haemoglobin. Biochim. Biophys. Acta 576: 466-470, 1979. [PubMed: 427203, related citations] [Full Text]

  914. Rahbar, S., Nowzari, G., Haydari, H., Kaneshmand, P. Hemoglobin Hamadan: beta 56 gly-to-arg. Biochim. Biophys. Acta 379: 645-648, 1975. [PubMed: 1122305, related citations] [Full Text]

  915. Rahbar, S., Rea, C., Blume, K., Seltzer, D., Feiner, R. A second case of hemoglobin McKees Rocks (beta145 tyr-to-term): a variant with premature termination of the beta-chain. Hemoglobin 7: 97-104, 1983. [PubMed: 6841128, related citations] [Full Text]

  916. Rahbar, S., Rosen, R., Nozari, G., Lee, T. D., Asmerom, Y., Wallace, R. B. Hemoglobin Pasadena: identification of the gene mutant by DNA analysis using synthetic DNA probes. Am. J. Hemat. 27: 204-208, 1988. [PubMed: 3348204, related citations] [Full Text]

  917. Rahbar, S., Winkler, K., Louis, J., Rea, C., Blume, K., Beutler, E. Hemoglobin Great Lakes (beta68 (E12) leucine to histidine): a new high-affinity hemoglobin. Blood 58: 813-817, 1981. [PubMed: 7272510, related citations]

  918. Rahbar, S. Haemoglobin D Iran: beta 22 glutamic acid to glutamine (B4). Brit. J. Haemat. 24: 31-36, 1973. [PubMed: 4715135, related citations] [Full Text]

  919. Ramachandran, M., Gu, L.-H., Wilson, J. B., Kitundu, M. N., Adekile, A. D., Liu, J.-C., McKie, K. M., Huisman, T. H. J. A new variant, Hb Muscat [beta32 (B14) leu-to-val] observed in association with Hb S in an Arabian family. Hemoglobin 16: 259-266, 1992. [PubMed: 1517102, related citations] [Full Text]

  920. Ramot, B., Fisher, S., Remez, D., Schneerson, R., Kahane, D., Ager, J. A. M., Lehmann, H. Haemoglobin O in an Arab family: sickle-cell haemoglobin O trait. Brit. Med. J. 2: 1262-1264, 1960. [PubMed: 20788973, related citations] [Full Text]

  921. Ramsay, M., Jenkins, T. Globin gene--associated restriction-fragment-length polymorphisms in Southern African peoples. Am. J. Hum. Genet. 41: 1132-1144, 1987. [PubMed: 2891298, related citations]

  922. Ranney, H. M., Jacobs, A. S., Nagel, R. L. Haemoglobin New York. Nature 213: 876-878, 1967. [PubMed: 6030043, related citations] [Full Text]

  923. Ranney, H. M., Jacobs, A. S., Udem, L., Zalusky, R. Hemoglobin Riverdale-Bronx: an unstable hemoglobin resulting from the substitution of arginine for glycine at helical residue B6 of the beta polypeptide chain. Biochem. Biophys. Res. Commun. 33: 1004-1011, 1968. [PubMed: 5705748, related citations] [Full Text]

  924. Ranney, H. M., Larson, D. L., McCormack, G. H., Jr. Some clinical, biochemical and genetic observations on hemoglobin C. J. Clin. Invest. 32: 1277-1284, 1953. [PubMed: 13108995, related citations] [Full Text]

  925. Reed, C. S., Hampson, R., Gordon, S., Jones, R. T., Novy, M. J., Brimhall, B., Edwards, M. J., Koler, R. D. Erythrocytosis secondary to increased oxygen affinity of a mutant hemoglobin, hemoglobin Kempsey. Blood 31: 623-632, 1968. [PubMed: 5651043, related citations]

  926. Rees, D. C., Duley, J., Simmonds, H. A., Wonke, B., Thein, S. L., Clegg, J. B., Weatherall, D. J. Interaction of hemoglobin E and pyrimidine 5-prime nucleotidase deficiency. Blood 88: 2761-2767, 1996. [PubMed: 8839873, related citations]

  927. Rees, D. C., Rochette, J., Schofield, C., Green, B., Morris, M., Parker, N. E., Sasaki, H., Tanaka, A., Ohba, Y., Clegg, J. B. A novel silent posttranslational mechanism converts methionine to aspartate in hemoglobin Bristol (beta-67(E11) val-met-to-asp). Blood 88: 341-348, 1996. [PubMed: 8704193, related citations]

  928. Reissmann, K. R., Ruth, W. E., Nomura, T. A human hemoglobin with lowered oxygen affinity and impaired heme-heme interactions. J. Clin. Invest. 40: 1826-1833, 1961. [PubMed: 14491349, related citations] [Full Text]

  929. Ren, Y., Chen, S. S., Liang, C. C., Zhang, M. J., Huang, M. X., Zhang, G. L., Zen, X. S. Hb D-Ouled Rabah (beta-19(B1)asn-to-lys): a rare beta-chain variant found in a Chinese family. Hemoglobin 12: 77-79, 1988. [PubMed: 3384702, related citations] [Full Text]

  930. Renda, M., Maggio, A., Warren, T. C., Kazazian, H. H., Jr. Detection of an IVS-1 3-prime end (G-C) beta-thalassemia mutation in the AG invariant dinucleotide of the acceptor splice site in a Sicilian subject. Genomics 13: 234-235, 1992. [PubMed: 1577489, related citations] [Full Text]

  931. Rey, K. S., Unger, C. A., Rao, S. P., Miller, S. T. Sickle cell-hemoglobin E disease: clinical findings and implications. J. Pediat. 119: 949-951, 1991. [PubMed: 1960615, related citations] [Full Text]

  932. Ribeiro, M. L. S., Baysal, E., Kutlar, F., Tamagnini, G. P., Goncalves, P., Lopes, D., Huisman, T. H. J. A novel beta-zero-thalassaemia mutation (codon 15, TGG-to-TGA) is prevalent in a population of central Portugal. Brit. J. Haemat. 80: 567-568, 1992. [PubMed: 1581247, related citations] [Full Text]

  933. Ricco, G., Gallo, E., Pich, P. G., Miniero, R., Mazza, U. Haemoglobin G San Jose in an Italian family. Acta Haemat. 52: 180-188, 1974. [PubMed: 4214182, related citations] [Full Text]

  934. Ricco, G., Pich, P. G., Mazza, U., Rossi, G., Ajmar, F., Arese, P., Gallo, E. Hb J Sicilia: beta 65 (E9) lys-to-asn, a beta homologue of the Hb Zambia. FEBS Lett. 39: 200-204, 1974. [PubMed: 4852224, related citations] [Full Text]

  935. Rieder, R. F., Bradley, T. B., Jr. Hemoglobin Gun Hill: an unstable protein associated with chronic hemolysis. Blood 32: 355-369, 1968. [PubMed: 5675976, related citations]

  936. Rieder, R. F., Oski, F. A., Clegg, J. B. Hemoglobin Philly (beta 35 tyrosine to phenylalanine): studies in the molecular pathology of hemoglobin. J. Clin. Invest. 48: 1627-1642, 1969. [PubMed: 5822575, related citations] [Full Text]

  937. Rieder, R. F., Wolf, D. J., Clegg, J. B., Lee, S. L. Hemoglobin Bushwick, beta 74 (E18) gly-to-val: an unstable hemoglobin found in extremely small amounts. (Abstract) J. Clin. Invest. 53: 65A, 1974.

  938. Rieder, R. F., Zinkham, W. H., Holtzman, N. A. Hemoglobin Zurich: clinical, chemical and kinetic studies. Am. J. Med. 39: 4-20, 1965. [PubMed: 14314237, related citations] [Full Text]

  939. Rihet, P., Flori, L., Tall, F., Traore, A. S., Fumoux, F. Hemoglobin C is associated with reduced Plasmodium falciparum parasitemia and low risk of mild malaria attack. Hum. Molec. Genet. 13: 1-6, 2004. [PubMed: 14613965, related citations] [Full Text]

  940. Ringelhann, B., Konotey-Ahulu, F. I. D., Talapatra, N. C., Nkrumah, F. K., Wiltshire, B. G., Lehmann, H. Haemoglobin K Woolwich (beta 132 lysine-to-glutamine) in Ghana. Acta Haemat. 45: 250-258, 1971. [PubMed: 4999133, related citations] [Full Text]

  941. Ristaldi, M. S., Murru, S., Loudianos, G., Casula, L., Porcu, S., Pigheddu, D., Fanni, B., Sciarratta, G. V., Agosti, S., Parodi, M. I., Leone, D., Camaschella, C., Serra, A., Pirastu, M., Cao, A. The C-T substitution in the distal CACCC box of the beta-globin gene promoter is a common cause of silent beta thalassaemia in the Italian population. Brit. J. Haemat. 74: 480-486, 1990. [PubMed: 2346726, related citations] [Full Text]

  942. River, G. L., Robbins, A. B., Schwartz, S. O. S-C hemoglobin: a clinical study. Blood 18: 385-416, 1961. [PubMed: 14492555, related citations]

  943. Rochette, J., Boissel, J. P., Labie, D., Wajcman, H., Poyart, C., Bohn, B., Varet, B. Polyglobulie par hemoglobine a affinite augmentee: hemoglobine Saint-Jacques beta140 (H18) ala-to-thr, mutant presentant une alteration du site de fixation du 2,3-diphosphoglycerate. Nouv. Rev. Franc. Hemat. 26: 75-77, 1984. [PubMed: 6546989, related citations]

  944. Rochette, J., Poyart, C., Varet, B., Wajcman, H. A new hemoglobin variant altering the beta contact: Hb Chemilly beta99 (G1) asp-to-val. FEBS Lett. 166: 8-12, 1984. [PubMed: 6692925, related citations] [Full Text]

  945. Rodrigues de Souza, L., Kimura, E. M., Albuquerque, D. M., Costa, F. F., de Fatima Sonati, M. Hb Osu-Christiansborg (beta-52(D3)asp-to-asn): a de novo mutation in Brazil. Hemoglobin 28: 65-68, 2004. [PubMed: 15008267, related citations] [Full Text]

  946. Rodriguez Romero, W. E., Castillo, M., Chaves, M. A., Saenz, G. F., Gu, L.-H., Wilson, J. B., Baysal, E., Smetanina, N. S., Leonova, J. Y., Huisman, T. H. J. Hb Costa Rica or alpha-2-beta-2-77(EF1)His-to-Arg: the first example of a somatic cell mutation in a globin gene. Hum. Genet. 97: 829-833, 1996. [PubMed: 8641705, related citations]

  947. Rohe, R. A., Sharma, V. S., Ranney, H. M. Double heterozygosity for beta thalassemia and hemoglobin D Iran (beta 22 glu-to-gln). (Abstract) Meeting of the American Society of Hematology, Hollywood, Florida, December 1972.

  948. Romain, P. L., Schwartz, A. D., Shamsuddin, M., Adams, J. G., III, Mason, R. G., Vida, L. N., Honig, G. R. Hemoglobin J (Chicago) (beta (E20) ala-to-asp): a new hemoglobin variant resulting from substitution of an external residue. Blood 45: 387-393, 1975. [PubMed: 163659, related citations]

  949. Romero, C., Fernandez Fuertes, I., Quintana, A., Blanco, L., Navarro, J. L., Wilson, J. B., Huisman, T. H. J. Hemoglobin G-Szuhu or beta80(EF4)asn-to-lys, in combination with beta-zero-thalassemia in a Spanish family. Hemoglobin 9: 535-539, 1985. [PubMed: 3841346, related citations] [Full Text]

  950. Romero, J. R., Suzuka, S. M., Nagel, R. L., Fabry, M. E. Arginine supplementation of sickle transgenic mice reduces red cell density and Gardos channel activity. Blood 99: 1103-1108, 2002. [PubMed: 11830454, related citations] [Full Text]

  951. Romey, M.-C., Aguilar-Martinez, P., Demaille, J., Claustres, M. Rapid detection of single nucleotide deletions: application to the beta-6 (-A) mutation of the beta-globin gene and to cystic fibrosis. Hum. Genet. 92: 627-628, 1993. [PubMed: 8262525, related citations] [Full Text]

  952. Rooks, H., Bergounioux, J., Game, L., Close, J. P., Osborne, C., Best, S., Senior, T., Height, S., Thompson, R., Hadzic, N., Fraser, P., Bolton-Maggs, P., Thein, S. L. Heterogeneity of the epsilon-gamma-delta-beta-thalassaemias: characterization of three novel English deletions. Brit. J. Haemat. 128: 722-729, 2005. [PubMed: 15725095, related citations] [Full Text]

  953. Ropero, P., Fernandez-Lago, C., Villegas, A., Polo, M., Mateo, M., Mora, A., Gonzalez, F. A. Hb La Coruna (beta-38(C4)thr-to-ile): a new hemoglobin variant leading to familial polycythemia. Hemoglobin 30: 379-383, 2006. [PubMed: 16840229, related citations] [Full Text]

  954. Ropero, P., Villegas, A., Martinez, M., Ataulfo Gonzalez Fernandez, F., Benavente, C., Mateo, M. A deletion of 11 bp (CD 131-134) in exon 3 of the beta-globin gene produces the phenotype of inclusion body beta-thalassemia. Ann. Hemat. 84: 584-587, 2005. [PubMed: 15977037, related citations] [Full Text]

  955. Rosa, J., Labie, D., Wajcman, H., Boigne, J. M., Cabannes, R., Bierme, R., Ruffie, J. Hemoglobin I Toulouse: beta 66 (E10) lys-to-glu: a new abnormal hemoglobin with a mutation localized on the E10 porphyrin surrounding zone. Nature 223: 190-191, 1969. [PubMed: 5791730, related citations] [Full Text]

  956. Rosatelli, C., Leoni, G. B., Tuveri, T., Scalas, M. T., Di Tucci, A., Cao, A. Beta-thalassaemia mutations in Sardinians: implications for prenatal diagnosis. J. Med. Genet. 24: 97-100, 1987. [PubMed: 3031299, related citations] [Full Text]

  957. Rosatelli, M. C., Dozy, A., Faa, V., Meloni, A., Sardu, R., Saba, L., Kan, Y. W., Cao, A. Molecular characterization of beta-thalassemia in the Sardinian population. Am. J. Hum. Genet. 50: 422-426, 1992. [PubMed: 1734721, related citations]

  958. Rotoli, B., Camera, A., Fontana, R., Frigeri, F., Pandolfi, G., Vecchione, R., Poggi, V., Longo, G., Carestia, C., De Angioletti, M., Lacerra, G., Pucci, P., Marino, G., Ferranti, P., Malorni, A., Romano, R., Formisano, S. Hb-M Hyde Park: a de novo mutation, identified by mass spectrometry and DNA analysis. Haematologica 77: 110-118, 1992. [PubMed: 1398295, related citations]

  959. Rouabhi, F., Chardin, P., Boissel, J. P., Beghoul, F., Labie, D., Benabadji, M. Silent beta-thalassemia associated with Hb Knossos beta27(B9) ala-to-ser in Algeria. Hemoglobin 7: 555-561, 1983. [PubMed: 6668188, related citations] [Full Text]

  960. Rousseaux, J., Nuyts, J. P., Demouveau, G., Deutrevaux, M. A severe hemolytic anemia related to a new case of hemoglobin Perth (Abraham Lincoln) in a French patient. Hemoglobin 4: 89-93, 1980. [PubMed: 6153383, related citations] [Full Text]

  961. Rund, D., Cohen, T., Filon, D., Dowling, C. E., Warren, T. C., Barak, I., Rachmilewitz, E., Kazazian, H. H., Jr., Oppenheim, A. Evolution of a genetic disease in an ethnic isolate: beta-thalassemia in the Jews of Kurdistan. Proc. Nat. Acad. Sci. 88: 310-314, 1991. [PubMed: 1986379, related citations] [Full Text]

  962. Rund, D., Dowling, C., Najjar, K., Rachmilewitz, E. A., Kazazian, H. H., Jr., Oppenheim, A. Two mutations in the beta-globin polyadenylation signal reveal extended transcripts and new RNA polyadenylation sites. Proc. Nat. Acad. Sci. 89: 4324-4328, 1992. [PubMed: 1374896, related citations] [Full Text]

  963. Rund, D., Filon, D., Rachmilewitz, E. A., Cohen, T., Dowling, C., Kazazian, H. H., Oppenheim, A. Molecular analysis of beta-thalassemia in Kurdish Jews: novel mutations and expression studies. (Abstract) Blood 74 (suppl. 1): 220a, 1989.

  964. Ruvidic, R., Efremov, G. D., Juricic, D., Rolovic, Z., Pendic, S. Hemoglobin Beograd (alpha (2)-beta (2) 121 glu-to-val) interacting with beta-thalassemia. Acta Haemat. 54: 180-187, 1975. [PubMed: 809962, related citations] [Full Text]

  965. Ryrie, D. R., Plowman, D., Lehmann, H. Haemoglobin Sherwood Forest (beta 104 (G6) arg-to-thr). FEBS Lett. 83: 260-262, 1977. [PubMed: 590504, related citations] [Full Text]

  966. Saba, L., Meloni, A., Sardu, R., Travi, M., Primignani, P., Rosatelli, M. C., Cao, A. A novel beta-thalassemia mutation (G-to-A) at the initiation codon of the beta-globin gene. Hum. Mutat. 1: 420-422, 1992. [PubMed: 1301952, related citations] [Full Text]

  967. Saenz, G. F., Arroyo, G., Montero, G., Lima, F., Martinez, G., Elizondo, J., Jimenez, J. Two cases of hemoglobin New York in Costa Rica. Hemoglobin 4: 101-105, 1980. [PubMed: 7353956, related citations] [Full Text]

  968. Saglio, G., Camaschella, C., Serra, A., Bertero, T., Cambrin, G. R., Guerrasio, A., Mazza, U., Izzo, P., Terragni, F., Giglioni, B., Comi, P., Ottolenghi, S. Italian type of deletional hereditary persistence of fetal hemoglobin. Blood 68: 646-651, 1986. [PubMed: 2427137, related citations]

  969. Saiki, R. K., Bugawan, T. L., Horn, G. T., Mullis, K. B., Erlich, H. A. Analysis of enzymatically amplified beta-globin and HLA-DQ-alpha DNA with allele-specific oligonucleotide probes. Nature 324: 163-166, 1986. [PubMed: 3785382, related citations] [Full Text]

  970. Salhany, J. M. The deoxygenation kinetics of hemoglobin Rainier (beta 145 tyr-to-cys). Biochem. Biophys. Res. Commun. 47: 784-789, 1972. [PubMed: 5026295, related citations] [Full Text]

  971. Salomon, H., Tatarski, I., Dance, N., Huehns, E. R., Shooter, E. M. A new hemoglobin variant found in a Bedouin tribe: hemoglobin 'Rambam'. Isr. J. Med. Sci. 1: 836-840, 1965. [PubMed: 5856126, related citations]

  972. Salzano, A. M., Carbone, V., Pagano, L., Buffardi, S., De Rosa, C., Pucci, P. Hb Vila Real (beta-36(C2)pro-to-his) in Italy: characterization of the amino acid substitution and the DNA mutation. Hemoglobin 26: 21-31, 2002. [PubMed: 11939509, related citations] [Full Text]

  973. Salzano, F. M. Permanence or change? The meaning of genetic variation. Proc. Nat. Acad. Sci. 97: 5317-5321, 2000. [PubMed: 10805790, related citations] [Full Text]

  974. Sammarco, P., Giambona, A., Lo Gioco, P., Di Marzo, R., Maggio, A. Evidence of the African origin of sickle cell hemoglobin in Western Sicily. Hemoglobin 12: 193-196, 1988. [PubMed: 2898460, related citations] [Full Text]

  975. Sanders-Haigh, L., Anderson, W. F., Francke, U. The beta-globin gene is on the short arm of human chromosome 11. Nature 283: 683-686, 1980. [PubMed: 7354859, related citations] [Full Text]

  976. Sansone, G., Carrell, R. W., Lehmann, H. Haemoglobin Genova: beta 28 (B10) leucine to proline. Nature 214: 877-879, 1967. [PubMed: 6054966, related citations] [Full Text]

  977. Sansone, G., Sciarratta, G. V., Genova, R., Darbre, P. D., Lehmann, H. Haemoglobin Shepherds Bush (beta 74(E18) gly-to-asp) in an Italian family. Acta Haemat. 57: 102-108, 1977. [PubMed: 402764, related citations] [Full Text]

  978. Sathiapalan, R., Robinson, M. G. Hereditary haemolytic anaemia due to an abnormal haemoglobin (haemoglobin Kings County). Brit. J. Haemat. 15: 579-587, 1968. [PubMed: 5710064, related citations] [Full Text]

  979. Schiliro, G., Li Volti, S., Musumeci, S., Mollica, F., Marinucci, M., Mavilio, L., Tentori, L. Sicily: a cluster of Hb G-San Jose. Hemoglobin 5: 725-730, 1981. [PubMed: 7338474, related citations] [Full Text]

  980. Schiliro, G., Musumeci, S., Russo, A., Marino, S., Russo, G., Marinucci, M., Fontanarosa, P. P., Tentori, L. Hemoglobin G Copenhagen beta 47 (CD6) asp-to-asn in a Sicilian family. Hemoglobin 5: 195-198, 1981. [PubMed: 7216819, related citations] [Full Text]

  981. Schiliro, G., Russo-Mancuso, G., Dibenedetto, S. P., Samperi, P., Di Cataldo, A., Ragusa, R., Testa, R. Six rare hemoglobin variants found in Sicily. Hemoglobin 15: 431-437, 1991. [PubMed: 1802885, related citations] [Full Text]

  982. Schmidt, R. M., Bechtel, K. C., Johnson, M. H., Therrell, B. L., Jr., Moo-Penn, W. F. Hemoglobin Lufkin: beta 29 (B11) gly-to-asp an unusual hemoglobin variant involving an internal amino acid residue. Hemoglobin 1: 799-814, 1977. [PubMed: 24022, related citations] [Full Text]

  983. Schmidt, R. M., Jue, D. L., Lyonnais, J., Moo-Penn, W. F. Hemoglobin (Bethesda), beta 145 (HC2) tyr-to-his, in a Canadian family. Am. J. Clin. Path. 66: 449-452, 1976. [PubMed: 949044, related citations] [Full Text]

  984. Schnee, J., Aulehla-Scholz, C., Eigel, A., Horst, J. Hb D Los Angeles (D-Punjab) and Hb Presbyterian: analysis of the defect at the DNA level. Hum. Genet. 84: 365-367, 1990. [PubMed: 2307460, related citations] [Full Text]

  985. Schnee, J., Griese, E. U., Eigel, A., Horst, J. Beta-thalassemia gene analysis in a Turkish family reveals a 7 bp deletion in the coding region. (Letter) Blood 73: 2224-2225, 1989. [PubMed: 2730955, related citations]

  986. Schneider, R. G., Alperin, J. B., Brimhall, B., Jones, R. T. Hemoglobin P (beta 117 arg): structure and properties. J. Lab. Clin. Med. 73: 616-622, 1969. [PubMed: 5775133, related citations]

  987. Schneider, R. G., Bremner, J. E., Brimhall, B., Jones, R. T., Shih, T.-B. Hemoglobin Cowtown (beta 146 HC3 his-to-leu): a mutant with high oxygen affinity and erythrocytosis. Am. J. Clin. Path. 72: 1028-1032, 1979. [PubMed: 42311, related citations] [Full Text]

  988. Schneider, R. G., Haggard, M. E., McNutt, C. W., Johnson, J. E., Bowman, B. H., Barnett, D. R. Hemoglobin G Coushatta: a new variant in an American Indian family. Science 143: 697-698, 1964. [PubMed: 14081243, related citations] [Full Text]

  989. Schneider, R. G., Hethig, R. A., Bilunos, M., Brimhall, B. Hemoglobin Baylor (beta 81 leu-to-arg), an unstable mutant with high oxygen affinity. Hemoglobin 1: 85-96, 1977.

  990. Schneider, R. G., Hosty, T. S., Tomlin, G., Atkins, R., Brimhall, B., Jones, R. T. Hb Mobile beta 73(E17) asp-to-val: a new variant. Biochem. Genet. 13: 411-415, 1975. [PubMed: 1180880, related citations] [Full Text]

  991. Schneider, R. G., Ueda, S., Alperin, J. B., Brimhall, B., Jones, R. T. Hemoglobin Sabine at beta 91 (E7) leu-to-pro: an unstable variant causing severe anemia with inclusion bodies. New Eng. J. Med. 280: 739-745, 1969. [PubMed: 5773354, related citations] [Full Text]

  992. Schneider, R. G., Ueda, S., Alperin, J. B., Levin, W. C., Jones, R. T., Brimhall, B. Hemoglobin D Los Angeles in two Caucasian families: hemoglobin SD disease and hemoglobin D thalassemia. Blood 32: 250-259, 1968. [PubMed: 5672850, related citations]

  993. Schneider, R. Personal Communication. Galveston, Tex. 10/6/1978.

  994. Schoenfelder, S., Sexton, T., Chakalova, L., Cope, N. F., Horton, A., Andrews, S., Kurukuti, S., Mitchell, J. A., Umlauf, D., Dimitrova, D. S., Eskiw, C. H., Luo, Y., Wei, C.-L., Ruan, Y., Bieker, J. J., Fraser, P. Preferential associations between co-regulated genes reveal a transcription interactome in erythroid cells. Nature Genet. 42: 53-61, 2010. [PubMed: 20010836, images, related citations] [Full Text]

  995. Schroeder, W. A., Jones, R. T. Some aspects of the chemistry and function of human and animal hemoglobins. Fortschr. Chem. Organ. Naturst. 23: 113-194, 1965.

  996. Schroeder, W. A., Powars, D., Shelton, J. B., Shelton, J. R., Wilson, J. B., Huisman, T. H. J., Bedros, A. A. An unusual phenotypic expression of Hb-Leiden. Biochem. Genet. 20: 1175-1187, 1982. [PubMed: 7165693, related citations] [Full Text]

  997. Schwartz, H. C., Spaet, T. H., Zuelzer, W. W., Neel, J. V., Robinson, A. R., Kaufman, S. F. Combinations of hemoglobin G, hemoglobin S and thalassemia occurring in one family. Blood 12: 238-250, 1957. [PubMed: 13403987, related citations]

  998. Sciarratta, G. V., Ivaldi, G., Moruzzi, F. Hb J-Guantanamo in a Chilean baby. Hemoglobin 14: 115-117, 1990. [PubMed: 2384311, related citations] [Full Text]

  999. Sciarratta, G. V., Ivaldi, G., Sansone, G., Wilson, J. B., Webber, B. B., Huisman, T. H. J. Hb Volga or beta27(B9)ala-to-asp in an Italian family. Hemoglobin 9: 91-93, 1985. [PubMed: 3838977, related citations] [Full Text]

  1000. Sciarratta, G. V., Ivaldi, G. Hb Matera (beta55(D6)met-to-lys): a new unstable hemoglobin variant in an Italian family. Hemoglobin 14: 79-85, 1990. [PubMed: 2384314, related citations] [Full Text]

  1001. Scott, A. F., Phillips, J. A., III, Migeon, B. R. DNA restriction endonuclease analysis for localization of human beta- and delta-globin genes on chromosome 11. Proc. Nat. Acad. Sci. 76: 4563-4565, 1979. [PubMed: 291988, related citations] [Full Text]

  1002. Seid-Akhavan, M., Ayres, M., Salzano, F. M., Winter, W. P., Rucknagel, D. L. Two more examples of Hb Porto Alegre, beta 9 ser-to-cys, in Belem, Brazil. Hum. Hered. 23: 175-181, 1973. [PubMed: 4756855, related citations] [Full Text]

  1003. Serjeant, B., Myerscough, E., Serjeant, G. R., Higgs, D. R., Moo-Penn, W. F. Sickle cell-hemoglobin D Iran: a benign sickle cell syndrome. Hemoglobin 6: 57-59, 1982. [PubMed: 7073867, related citations] [Full Text]

  1004. Serjeant, G. R., Higgs, D. R., Hambleton, I. R. Elderly survivors with homozygous sickle cell disease. (Letter) New Eng. J. Med. 356: 642-643, 2007. [PubMed: 17287491, related citations] [Full Text]

  1005. Serjeant, G. R., Richards, R., Barbor, P. R. H., Milner, P. F. Relatively benign sickle-cell anaemia in 60 patients aged over 30 in the West Indies. Brit. Med. J. 3: 86-91, 1968. [PubMed: 4232783, related citations] [Full Text]

  1006. Shaeffer, J. R., Schmidt, G. J., Kingston, R. E., Bunn, H. F. Synthesis of hemoglobin Cranston, an elongated beta chain variant. J. Molec. Biol. 140: 377-389, 1980. [PubMed: 7441747, related citations] [Full Text]

  1007. Shah, S. C., Malone, J. I., Boissel, J.-P., Kasper, T. J. Hemoglobin South Florida: new variant with normal electrophoretic pattern mistaken for glycosylated hemoglobin. Diabetes 35: 1073-1076, 1986. [PubMed: 3758492, related citations] [Full Text]

  1008. Shalev, O., Boylen, A. L., Levene, C., Oppenheim, A., Rachmilewitz, E. A. Sickle cell trait in a white Jewish family presenting as splenic infarction at high altitude. Am. J. Hemat. 27: 46-48, 1988. [PubMed: 3354556, related citations] [Full Text]

  1009. Sherman, I. J. The sickling phenomenon, with special reference to the difference of sickle cell anemia from the sickle cell trait. Bull. Johns Hopkins Hosp. 67: 309-324, 1940.

  1010. Shibata, S., Iuchi, I., Hamilton, H. B. The first instance of hemoglobin E in a Japanese family. Proc. Jpn. Acad. 40: 846-851, 1962.

  1011. Shibata, S., Iuchi, I., Mazagi, T., Takeda, I. Hemoglobinopathy in Japan. Bull. Yamaguchi Med. Sch. 10: 1-9, 1963.

  1012. Shibata, S., Iuchi, I., Miyaji, T., Ueda, S., Yamashita, K., Suzuno, R. A case of hemolytic disease associated with the production of Heinz bodies and of an abnormal hemoglobin (Hb Ube-1). Med. Biol. 59: 79-84, 1961.

  1013. Shibata, S., Iuchi, I., Miyaji, T., Ueda, S. Spectroscopic characterization of hemoglobin M (Iwate) and hemoglobin M (Kurume), the two variants of hemoglobin M found in Japan. Acta Haemat. Jpn. 24: 477-485, 1961. [PubMed: 13911805, related citations]

  1014. Shibata, S., Iuchi, I., Miyaji, T. Hemoglobin M disease in Japan. Isr. J. Med. Sci. 1: 766-768, 1965. [PubMed: 5856115, related citations]

  1015. Shibata, S., Iuchi, I. Hemoglobin-Hikari (alpha-2-beta-2, T-7): a fast-moving hemoglobin demonstrated in two families of Japanese people, with a brief note on the abnormal hemoglobins of Japan which are likely to be confused with it. (Abstract) Proceedings of the 9th Congress of the International Society of Hematology, Mexico City 1962. Pp. 65-70.

  1016. Shibata, S., Miyaji, T., Iuchi, I., Ohba, Y., Yamamoto, K. Amino acid substitution in hemoglobin M (Akita). J. Biochem. 63: 193-198, 1968. [PubMed: 5669922, related citations] [Full Text]

  1017. Shibata, S., Miyaji, T., Iuchi, I., Ueda, S., Takeda, I. Hemoglobin Hikari (beta 61 asn): a fast-moving hemoglobin found in two unrelated Japanese families. Clin. Chim. Acta 10: 101-105, 1964. [PubMed: 14203236, related citations] [Full Text]

  1018. Shibata, S., Miyaji, T., Iuchi, I., Ueda, S. A comparative study of hemoglobin M (Iwate) and hemoglobin M (Kurume) by means of electrophoresis, chromatography and analysis of peptide chains. Acta Haemat. Jpn. 24: 486-494, 1961. [PubMed: 13911808, related citations]

  1019. Shibata, S., Miyaji, T., Ohba, Y. Abnormal hemoglobins in Japan. Hemoglobin 4: 395-408, 1980. [PubMed: 6998928, related citations] [Full Text]

  1020. Shibata, S., Miyaji, T., Ueda, S., Matsvoka, M., Iuchi, I., Yamada, K., Shinkai, N. Hemoglobin Tochigi (beta 56-59 deleted). A new unstable hemoglobin discovered in a Japanese family. Proc. Jpn. Acad. 46: 440-445, 1970.

  1021. Shih, D. T., Jones, R. T., Shih, M. F.-C., Jones, M. B., Koler, R. D., Howard, J. Hemoglobin Chico (beta66 (E10) lys-to-thr): a new variant with decreased oxygen affinity. Hemoglobin 11: 453-464, 1987. [PubMed: 3429244, related citations] [Full Text]

  1022. Shih, M.-C., Wu, K.-H., Liu, S.-C., Chang, J.-G. Hb Tak: A beta chain elongation at the end of the beta chain, in a Taiwanese. Hemoglobin 29: 65-67, 2005. [PubMed: 15768557, related citations]

  1023. Shimizu, K., Keino, H., Takenaka, O. Hemoglobin Lufkin (beta-29[B11]gly-to-asp) found in a Japanese. Hemoglobin 12: 81-85, 1988. [PubMed: 3384703, related citations] [Full Text]

  1024. Shulman, L. N., Bunn, H. F. Hb Deer Lodge in a Caucasian American: effect of iron deficiency on level of variant. Hemoglobin 12: 197-199, 1988. [PubMed: 3384712, related citations] [Full Text]

  1025. Sick, K., Beale, D., Irvine, D., Lehmann, H., Goodall, P. T., MacDougall, S. Hemoglobin G (Copenhagen) and hemoglobin J (Cambridge): two new beta-chain variants of hemoglobin A. Biochim. Biophys. Acta 140: 231-242, 1967. [PubMed: 6048303, related citations] [Full Text]

  1026. Sierakowska, H., Sambade, M. J., Agrawal, S., Kole, R. Repair of thalassemic human beta-globin mRNA in mammalian cells by antisense oligonucleotides. Proc. Nat. Acad. Sci. 93: 12840-12844, 1996. [PubMed: 8917506, images, related citations] [Full Text]

  1027. Silvestroni, E., Bianco, I., Brancati, C. Haemoglobin P in a family of southern Italian extraction. Nature 200: 658-659, 1963. [PubMed: 14109943, related citations] [Full Text]

  1028. Simonis, M., Klous, P., Splinter, E., Moshkin, Y., Willemsen, R., de Wit, E., van Steensel, B., de Laat, W. Nuclear organization of active and inactive chromatin domains conserved by chromosome conformation capture-on-chip (4C). Nature Genet. 38: 1348-1354, 2006. [PubMed: 17033623, related citations] [Full Text]

  1029. Smetanina, N. S., Gu, L.-H., Rodriguez Romero, W. E., Howard, E. F., Huisman, T. H. J. The relative levels of different types of beta-mRNA and beta-globin in BFU-E derived colonies from patients with beta-chain variants: further evidence for somatic mosaicism in the Hb Costa Rica carrier (beta-77(EF1) his-arg). Hemoglobin 20: 199-212, 1996. [PubMed: 8854130, related citations] [Full Text]

  1030. Smith, E. W., Conley, C. L. Sickle cell-hemoglobin D disease. Ann. Intern. Med. 50: 94-98, 1959. [PubMed: 13617832, related citations] [Full Text]

  1031. Smith, E. W., Krevans, J. R. Clinical manifestations of hemoglobin C disorders. Bull. Johns Hopkins Hosp. 104: 17-43, 1959. [PubMed: 13618691, related citations]

  1032. So, C.-C., Ma, S.-K., Law, K.-M., Chan, A. Y.-Y., Chan, L.-C., Wong, K.-F. Hb Kodaira II: a high oxygen affinity variant with a novel mutation in the beta-globin gene and phenotypic identity to Hb Kodaira. Hemoglobin 26: 205-207, 2002. [PubMed: 12144067, related citations] [Full Text]

  1033. Somjee, S., Yu, L. C., Hagar, A. F., Hempe, J. M. Diagnosis and characterization of Hb C/Hb Iowa: a rare but easily misidentified compound heterozygous condition. Hemoglobin 28: 7-13, 2004. [PubMed: 15008260, related citations] [Full Text]

  1034. Spivak, V. A., Molchanova, T. P., Postnikov, Y. V., Aseeva, E. A., Lutsenko, I. N., Tokarev, Y. N. A new abnormal hemoglobin: Hb Mozhaisk beta92 (F8) his-to-arg. Hemoglobin 6: 169-181, 1982. [PubMed: 7096107, related citations] [Full Text]

  1035. Spivak, V. A. Letter to the editor. (Letter) Hemoglobin 13: 219-220, 1989. [PubMed: 2737920, related citations] [Full Text]

  1036. Spritz, R. A., Jagadeeswaran, P., Choudary, P. V., Biro, P. A., Elder, J. T., deRiel, J. K., Manley, J. L., Gefter, M. L., Forget, B. G., Weissman, S. M. Base substitution in an intervening sequence of a beta-plus-thalassemic human globin gene. Proc. Nat. Acad. Sci. 78: 2455-2459, 1981. [PubMed: 6264477, related citations] [Full Text]

  1037. Spritz, R. A. Duplication-deletion polymorphism 5-prime to the human beta-globin gene. Nucleic Acids Res. 9: 5037-5047, 1981. [PubMed: 7312624, related citations] [Full Text]

  1038. Stabler, S. P., Jones, R. T., Head, C., Shih, D. T.-B., Fairbanks, V. F. Hemoglobin Denver (beta-41 (C7) phe-to-ser): a low-O(2)-affinity variant associated with chronic cyanosis and anemia. Mayo Clin. Proc. 69: 237-243, 1994. [PubMed: 8133661, related citations] [Full Text]

  1039. Stamatoyannopoulos, G., Nute, P. E., Adamson, J. W., Bellingham, A. J., Funk, D. Hemoglobin Olympia (beta 20 valine-to-methionine): an electrophoretically silent variant associated with high oxygen affinity and erythrocytosis. J. Clin. Invest. 52: 342-349, 1973. [PubMed: 4683875, related citations] [Full Text]

  1040. Stamatoyannopoulos, G., Nute, P. E., Giblett, E., Detter, J., Chard, R. Haemoglobin M Hyde Park occurring as a fresh mutation: diagnostic, structural, and genetic considerations. J. Med. Genet. 13: 142-147, 1976. [PubMed: 933112, related citations] [Full Text]

  1041. Stamatoyannopoulos, G., Parer, J. T., Finch, C. A. Physiologic implications of a hemoglobin with decreased oxygen affinity (hemoglobin Seattle). New Eng. J. Med. 281: 915-919, 1969. [PubMed: 5811424, related citations] [Full Text]

  1042. Stamatoyannopoulos, G., Woodson, R., Papayannopoulou, T., Heywood, D., Kurachi, S. Inclusion-body beta-thalassemia trait: a form of beta-thalassemia producing clinical manifestations in simple heterozygotes. New Eng. J. Med. 290: 939-943, 1974. [PubMed: 4361439, related citations] [Full Text]

  1043. Stamatoyannopoulos, G., Yoshida, A., Adamson, J., Heinenberg, S. Hemoglobin Rainier (beta 145 tyrosine to histidine): alkali-resistant hemoglobin with increased oxygen affinity. Science 159: 741-743, 1968. [PubMed: 17795074, related citations] [Full Text]

  1044. Stamatoyannopoulos, G., Yoshida, A. Single chain alkali resistance in hemoglobin Rainier: beta 145 tyrosine to histidine. Science 166: 1005-1006, 1969. [PubMed: 5347519, related citations] [Full Text]

  1045. Steadman, J. H., Yates, A., Huehns, E. R. Idiopathic Heinz body anaemia: Hb Bristol (beta 67 (E 11) val-to-asp). Brit. J. Haemat. 18: 435-446, 1970. [PubMed: 5420592, related citations] [Full Text]

  1046. Steger, H., Eigel, A., Flatz, G., Horst, J. Hemoglobin E and codon 17 nonsense: two beta-globin gene mutations common in Southeast Asia detected by the use of ARMS. Ann. Hemat. 67: 119-120, 1993. [PubMed: 8373896, related citations] [Full Text]

  1047. Steinberg, M. H., Adams, J. G., III, Morrison, W. T., Pullen, D. J., Abney, R., Ibrahim, A., Rieder, R. F. Hemoglobin Mississippi (beta-44 ser-to-cys): studies of the thalassemic phenotype in a mixed heterozygote with beta-plus-thalassemia. J. Clin. Invest. 79: 826-832, 1987. [PubMed: 2434529, related citations] [Full Text]

  1048. Steinberg, M. H., Adams, J. G., III. Thalassemia: recent insights into molecular mechanisms. Am. J. Hemat. 12: 81-92, 1982. [PubMed: 6278929, related citations] [Full Text]

  1049. Steinberg, M. H., Adams, J. G., Thigpen, J. T., Morrison, F. S., Dreiling, J. Hemoglobin Hope (beta 136 gly-to-asp)-S disease: clinical and biochemical studies. J. Lab. Clin. Med. 84: 632-642, 1974. [PubMed: 4283785, related citations]

  1050. Steinberg, M. H., Lovell, W. J., Coleman, M., Dreiling, B. J., Adams, J. G. Hemoglobin Hope: studies of oxygen equilibrium in heterozygotes, hemoglobin S-Hope disease, and isolated hemoglobin Hope. J. Lab. Clin. Med. 88: 125-131, 1976. [PubMed: 932531, related citations]

  1051. Stinson, R. A. Isoelectric focusing studies of a stable asymmetrical hybrid formed with a new hemoglobin variant Hemoglobin Alberta. J. Lab. Clin. Med. 90: 623-631, 1977. [PubMed: 903694, related citations]

  1052. Stinson, R. A. Asymmetric hybrids formed with hemoglobin British Columbia (beta 101 glu-to-lys). Hemoglobin 8: 483-496, 1984. [PubMed: 6500987, related citations] [Full Text]

  1053. Stout, C., Holland, C. K., Bird, R. M. Hemoglobin D in an Oklahoma family. Arch. Intern. Med. 114: 296-300, 1964. [PubMed: 14160125, related citations] [Full Text]

  1054. Strahler, J. R., Rosenbloom, B. B., Hanash, S. M. A silent, neutral substitution detected by reverse-phase high-performance liquid chromatography: hemoglobin Beirut. Science 221: 860-862, 1983. [PubMed: 6879181, related citations] [Full Text]

  1055. Studencki, A. B., Conner, B. J., Impraim, C. C., Teplitz, R. L., Wallace, R. B. Discrimination among the human beta-A, beta-S, and beta-C-globin genes using allele-specific oligonucleotide hybridization probes. Am. J. Hum. Genet. 37: 42-51, 1985. [PubMed: 2983543, related citations]

  1056. Sugihara, J., Imamura, T., Nagafuchi, S., Bonaventura, J., Bonaventura, C., Cashon, R. Hemoglobin Rahere, a human hemoglobin variant with amino acid substitution at the 2,3-diphosphoglycerate binding site: functional consequences of the alteration and effects of bezafibrate on the oxygen bindings. J. Clin. Invest. 76: 1169-1173, 1985. [PubMed: 3930571, related citations] [Full Text]

  1057. Suryantoro, P., Takeshima, Y., Haryanto, A., Matsuo, M. C to T transition at the first nucleotide of codon 63 of the beta-globin gene corresponding to hemoglobin M-Saskatoon in an Indonesian boy. Jpn. J. Hum. Genet. 40: 195-201, 1995. [PubMed: 7663000, related citations] [Full Text]

  1058. Suzuki, Y., Shimizu, T., Sakai, H., Tamaki, M., Koizumi, K., Kuriyama, T., Tsuchida, E., Koseki, H., Shirasawa, T. Model mice for Presbyterian hemoglobinopathy (asn(beta108)-to-lys) confer hemolytic anemia with altered oxygen affinity and instability of Hb. Biochem. Biophys. Res. Commun. 295: 869-876, 2002. [PubMed: 12127975, related citations] [Full Text]

  1059. Sydenstricker, V. P., Horton, B., Payne, R. A., Huisman, T. H. J. Studies on a fast hemoglobin variant found in a Negro family in association with thalassemia. Clin. Chim. Acta 6: 677-685, 1961.

  1060. Tagawa, Y., Fujinami, S., Kadota, Y., Nakagawa, T., Seki, T., Shiozaki, Y., Inoue, K., Harano, T., Harano, K., Ueda, S. Hb Olomouc [beta86(F2)ala-to-asp] found in a Japanese family. Hemoglobin 16: 73-76, 1992. [PubMed: 1634364, related citations] [Full Text]

  1061. Taketa, F., Huang, Y. P., Libnoch, J. A., Dessel, B. H. Hemoglobin Wood beta 97 (FG4) his-to-leu: a new high-oxygen-affinity hemoglobin associated with familial erythrocytosis. Biochim. Biophys. Acta 400: 348-353, 1975. [PubMed: 1164511, related citations]

  1062. Takihara, Y., Nakamura, T., Yamada, H., Takagi, Y., Fukumaki, Y. A novel mutation in the TATA box in a Japanese patient with beta-plus-thalassemia. Blood 67: 547-550, 1986. [PubMed: 3002527, related citations]

  1063. Talbot, D., Collis, P., Antoniou, M., Vidal, M., Grosveld, F., Greaves, D. R. A dominant control region from the human beta-globin locus conferring integration site-independent gene expression. Nature 338: 352-355, 1989. [PubMed: 2922063, related citations] [Full Text]

  1064. Tamagnini, G. P., Lopes, M. C., Castanheira, M. E., Wainscoat, J. S., Wood, W. G. Beta-plus-thalassaemia--Portuguese type: clinical, haematological and molecular studies of a newly defined form of beta-thalassaemia. Brit. J. Haemat. 54: 189-200, 1983. [PubMed: 6189507, related citations] [Full Text]

  1065. Tamagnini, G. P., Ribeiro, M. L., Valente, V., Ramachandran, M., Wilson, J. B., Baysal, E., Gu, L.-H., Huisman, T. H. J. Hb Coimbra or beta-99(G1)asp-to-glu, a newly discovered high oxygen affinity variant. Hemoglobin 15: 487-496, 1991. [PubMed: 1814856, related citations] [Full Text]

  1066. Tanaka, Y., Kelleher, J. F., Schwartz, E., Asakura, T. Oxygen binding and stability properties of Hb Santa Ana (beta88 leu-to-pro). Hemoglobin 9: 157-169, 1985. [PubMed: 3839771, related citations] [Full Text]

  1067. Tatsis, B., Sofroniadou, K., Stergiopoulos, K. Hemoglobin Pyrgos (beta 83 gly-to-asp): a new hemoglobin variant. (Abstract) Meeting of the American Society of Hematology, Hollywood, Florida, December 1972.

  1068. Taylor, J. M., Dozy, A. M., Kan, Y. W., Vermus, H. E., Lie-Injo, L. E., Ganesan, J., Todd, D. Genetic lesion in homozygous thalassaemia (hydrops fetalis). Nature 251: 392-393, 1974. [PubMed: 4424635, related citations] [Full Text]

  1069. Teixeira, A., Tahiri-Alaoui, A., West, S., Thomas, B., Ramadass, A., Martianov, I., Dye, M., James, W., Proudfoot, N. J., Akoulitchev, A. Autocatalytic RNA cleavage in the human beta-globin pre-mRNA promotes transcription termination. Nature 432: 526-530, 2004. [PubMed: 15565159, related citations] [Full Text]

  1070. Tentori, L., Carta Sorcini, M., Buccella, C. Hemoglobin Abruzzo: beta 143 (H 21) his to arg. Clin. Chim. Acta 38: 258-262, 1972. [PubMed: 5031790, related citations] [Full Text]

  1071. Tentori, L. Three examples of double heterozygosis for beta-thalassemia and a rare hemoglobin variant. (Abstract) International Symposium of Hemoglobins and Thalassemia, Istanbul, Turkey 1974.

  1072. Thein, S. L., Best, S., Sharpe, J., Paul, B., Clark, D. J., Brown, M. J. Hemoglobin Chesterfield (beta-28 leu-to-arg) produces the phenotype of inclusion body beta thalassemia. (Letter) Blood 77: 2791-2793, 1991. [PubMed: 1675132, related citations]

  1073. Thein, S. L., Hesketh, C., Taylor, P., Temperley, I. J., Hutchinson, R. M., Old, J. M., Wood, W. G., Clegg, J. B., Weatherall, D. J. Molecular basis for dominantly inherited inclusion body beta-thalassemia. Proc. Nat. Acad. Sci. 87: 3924-3928, 1990. [PubMed: 1971109, related citations] [Full Text]

  1074. Thein, S. L., Hesketh, C., Weatherall, D. J. The molecular basis of beta-thalassemia in UK Asian Indians: applications to prenatal diagnosis. Brit. J. Haemat. 70: 225-231, 1988. [PubMed: 2903765, related citations] [Full Text]

  1075. Thein, S. L., Lynch, J. R., Old, J. M., Weatherall, D. J. Direct detection of haemoglobin E with MnlI. J. Med. Genet. 24: 110-112, 1987. [PubMed: 3031297, related citations] [Full Text]

  1076. Thillet, J., Blouquit, Y., Garel, M. C., Dreyfus, B., Reyes, F., Cohen-Solal, M., Beuzard, Y., Rosa, J. Hemoglobin Creteil beta 89 (F5) ser-to-asn: high oxygen affinity variant of hemoglobin frozen in a quaternary R-structure. J. Molec. Med. 1: 135-150, 1976.

  1077. Thillet, J., Cohen-Solal, M., Seligmann, M., Rosa, J. Functional and physiochemical studies of hemoglobin St. Louis beta 28 (B10) leu-to-gln: a variant with ferric beta heme iron. J. Clin. Invest. 58: 1098-1106, 1976. [PubMed: 186485, related citations] [Full Text]

  1078. Thuret, I., Bardakdjian, J., Badens, C., Wajcman, H., Galacteros, F., Vanuxem, D., Perrimond, H., Giraud, F., Lena-Russo, D. Priapism following splenectomy in an unstable hemoglobin: hemoglobin Olmsted beta-141(H19)leu-to-arg. Am. J. Hemat. 51: 133-136, 1996. [PubMed: 8579053, related citations] [Full Text]

  1079. Tilghman, S. M., Curtis, P. J., Tiemeier, D. C., Leder, P., Weissmann, C. The intervening sequence of a mouse beta-globin gene is transcribed within the 15S beta-globin mRNA precursor. Proc. Nat. Acad. Sci. 75: 1309-1313, 1978. [PubMed: 274720, related citations] [Full Text]

  1080. Todd, D., Chan, V., Schneider, R. G., Dozy, A. M., Kan, Y. W., Chan, T. K. Globin chain synthesis in haemoglobin New York (beta 113 valine-to-glutamic acid). Brit. J. Haemat. 46: 557-564, 1980. [PubMed: 7437334, related citations] [Full Text]

  1081. Tondo, C. V., Salzano, F. M., Rucknagel, D. L. Hemoglobin Porto Alegre, a possible polymer of normal hemoglobin in a Caucasian Brazilian family. Am. J. Hum. Genet. 15: 265-279, 1963. [PubMed: 13985474, related citations]

  1082. Tondo, C. V. Asymmetric tetramer in a second occurrence of hemoglobin Porto Alegre beta 9 ser-to-cys. Hemoglobin 1: 195-210, 1976. [PubMed: 1052181, related citations] [Full Text]

  1083. Tonz, O., Winterhalter, K. H., Glatthaar, B. E. New mutation leading to beta-thalassaemia minor. Nature N.B. 241: 127-128, 1973. [PubMed: 4512457, related citations] [Full Text]

  1084. Townes, T. M., Behringer, R. R. Human globin locus activation region (LAR): role in temporal control. Trends Genet. 6: 219-223, 1990. [PubMed: 2202110, related citations] [Full Text]

  1085. Trabuchet, G., Elion, J., Dunda, O., Lapoumeroulie, C., Ducrocq, R., Nadifi, S., Zohoun, I., Chaventre, A., Carnevale, P., Nagel, R. L., Krishnamoorthy, R., Labie, D. Nucleotide sequence evidence of the unicentric origin of the beta-C mutation in Africa. Hum. Genet. 87: 597-601, 1991. [PubMed: 1680789, related citations] [Full Text]

  1086. Traeger-Synodinos, J., Kanavakis, E., Vrettou, C., Maragoudaki, E., Michael, T. H., Metaxotou-Mavromati, A., Kattamis, C. The triplicated alpha-globin gene locus in beta-thalassemia heterozygotes: clinical, haematological, biosynthetic and molecular studies. Brit. J. Haemat. 95: 467-471, 1996. [PubMed: 8943886, related citations] [Full Text]

  1087. Traeger-Synodinos, J., Tzetis, M., Kanavakis, E., Metaxotou-Mavromati, A., Kattamis, C. The Corfu delta-beta-thalassaemia mutation in Greece: haematological phenotype and prevalence. Brit. J. Haemat. 79: 302-305, 1991. [PubMed: 1720325, related citations] [Full Text]

  1088. Trecartin, R. F., Liebhaber, S. A., Chang, J. C., Lee, Y. W., Kan, Y. W. Beta-zero-thalassemia in Sardinia is caused by a nonsense mutation. J. Clin. Invest. 68: 1012-1017, 1981. [PubMed: 6457059, related citations] [Full Text]

  1089. Treisman, R., Proudfoot, N. J., Shander, M., Maniatis, T. A single base change at a splice site in a beta-0-thalassemia gene causes abnormal RNA splicing. Cell 29: 903-911, 1982. [PubMed: 7151176, related citations] [Full Text]

  1090. Trent, R. J., Harris, M. G., Fleming, P. J., Wyatt, K., Hughes, W. G., Kronenberg, H. Haemoglobin D Punjab: interaction with alpha thalassaemia and diagnosis by gene mapping. Scand. J. Haemat. 32: 275-282, 1984. [PubMed: 6322284, related citations] [Full Text]

  1091. Tsoi, W. C., Li, C. K., Plaseka-Karanfilska, D., Efremov, G. D. Hb Brockton (beta-138(H16)ala-to-pro) observed in a Chinese boy. Hemoglobin 22: 397-400, 1998. [PubMed: 9730372, related citations] [Full Text]

  1092. Tuan, D., Solomon, W., Li, Q., London, I. M. The 'beta-like globin' gene domain in human erythroid cells. Proc. Nat. Acad. Sci. 82: 6384-6388, 1985. [PubMed: 3879975, related citations] [Full Text]

  1093. Tuchinda, S., Beale, D., Lehmann, H. A new haemoglobin in a Thai family: a case of haemoglobin Siriraj-beta thalassaemia. Brit. Med. J. 1: 1583-1585, 1965. [PubMed: 14288126, related citations] [Full Text]

  1094. Turhan, A., Weiss, L. A., Mohandas, N., Coller, B. S., Frenette, P. S. Primary role for adherent leukocytes in sickle cell vascular occlusion: a new paradigm. Proc. Nat. Acad. Sci. 99: 3047-3051, 2002. [PubMed: 11880644, images, related citations] [Full Text]

  1095. Turner, J. W., Jr., Jones, R. T., Brimhall, B., DuVal, M. C., Koler, R. D. Characterization of hemoglobin Burke (beta 107 (G9) gly-to-arg). Biochem. Genet. 14: 577-585, 1976. [PubMed: 10883, related citations] [Full Text]

  1096. Ulukutlu, L., Ozsahin, H., Wilson, J. B., Webber, B. B., Hu, H., Kutlar, A., Kutlar, F., Huisman, T. H. J. HB Brockton (beta138(H16)ala-to-pro) observed in a Turkish girl. Hemoglobin 13: 509-513, 1989. [PubMed: 2599887, related citations] [Full Text]

  1097. van den Berg, H. M., Bruin, M. C. A., Batelaan, D., van Delft, P., van Zwieten, R., Roos, D., Harteveld, C. L., Bernini, L. F., Giordano, P. C. Hb Nijkerk: a new mutation at codons 138/139 of the beta-globin gene inducing severe hemolytic anemia in a Dutch girl. Hemoglobin 23: 135-144, 1999. [PubMed: 10335981, related citations] [Full Text]

  1098. Vassilopoulos, G., Papassotiriou, I., Voskaridou, E., Stamoulakatou, A., Premetis, E., Kister, J., Marden, M., Griffon, N., Poyart, C., Wajcman, H., Galacteros, F., Loukopoulos, D. Hb Arta [beta45(CD4)phe-to-cys]: a new unstable haemoglobin with reduced oxygen affinity in trans with beta-thalassaemia. Brit. J. Haemat. 91: 595-601, 1995. [PubMed: 8555060, related citations] [Full Text]

  1099. Vella, F., Beale, D., Lehmann, H. Haemoglobin O Arab in Sudanese. Nature 209: 308-309, 1966. [PubMed: 5915974, related citations] [Full Text]

  1100. Vella, F., Isaacs, W. A., Lehmann, H. Hemoglobin G (Saskatoon): beta-22-glu-ala. Canad. J. Biochem. 45: 351-353, 1967. [PubMed: 6021187, related citations] [Full Text]

  1101. Vella, F., Lorkin, P. A., Carrell, R. W. A new hemoglobin variant resembling hemoglobin E: hemoglobin E(Saskatoon): beta-22 glu replaced by lys. Canad. J. Biochem. 45: 1385-1391, 1967. [PubMed: 6048388, related citations] [Full Text]

  1102. Ventruto, V., Baglioni, C., De Rosa, L., Bianchi, P., Colombo, B., Quattrin, N. Haemoglobin Caserta: an abnormal haemoglobin observed in a southern Italian family. Scand. J. Haemat. 2: 118-125, 1965. [PubMed: 14343423, related citations] [Full Text]

  1103. Verma, C., Edwards, J. H. Linkage data for the beta-hemoglobin locus. Cytogenet. Cell Genet. 22: 646, 1978. [PubMed: 752559, related citations] [Full Text]

  1104. Vidaud, M., Gattoni, R., Stevenin, J., Vidaud, D., Amselem, S., Chibani, J., Rosa, J., Goossens, M. A 5-prime splice-region G-to-C mutation in exon 1 of the human beta-globin gene inhibits pre-mRNA splicing: a mechanism for beta(+)-thalassemia. Proc. Nat. Acad. Sci. 86: 1041-1045, 1989. [PubMed: 2915972, related citations] [Full Text]

  1105. Villegas, A., Malcorra, J. J., Balda, I., Calero, F., Porres, A., Alvarez-Sala, J. L., Espinos, D. A new Spanish family with Hb Louisville. Am. J. Med. Genet. 32: 9-14, 1989. [PubMed: 2705488, related citations] [Full Text]

  1106. Villegas, A., Martin, G., Wilson, J. B., Webber, B. B., Hu, H., Kutlar, A., Kutlar, F., Huisman, T. H. J. HB Extremadura or beta133(H11)val-to-leu, a new mildly unstable hemoglobin in a Spanish female. Hemoglobin 13: 505-508, 1989. [PubMed: 2599886, related citations] [Full Text]

  1107. Villegas, A., Perez-Clausell, C., Sanchez, J., Sal del Rio, E. A new case of thalassemia intermedia: interaction of a triplicated alpha-globin locus and beta-thalassemia trait. Hemoglobin 16: 99-101, 1992. [PubMed: 1634369, related citations] [Full Text]

  1108. Villegas, A., Ropero, P., Nogales, A., Gonzalez, F. A., Mateo, M., Mazo, E., Rodrigo, E., Arias, M. Hb Santander [beta-34(B16)val-to-asp (GTC-GAC)]: a new unstable variant found as a de novo mutation in a Spanish patient. Hemoglobin 27: 31-35, 2003. [PubMed: 12603091, related citations] [Full Text]

  1109. Villegas, A., Wilson, J. B., Chen, S. S., Calero, F., Reinares, L., Huisman, T. H. J., Espinos, D. Haemoglobin Presbyterian (beta 108 (G10) asn-to-lys) in a Spanish family. Acta Haemat. 76: 161-163, 1986. [PubMed: 3101357, related citations] [Full Text]

  1110. Virshup, D. M., Zinkham, W. H., Sirota, R. L., Caughey, W. S. Unique sensitivity of Hb Zurich to oxidative injury by phenazopyridine: reversal of the effects by elevating carboxyhemoglobin levels in vivo and in vitro. Am. J. Hemat. 14: 315-324, 1983. [PubMed: 6859031, related citations] [Full Text]

  1111. Wada, Y., Ikkala, E., Imai, K., Matsuo, T., Matsuda, H., Lehtinen, M., Hayashi, A., Lehmann, H. Structure and function of a new hemoglobin variant, Hb Meilahti (beta36 (C2) pro-to-thr), characterized by mass spectrometry. Acta Haemat. 78: 109-113, 1987. [PubMed: 3120455, related citations] [Full Text]

  1112. Wade Cohen, P. T., Yates, A., Bellingham, A. J., Huehns, E. R. Amino-acid substitution in the alpha-1-beta-1 intersubunit contact of haemoglobin-Camden (beta 131 (H9) gln-to-glu). (Letter) Nature 243: 467-468, 1973.

  1113. Wade, P. T., Jenkins, T., Huehns, E. R. Haemoglobin variant in a Bushman: haemoglobin D beta-Bushman (16 gly to arg). Nature 216: 688-690, 1967. [PubMed: 6082467, related citations] [Full Text]

  1114. Wajcman, H., Aguilar i Bascompte, J. L., Labie, D., Poyart, C., Bohn, B. Structural and functional studies of hemoglobin Barcelona (beta94 asp-to-his). J. Molec. Biol. 156: 185-202, 1982. [PubMed: 7097767, related citations] [Full Text]

  1115. Wajcman, H., Amegnizin, K. P. E., Belkhodja, O., Labie, D., Kernemp, R. Hemoglobin J (Lome) (beta 59 (E3) lys-to-asn): a new fast moving variant found in a Togolese. FEBS Lett. 84: 372-374, 1977. [PubMed: 598514, related citations] [Full Text]

  1116. Wajcman, H., Baudin-Chich, V., Kister, J., Feo, C., Gombaud-Saintonge, G., Bohn, B., Marden, M., Pagnier, J., Poyart, C., Dode, C., Galacteros, F., Blouquit, Y., Cynober, T., Tchernia, G. Hemoglobin J Guantanamo (beta128 (H6) ala-to-asp) in association with hemoglobin C and alpha-thalassemia in a family from Benin. Am. J. Hemat. 28: 170-175, 1988. [PubMed: 2841847, related citations] [Full Text]

  1117. Wajcman, H., Blouquit, Y., Vasseur, C., Le Querrec, A., Laniece, M., Melevendi, C., Rasore, A., Galacteros, F. Two new human hemoglobin variants caused by unusual mutational events: Hb Zaire contains a five residue repetition within the alpha-chain and Hb Duino has two residues substituted in the beta-chain. Hum. Genet. 89: 676-680, 1992. [PubMed: 1511986, related citations] [Full Text]

  1118. Wajcman, H., Drupt, F., Henthorn, J. S., Kister, J., Prehu, C., Riou, J., Prome, D., Galacteros, F. Two new variants with the same substitution at position beta-122: Hb Bushey [beta-122(GH5)phe-to-leu] and Hb Casablanca [beta-65(E9)lys-to-met; beta-122(GH5)phe-to-leu]. Hemoglobin 24: 125-132, 2000. [PubMed: 10870883, related citations] [Full Text]

  1119. Wajcman, H., Girodon, E., Prome, D., North, M. L., Plassa, F., Duwig, I., Kister, J., Bergerat, J. P., Oberling, F., Lampert, E., Lonsdorfer, J., Goossens, M., Galacteros, F. Germline mosaicism for an alanine to valine substitution at residue beta 140 in hemoglobin Puttelange, a new variant with oxygen affinity. Hum. Genet. 96: 711-716, 1995. [PubMed: 8522332, related citations] [Full Text]

  1120. Wajcman, H., Kilmartin, J. V., Najman, A., Labie, D. Hemoglobin Cochin-Port-Royal: consequences of the replacement of the beta chain C-terminal by an arginine. Biochim. Biophys. Acta 400: 354-364, 1975. [PubMed: 240418, related citations] [Full Text]

  1121. Wajcman, H., Kister, J., M'Rad, A., Prome, D., Milpied, N., Rapp, M. J., Harousseau, J. L., Riou, J., Bardakdjian, J., Galacteros, F. Hb Saint Nazaire (beta-103[G5]phe-to-ile): a new example of polycythemia due to a hemoglobin variant with increased oxygen affinity. Am. J. Hemat. 44: 16-21, 1993. [PubMed: 8342560, related citations] [Full Text]

  1122. Wajcman, H., Kister, J., Marden, M., Bohn, B., Blouquit, Y., Descamps, J., Goudemand, M., Poyart, C., Galacteros, F. Hemoglobin Calais (beta76 (E20) ala-to-pro): a hemoglobin variant with decreased intrinsic oxygen affinity. Biochim. Biophys. Acta 1096: 60-66, 1991.

  1123. Wajcman, H., Kister, J., Prehu, C., Riou, J., Godart, C., Bardakdjian, J., Soummer, A. M., Prome, D., Galacteros, F. Hb Tende [beta-124(H2)pro to leu]: a new variant with a moderate increase in oxygen affinity. Hemoglobin 22: 517-523, 1998. [PubMed: 9859935, related citations] [Full Text]

  1124. Wajcman, H., Kister, J., Prome, D., Galacteros, F., Gilsanz, F. Hb Villaverde [beta-89 (F5) ser-to-thr]: the structural modification of an intrasubunit contact is responsible for a high oxygen affinity. Biochim. Biophys. Acta 1225: 89-94, 1993. [PubMed: 8241293, related citations] [Full Text]

  1125. Wajcman, H., Kister, J., Vasseur, C., Blouquit, Y., Trastour, J. C., Cottenceau, D., Galacteros, F. Structure of the EF corner favors deamidation of asparaginyl residues in hemoglobin: the example of Hb La Roche-sur-Yon [beta 81(EF5)leu to his]. Biochim. Biophys. Acta 1138: 127-132, 1992. [PubMed: 1540659, related citations] [Full Text]

  1126. Wajcman, H., Krishnamoorthy, R., Gacon, G., Elion, J., Allard, C., Labie, D. A new hemoglobin variant involving the distal histidine: Hb Bicetre (beta 63(E7) his-to-pro). J. Molec. Med. 1: 187-197, 1976.

  1127. Wajcman, H., Labie, D., Schapira, G. Hemoglobin Tours: thr beta-87 (F3) deleted and hemoglobin St. Antoine: gly-to-leu beta-74-75 (E18-19) deleted: consequences for oxygen affinity and protein stability. Biochim. Biophys. Acta 295: 495-504, 1973. [PubMed: 4699574, related citations]

  1128. Wajcman, H., Lahary, A., Prome, D., Kister, J., Riou, J., Godart, C., Prehu, C., Traeger-Synodinos, J., Papassotiriou, I., Galacteros, F. Hb Mont Saint Aignan (beta-128(H6)ala-to-pro): a new unstable variant leading to chronic microcytic anemia. Hemoglobin 25: 57-65, 2001. [PubMed: 11300350, related citations] [Full Text]

  1129. Wajcman, H., Mrad, A., Blouquit, Y., Parmentier, C., Riou, J., Galacteros, F. Hemoglobin Villejuif (beta123(H1)thr-to-ile): a new variant found in coincidence with polycythemia vera. Am. J. Hemat. 32: 294-297, 1989. [PubMed: 2816924, related citations] [Full Text]

  1130. Wajcman, H., Riou, J., Prome, D., Kister, J., Galacteros, F. Hb Brie Comte Robert (beta-36(C2)pro-to-ala): a new hemoglobin variant with high oxygen affinity and marked hydrophobic properties. Hemoglobin 23: 281-286, 1999. [PubMed: 10490142, related citations] [Full Text]

  1131. Wajcman, H., Vasseur, C., Blouquit, Y., Santo, D. E., Peres, M. J., Martins, M. C., Poyart, C., Galacteros, F. Hemoglobin Redondo [beta 92(F8) his-to-asn]: an unstable hemoglobin variant associated with heme loss which occurs in two forms. Am. J. Hemat. 38: 194-200, 1991. [PubMed: 1951318, related citations] [Full Text]

  1132. Walker, L., McFarlane, A., Patterson, M., Eng, B., Waye, J. S. Hb Castilla [beta-32(B14)leu-to-arg] caused by a de novo mutation. Hemoglobin 27: 253-256, 2003. [PubMed: 14649317, related citations] [Full Text]

  1133. Watson-Williams, E. J., Beale, D., Irvine, D., Lehmann, H. A new haemoglobin, D Ibadan (beta-87 threonine-to-lysine), producing no sickle-cell haemoglobin D disease with haemoglobin S. Nature 205: 1273-1279, 1965. [PubMed: 14311973, related citations] [Full Text]

  1134. Waye, J. S., Eng, B., Patterson, M., Chui, D. H. K., Fernandes, B. J. Novel beta-0-thalassemia mutation in a Canadian woman of British descent (codons 72/73, -AGTGA, +T). Hemoglobin 21: 385-387, 1997. [PubMed: 9255617, related citations] [Full Text]

  1135. Waye, J. S., Eng, B., Patterson, M., Chui, D. H. K., Fernandes, B. J. Novel beta-thalassemia mutation in patients of Jewish descent: [beta-30(B12)arg-to-gly or IVS-1(-2)(A-to-G)] Hemoglobin 22: 83-85, 1998. [PubMed: 9494053, related citations] [Full Text]

  1136. Waye, J. S., Walker, L., Lafferty, J., Lemire, E. G., Chui, D. H. K. Dominant beta-thalassemia due to a newly identified frameshift mutation in exon 3 (codon 113, GTG to TG). Hemoglobin 26: 83-86, 2002. [PubMed: 11939518, related citations] [Full Text]

  1137. Weatherall, D., Clegg, J. The Thalassemia Syndromes. (4th ed.) Oxford: Blackwell Science (pub.) 2001.

  1138. Weatherall, D. J., Clegg, J. B., Collender, S. T., Wells, R. G. M., Gale, R. E., Huehns, E. R., Perutz, M. F., Viggiano, G., Ho, C. Haemoglobin Radcliffe (beta 99 (G1) ala): a high oxygen-affinity variant causing familial polycythaemia. Brit. J. Haemat. 35: 177-191, 1977. [PubMed: 857849, related citations] [Full Text]

  1139. Weatherall, D. J., Clegg, J. B., Knox-Macaulay, H. H. M., Bunch, C., Hopkins, C. R., Temperley, I. J. A genetically determined disorder with features both of thalassaemia and congenital dyserythropoietic anaemia. Brit. J. Haemat. 24: 681-702, 1973. [PubMed: 4351905, related citations] [Full Text]

  1140. Weatherall, D. J., Clegg, J. B. The Thalassaemia Syndromes. Oxford: Blackwell (pub.) 1981.

  1141. Weatherall, D. J. Hemoglobin J (Baltimore) coexisting in a family with hemoglobin S-I. Bull. Johns Hopkins Hosp. 114: 1-12, 1964. [PubMed: 14117783, related citations]

  1142. Weatherall, D. J. The inherited diseases of hemoglobin are an emerging global health burden. Blood 115: 4331-4336, 2010. [PubMed: 20233970, related citations] [Full Text]

  1143. Weaver, G. A., Rahbar, S., Ellsworth, C. A., de Alarcon, P. A., Forbes, G. B., Beutler, E. Iron overload in three generations of a family with hemoglobin Olympia. Gastroenterology 87: 695-702, 1984. [PubMed: 6745619, related citations]

  1144. Weinstein, B. I., White, J. M., Wiltshire, A., Lehmann, H. Hemoglobina Buenos Aires: una nueva hemoglobina inestable. (Abstract) Medicina 32: 749, 1973.

  1145. Welch, S. G., Bateman, C. Hb D-Neath or beta121 (GH4) glu-to-ala: a new member of the Hb D family. Hemoglobin 17: 255-259, 1993. [PubMed: 8330979, related citations] [Full Text]

  1146. Welch, S. G. Haemoglobin G-Szuhu beta 80 asn-to-lys in an English family. Humangenetik 28: 331-334, 1975. [PubMed: 1176123, related citations] [Full Text]

  1147. Went, L. N., MacIver, J. E. Sickle-cell haemoglobin-J disease. Brit. Med. J. 2: 138-139, 1959. [PubMed: 13843994, related citations] [Full Text]

  1148. Westaway, D., Williamson, R. An intron nucleotide sequence variant in a cloned beta-plus-thalassemia globin gene. Nucleic Acids Res. 9: 1777-1788, 1981. [PubMed: 6264391, related citations] [Full Text]

  1149. White, J. M., Brain, M. C., Lorkin, P. A., Lehmann, H., Smith, M. Mild 'unstable haemoglobin haemolytic anaemia' caused by haemoglobin Shepherds Bush (beta 74 (E18) gly to asp). Nature 225: 939-941, 1970. [PubMed: 5415129, related citations] [Full Text]

  1150. White, J. M., Szur, L., Gillies, I. D. S., Lorkin, P. A., Lehmann, H. Familial polycythaemia caused by a new haemoglobin variant: Hb Heathrow, beta 103 (G5) phenylalanine to leucine. Brit. Med. J. 3: 665-667, 1973. [PubMed: 4742453, related citations] [Full Text]

  1151. Wiedermann, B. F., Indrak, K., Wilson, J. B., Webber, B. B., Yang, K. G., Kutlar, F., Kutlar, A., Huisman, T. H. J. Hb Saint Louis or beta 28 (B10) leu-to-gln in a Czechoslovakian male. Hemoglobin 10: 673-676, 1986. [PubMed: 3557999, related citations] [Full Text]

  1152. Wilkinson, T., Brennan, S. O., Carrell, R. W., Wells, R. M., Como, P., Kronenberg, H. Hemoglobin Summer Hill beta 52(D3) asp-to-his: a new variant from Sydney, Australia. Hemoglobin 4: 185-193, 1980. [PubMed: 7190137, related citations] [Full Text]

  1153. Wilkinson, T., Chua, C. G., Carrell, R. W., Robin, H., Exner, T., Lee, K. M., Kronenberg, H. A new haemoglobin variant, haemoglobin Camperdown (beta 104 (G6) arginine-to-serine), which has normal physiological function. Biochim. Biophys. Acta 393: 195-200, 1975. [PubMed: 1138922, related citations] [Full Text]

  1154. Wilkinson, T., Como, P., Brock, P., Kronenberg, H., Trent, R. J. A., Brennan, S. O. Hemoglobin I High Wycombe in an Australian family. Hemoglobin 11: 51-53, 1987. [PubMed: 3583766, related citations] [Full Text]

  1155. Wilkinson, T., Kronenberg, H., Isaacs, W. A., Lehmann, H. Haemoglobin J Baltimore interacting with beta-thalassaemia in an Australian family. Med. J. Aust. 1: 907-910, 1967. [PubMed: 6026391, related citations] [Full Text]

  1156. Williamson, D., Beresford, C. H., Langdown, J. V., Anderson, C. C., Green, A. R. Polycythaemia associated with homozygosity for the abnormal haemoglobin Sherwood Forest (beta104 (G6)arg-to-thr). Brit. J. Haemat. 86: 890-892, 1994. [PubMed: 7918091, related citations] [Full Text]

  1157. Williamson, D., Brennan, S. O., Carrell, R. W. Hb Brisbane (beta68 (E12) leu-to-his) is unstable. Hemoglobin 7: 473-475, 1983. [PubMed: 6629830, related citations] [Full Text]

  1158. Williamson, D., Brennan, S. O., Muir, H., Carrell, R. W. Hemoglobin Collingwood beta60 (E4) val-to-ala--a new unstable hemoglobin. Hemoglobin 7: 511-519, 1983. [PubMed: 6421773, related citations] [Full Text]

  1159. Williamson, D., Nutkins, J., Rosthoj, S., Brennan, S. O., Williams, D. H., Carrell, R. W. Characterization of Hb Aalborg, a new unstable hemoglobin variant, by fast atom bombardment mass spectrometry. Hemoglobin 14: 137-145, 1990. [PubMed: 2272837, related citations] [Full Text]

  1160. Williamson, D., Perry, D. J., Brown, K., Langdown, J. V., de Silva, C. Compound heterozygosity for two beta chain variants: Hb S (beta6(A3)glu--val) and the high affinity variant Hb San Diego (beta109(G11)val--met). Hemoglobin 19: 27-32, 1995. [PubMed: 7615400, related citations] [Full Text]

  1161. Williamson, D., Wells, R. M. G., Anderson, R., Matthews, J. A new unstable and low oxygen affinity hemoglobin variant: Hb J-Auckland (beta25 (B7) gly-to-asp). Hemoglobin 11: 221-230, 1987. [PubMed: 3654265, related citations] [Full Text]

  1162. Williamson, R., Eskdale, J., Coleman, D. V., Niazi, M., Loeffler, F. E., Modell, B. M. Direct gene analysis of chorionic villi: a possible technique for first-trimester antenatal diagnosis of haemoglobinopathies. Lancet 318: 1125-1127, 1981. Note: Originally Volume II. [PubMed: 6118574, related citations] [Full Text]

  1163. Wilson, C. I. D., Cave, R. J., Lehmann, H., Close, M., Imai, K. Haemoglobin Warwickshire (beta5 (A2) pro-to-arg): a possible 'fine tuning' of 2,3-DPG affinity by beta5 pro (FEBS 1918). FEBS Lett. 176: 331-333, 1984. [PubMed: 6548451, related citations] [Full Text]

  1164. Wilson, G., Forrest, P., Heppinstall, S., Green, B. N., Goodeve, A. C., Peake, I. R., Reilly, J. T., Porter, N., Rees, D. C. A second case of Hb Renert [beta-133(H11)val-ala]. Hemoglobin 25: 337-340, 2001. [PubMed: 11570728, related citations] [Full Text]

  1165. Wilson, J. B., Lam, H., Williams, D., Huisman, T. H. J. Hemoglobin G-San Jose beta 7 (A4) glu-to-gly in a Mexican family. Hemoglobin 4: 95-99, 1980. [PubMed: 7353959, related citations] [Full Text]

  1166. Wilson, J. B., Ramachandran, M., Webber, B. B., Kutlar, F., Hazelwood, L. F., Barnett, D., Hirschler, N. V., Huisman, T. H. J. Hb Cleveland or alpha(2)beta(2)93(F9)cys-to-arg; 121(GH4)glu-to-gln. Hemoglobin 15: 269-278, 1991. [PubMed: 1787096, related citations] [Full Text]

  1167. Wilson, J. B., Webber, B. B., Hu, H., Kutlar, A., Kutlar, F., Codrington, J. F., Prchal, J. T., Hall, K. M., de Pablos, J. M., Rodriguez, I., Huisman, T. H. J. Hemoglobin Birmingham and hemoglobin Galicia: two unstable beta chain variants characterized by small deletions and insertions. Blood 75: 1883-1887, 1990. [PubMed: 2158827, related citations]

  1168. Wilson, J. T., Forget, B. G., Wilson, L. B., Weissman, S. M. Human globin messenger RNA: importance of cloning for structural analysis. Science 196: 200-202, 1977. [PubMed: 847468, related citations] [Full Text]

  1169. Wilson, J. T., Milner, P. F., Summer, M. E., Nallaseth, F. S., Fadel, H. E., Reindollar, R. H., McDonough, P. G., Wilson, L. B. Use of restriction endonucleases for mapping the allele for beta-S-globin. Proc. Nat. Acad. Sci. 79: 3628-3631, 1982. [PubMed: 6285354, related citations] [Full Text]

  1170. Winslow, R. M., Charache, S. Hemoglobin Richmond: subunit dissociation and oxygen equilibrium properties. J. Biol. Chem. 250: 6939-6942, 1975. [PubMed: 239952, related citations]

  1171. Winslow, R. M., Swenberg, M.-L., Gross, E., Chervenick, P., Buchman, R. R., Anderson, W. F. Hemoglobin McKees Rocks (beta 145 tyr-to-term), a human 'nonsense' mutation leading to a shortened beta chain. (Abstract) Am. J. Hum. Genet. 27: 95A, 1975.

  1172. Witkowska, H. E., Lubin, B. H., Beuzard, Y., Baruchel, S., Esseltine, D. W., Vichinsky, E. P., Kleman, K. M., Bardakdjian-Michau, J., Pinkoski, L., Cahn, S., Roitman, E., Green, B. N., Falick, A. M., Shackleton, C. H. L. Sickle cell disease in a patient with sickle cell trait and compound heterozygosity for hemoglobin S and hemoglobin Quebec-Chori. New Eng. J. Med. 325: 1150-1154, 1991. [PubMed: 1891024, related citations] [Full Text]

  1173. Witkowski, J. A. The 51 most-cited articles in the Cold Spring Harbor Symposia on Quantitative Biology. Curr. Contents 33(28): 7-16, 1990.

  1174. Wong, C., Antonarakis, S. E., Goff, S. C., Orkin, S. H., Boehm, C. D., Kazazian, H. H., Jr. On the origin and spread of beta-thalassemia: recurrent observation of four mutations in different ethnic groups. Proc. Nat. Acad. Sci. 83: 6529-6532, 1986. [PubMed: 3462712, related citations] [Full Text]

  1175. Wong, C., Antonarakis, S. E., Goff, S. C., Orkin, S. H., Forget, B. G., Nathan, D. G., Giardina, P. J. V., Kazazian, H. H., Jr. Beta-thalassemia due to two novel nucleotide substitutions in consensus acceptor splice sequences of the beta-globin gene. Blood 73: 914-918, 1989. [PubMed: 2920213, related citations]

  1176. Wong, C., Dowling, C. E., Saiki, R. K., Higuchi, R. G., Erlich, H. A., Kazazian, H. H., Jr. Characterization of beta-thalassaemia mutations using direct genomic sequencing of amplified single copy DNA. Nature 330: 384-386, 1987. [PubMed: 3683554, related citations] [Full Text]

  1177. Wong, S. C., Ali, M. A. M., Lam, H., Webber, B. B., Wilson, J. B., Huisman, T. H. J. Hemoglobin Hamilton or beta11(A8)val-to-ile: a silent beta-chain variant detected by triton X-100 acid-urea polyacrylamide gel electrophoresis. Am. J. Hemat. 16: 47-52, 1984. [PubMed: 6695908, related citations] [Full Text]

  1178. Wong, S. C., Ali, M. A. M., Nicholson, W., Wilson, J. B., Lam, H., Huisman, T. H. J. A second patient with hemoglobin Alberta, a high-oxygen-affinity variant causing erythrocytosis and forming asymmetric tetramers. Hemoglobin 2: 557-559, 1978. [PubMed: 750556, related citations] [Full Text]

  1179. Wong, S. C., Bouver, N., Wilson, J. B., Huisman, T. H. J. Hb J Georgia = Hb J Baltimore = beta16 gly-to-asp. Clin. Chim. Acta 35: 521-522, 1971. [PubMed: 5125343, related citations] [Full Text]

  1180. Wood, E. T., Stover, D. A., Slatkin, M., Nachman, M. W., Hammer, M. F. The beta-globin recombinational hotspot reduces the effects of strong selection around the HbC, a recently arisen mutation providing resistance to malaria. Am. J. Hum. Genet. 77: 637-642, 2005. [PubMed: 16175509, images, related citations] [Full Text]

  1181. Woodson, R. D., Heywood, J. D., Lenfant, C. Oxygen transport in hemoglobin San Francisco. Clin. Res. 18: 134, 1970.

  1182. Worthington, S., Lehmann, H. The first observation of Hb D Punjab beta(0) thalassaemia in an English family with 22 cases of unsuspected beta(0) thalassaemia minor among its members. J. Med. Genet. 22: 377-381, 1985. [PubMed: 4078867, related citations] [Full Text]

  1183. Yamada, H., Hotta, H., Ohba, Y., Miyaji, T., Ito, J., Minami, M. Hemoglobin Pyrgos (beta 83 gly-to-asp) in a Japanese family. Hemoglobin 1: 245-256, 1977. [PubMed: 893127, related citations] [Full Text]

  1184. Yamagishi, Y., Ikeda, K., Takahara, J., Irino, S., Hasui, H., Fujiwara, T., Kaji, Y., Harano, T., Harano, K. Hb J-Guantanamo [beta-128(H6)ala-to-asp] found in a Japanese family. Hemoglobin 17: 379-385, 1993. [PubMed: 8226098, related citations] [Full Text]

  1185. Yamashiro, Y., Hattori, Y., Matsuno, Y., Ohba, Y., Miyaji, T., Yamamoto, K., Yamamoto, K., Nakayama, Y., Abe, Y. Another example of Japanese beta-thalassemia [031 cap (A-to-G)]. Hemoglobin 13: 761-767, 1989. [PubMed: 2634674, related citations] [Full Text]

  1186. Yanase, T., Hanada, M., Seita, M., Ohya, I., Ohta, Y., Imamura, T., Fujimura, T., Kawasaki, K., Yamaoka, K. Molecular basis of morbidity from a series of studies of hemoglobinopathies in western Japan. Jpn. J. Hum. Genet. 13: 40-53, 1968. [PubMed: 5750181, related citations]

  1187. Yang, K. G., Kutlar, F., George, E., Wilson, J. B., Kutlar, A., Stoming, T. A., Gonzalez-Redondo, J. M., Huisman, T. H. J. Molecular characterization of beta-globin gene mutations in Malay patients with Hb E-beta-thalassaemia and thalassaemia major. Brit. J. Haemat. 72: 73-80, 1989. [PubMed: 2736244, related citations] [Full Text]

  1188. Yapo, A. P., Prome, D., Claparols, C., Riou, J., Galacteros, F., Wajcman, H. Hb Yaounde (beta-134(H12)val-to-ala), a new neutral variant found in association with Hb Kenitra (beta-69(E13)gly-to-arg) in a patient from Cameroon. Hemoglobin 25: 97-101, 2001. [PubMed: 11300355, related citations] [Full Text]

  1189. Yeager, A. M., Zinkham, W. H., Jue, D. L., Winslow, R. M., Johnson, M. H., McGuffey, J. E., Moo-Penn, W. F. Hemoglobin Cheverly: an unstable hemoglobin associated with chronic mild anemia. Pediat. Res. 17: 503-507, 1983. [PubMed: 6877904, related citations] [Full Text]

  1190. Yoon, K., Cole-Strauss, A., Kmiec, E. B. Targeted gene correction of episomal DNA in mammalian cells mediated by a chimeric RNA-DNA oligonucleotide. Proc. Nat. Acad. Sci. 93: 2071-2076, 1996. [PubMed: 8700887, related citations] [Full Text]

  1191. Zak, S. J., Brimhall, B., Jones, R. T., Kaplan, M. E. Hemoglobin Andrew-Minneapolis (beta 144 lys-to-asn): a new high-oxygen affinity mutant human hemoglobin. Blood 44: 543-549, 1974. [PubMed: 4413656, related citations]

  1192. Zeng, F., Rodgers, G. P., Huang, S., Schechter, A. N., Salamah, M., Perrine, S., Berg, P. E. Sequence of the -530 region of the beta-globin gene of sickle cell anemia patients with the Arabian haplotype. Hum. Mutat. 3: 163-165, 1994. [PubMed: 8199597, related citations] [Full Text]

  1193. Zeng, Y., Huang, S., Ren, Z., Li, H. Identification of Hb D-Punjab gene: application of DNA amplification in the study of abnormal hemoglobins. Am. J. Hum. Genet. 44: 886-889, 1989. [PubMed: 2729278, related citations]

  1194. Zeng, Y., Huang, S., Tao, Y., Wang, B., Gu, Y., Chen, R. Hemoglobin G-Taipei in three additional Chinese families. Hemoglobin 5: 731-735, 1981. [PubMed: 7338475, related citations] [Full Text]

  1195. Zeng, Y., Huang, S. Hemoglobin New York (beta 113(G15) val-to-glu) in China. Hemoglobin 6: 61-67, 1982. [PubMed: 7068436, related citations]

  1196. Zeng, Y. T., Ren, Z. R., Chen, M. J., Zhao, J. Q., Qiu, X. K., Huang, S. Z. A new unstable haemoglobin variant: Hb Shanghai (beta131(H9)gln-to-pro) found in China. Brit. J. Haemat. 67: 221-223, 1987. [PubMed: 3676109, related citations] [Full Text]

  1197. Zhao, W., Wilson, J. B., Huisman, T. H. J., Sciarratta, G. V., Ivaldi, G., Petrini, C., Ripamonti, M. Hb Camperdown or beta104(G6)arg-to-ser in two Italian males. Hemoglobin 14: 459-461, 1990. [PubMed: 2283301, related citations] [Full Text]

  1198. Zhao, W., Wilson, J. B., Webber, B. B., Huisman, T. H. J., Sciarratta, G. V., Ivaldi, G., Ripamonti, M. A second observation of Hb Abruzzo [beta143(H21)his-to-arg] in an Italian family. Hemoglobin 14: 463-466, 1990. [PubMed: 2283302, related citations] [Full Text]

  1199. Zhu, L. H., Li, M., Wang, S. J. Hemoglobin J-Guantanamo (beta128 (H6) ala-to-asp) found in a Chinese family. Hemoglobin 12: 189-192, 1988. [PubMed: 3384711, related citations] [Full Text]

  1200. Zimmerman, S. A., O'Branski, E. E., Rosse, W. F., Ware, R. E. Hemoglobin S/O(Arab): thirteen new cases and review of the literature. Am. J. Hemat. 60: 279-284, 1999. [PubMed: 10203101, related citations] [Full Text]

  1201. Zinkham, W. H., Houtchens, R. A., Caughey, W. S. Carboxyhemoglobin levels in an unstable hemoglobin disorder (Hb Zurich): effect on phenotypic expression. Science 209: 406-408, 1980. [PubMed: 7384813, related citations] [Full Text]

  1202. Zinkham, W. H., Houtchens, R. A., Caughey, W. S. Relation between variations in the phenotypic expression of an unstable hemoglobin disorder (hemoglobin Zurich) and carboxyhemoglobin levels. Am. J. Med. 74: 23-29, 1983. [PubMed: 6849326, related citations] [Full Text]

  1203. Zinkham, W. H., Liljestrand, J. D., Dixon, S. M., Hutchison, J. L. Observations on the rate and mechanism of hemolysis in individuals with Hb Zurich (His E7 (63) beta-to-arg): II. Thermal denaturation of hemoglobin as a cause of anemia during fever. Johns Hopkins Med. J. 144: 109-116, 1979. [PubMed: 439565, related citations]

  1204. Zinkham, W. H., Vangrov, J. S., Dixon, S. M., Hutchison, J. L. Observations on the rate and mechanism of hemolysis in individuals with Hb Zurich (His E7 (63) beta-to-arg): I. Concentrations of haptoglobin and hemopexin in the serum. Johns Hopkins Med. J. 144: 37-40, 1979. [PubMed: 762915, related citations]


Carol A. Bocchini - updated : 08/23/2023
Kelly A. Przylepa - updated : 08/03/2021
Carol A. Bocchini - updated : 11/14/2019
Cassandra L. Kniffin - updated : 2/14/2013
Cassandra L. Kniffin - updated : 1/22/2013
Ada Hamosh - updated : 11/1/2012
Paul J. Converse - updated : 2/13/2012
Ada Hamosh - updated : 1/4/2012
Paul J. Converse - updated : 11/17/2011
Carol A. Bocchini - updated : 5/20/2011
Ada Hamosh - updated : 9/29/2010
Paul J. Converse - updated : 5/14/2010
Patricia A. Hartz - updated : 1/28/2010
Paul J. Converse - updated : 11/11/2009
Carol A. Bocchini - updated : 5/22/2009
Paul J. Converse - updated : 3/13/2008
Cassandra L. Kniffin - updated : 2/20/2008
George E. Tiller - updated : 1/3/2008
Matthew B. Gross - updated : 7/5/2007
Victor A. McKusick - updated : 2/26/2007
Victor A. McKusick - updated : 11/21/2006
Victor A. McKusick - updated : 10/19/2006
Victor A. McKusick - updated : 9/19/2006
Victor A. McKusick - updated : 3/29/2006
George E. Tiller - updated : 2/17/2006
Victor A. McKusick - updated : 1/30/2006
George E. Tiller - updated : 1/23/2006
Victor A. McKusick - updated : 10/10/2005
Victor A. McKusick - updated : 10/3/2005
Victor A. McKusick - updated : 8/11/2005
Ada Hamosh - updated : 7/27/2005
Victor A. McKusick - updated : 6/20/2005
Victor A. McKusick - updated : 5/11/2005
Victor A. McKusick - updated : 3/7/2005
Victor A. McKusick - updated : 3/3/2005
Ada Hamosh - updated : 2/1/2005
Victor A. McKusick - updated : 12/9/2004
Victor A. McKusick - updated : 12/6/2004
Victor A. McKusick - updated : 10/26/2004
John A. Phillips, III - updated : 9/24/2004
Victor A. McKusick - updated : 9/21/2004
Victor A. McKusick - updated : 8/6/2004
Victor A. McKusick - updated : 6/2/2004
Victor A. McKusick - updated : 2/2/2004
Victor A. McKusick - updated : 1/20/2004
Victor A. McKusick - updated : 1/15/2004
Victor A. McKusick - updated : 4/17/2003
Victor A. McKusick - updated : 3/4/2003
Victor A. McKusick - updated : 3/3/2003
Victor A. McKusick - updated : 11/19/2002
Victor A. McKusick - updated : 10/2/2002
Victor A. McKusick - updated : 9/27/2002
Victor A. McKusick - updated : 9/16/2002
Victor A. McKusick - updated : 8/15/2002
Victor A. McKusick - updated : 6/3/2002
Victor A. McKusick - updated : 5/31/2002
Victor A. McKusick - updated : 5/23/2002
Victor A. McKusick - updated : 4/18/2002
Victor A. McKusick - updated : 4/16/2002
Victor A. McKusick - updated : 4/4/2002
Victor A. McKusick - updated : 2/27/2002
Victor A. McKusick - updated : 1/22/2002
Ada Hamosh - updated : 11/15/2001
Victor A. McKusick - updated : 11/2/2001
Victor A. McKusick - updated : 11/1/2001
Victor A. McKusick - updated : 10/10/2001
Victor A. McKusick - updated : 2/28/2001
Victor A. McKusick - updated : 2/14/2001
Victor A. McKusick - updated : 11/3/2000
Ada Hamosh - updated : 10/19/2000
Victor A. McKusick - updated : 8/31/2000
Victor A. McKusick - updated : 8/16/2000
Victor A. McKusick - updated : 7/21/2000
George E. Tiller - updated : 5/2/2000
Victor A. McKusick - updated : 4/26/2000
Victor A. McKusick - updated : 4/26/2000
Victor A. McKusick - updated : 4/11/2000
Victor A. McKusick - updated : 1/21/2000
Victor A. McKusick - updated : 1/18/2000
Carol A. Bocchini - updated : 12/14/1999
Victor A. McKusick - updated : 12/8/1999
Victor A. McKusick - updated : 9/15/1999
Matthew B. Gross - updated : 8/26/1999
Victor A. McKusick - updated : 8/25/1999
Victor A. McKusick - updated : 8/13/1999
Wilson H. Y. Lo - updated : 8/12/1999
Victor A. McKusick - updated : 7/20/1999
Ada Hamosh - updated : 6/27/1999
Victor A. McKusick - updated : 5/24/1999
Victor A. McKusick - updated : 12/21/1998
Stylianos E. Antonarakis - updated : 12/13/1998
Victor A. McKusick - updated : 11/19/1998
Victor A. McKusick - updated : 8/26/1998
Victor A. McKusick - edited : 8/19/1998
Victor A. McKusick - updated : 4/30/1998
Victor A. McKusick - updated : 3/31/1998
Victor A. McKusick - updated : 2/17/1998
Victor A. McKusick - updated : 11/5/1997
Victor A. McKusick - updated : 9/29/1997
Victor A. McKusick - updated : 9/11/1997
Victor A. McKusick - updated : 8/13/1997
Victor A. McKusick - updated : 5/28/1997
Victor A. McKusick - updated : 2/28/1997
Victor A. McKusick - edited : 2/21/1997
Iosif W. Lurie - updated : 1/17/1997
Moyra Smith - updated : 9/5/1996
Moyra Smith - updated : 8/15/1996
Orest Hurko - updated : 6/13/1995
Creation Date:
Victor A. McKusick : 6/24/1986
alopez : 09/15/2023
carol : 09/15/2023
carol : 08/23/2023
alopez : 07/19/2023
carol : 02/13/2023
carol : 02/10/2023
alopez : 07/07/2022
carol : 03/11/2022
carol : 02/22/2022
carol : 02/21/2022
carol : 12/13/2021
alopez : 08/03/2021
carol : 11/14/2019
alopez : 07/16/2019
alopez : 11/07/2018
carol : 09/24/2018
carol : 07/25/2018
carol : 05/21/2018
carol : 05/10/2018
alopez : 12/12/2017
alopez : 12/11/2017
carol : 04/26/2017
mgross : 03/10/2017
carol : 02/27/2017
joanna : 07/20/2016
carol : 07/19/2016
carol : 07/14/2016
carol : 7/14/2016
carol : 7/12/2016
carol : 7/9/2016
carol : 7/7/2016
carol : 6/23/2016
carol : 6/13/2016
alopez : 4/10/2015
carol : 2/17/2015
carol : 11/10/2014
carol : 11/10/2014
carol : 9/12/2014
joanna : 9/12/2014
terry : 3/14/2013
alopez : 2/20/2013
ckniffin : 2/14/2013
carol : 2/6/2013
ckniffin : 1/22/2013
carol : 12/12/2012
alopez : 11/2/2012
terry : 11/1/2012
alopez : 9/21/2012
terry : 7/6/2012
carol : 2/27/2012
mgross : 2/16/2012
terry : 2/13/2012
alopez : 1/12/2012
terry : 1/4/2012
joanna : 12/20/2011
mgross : 11/17/2011
carol : 6/13/2011
carol : 5/23/2011
carol : 5/20/2011
terry : 5/20/2011
terry : 5/20/2011
terry : 5/20/2011
carol : 5/20/2011
carol : 5/18/2011
terry : 11/3/2010
terry : 10/12/2010
terry : 10/12/2010
alopez : 10/5/2010
terry : 9/29/2010
carol : 8/5/2010
mgross : 5/17/2010
mgross : 5/17/2010
terry : 5/14/2010
wwang : 3/26/2010
alopez : 1/28/2010
carol : 1/8/2010
terry : 12/16/2009
mgross : 12/1/2009
mgross : 12/1/2009
terry : 11/11/2009
wwang : 7/29/2009
carol : 6/3/2009
carol : 5/22/2009
carol : 5/22/2009
terry : 2/4/2009
terry : 1/14/2009
mgross : 3/19/2008
mgross : 3/19/2008
terry : 3/13/2008
wwang : 3/6/2008
ckniffin : 2/20/2008
wwang : 1/11/2008
terry : 1/3/2008
terry : 8/9/2007
mgross : 7/5/2007
alopez : 3/21/2007
terry : 2/26/2007
alopez : 11/27/2006
terry : 11/21/2006
alopez : 10/23/2006
terry : 10/19/2006
wwang : 10/3/2006
terry : 9/19/2006
terry : 6/23/2006
alopez : 5/5/2006
terry : 3/29/2006
wwang : 3/2/2006
terry : 2/17/2006
alopez : 2/7/2006
terry : 1/30/2006
carol : 1/24/2006
wwang : 1/23/2006
carol : 1/19/2006
alopez : 10/10/2005
alopez : 10/7/2005
terry : 10/3/2005
carol : 10/3/2005
carol : 10/3/2005
terry : 9/27/2005
wwang : 8/18/2005
terry : 8/11/2005
terry : 8/3/2005
alopez : 7/28/2005
terry : 7/27/2005
carol : 7/19/2005
alopez : 6/22/2005
terry : 6/20/2005
wwang : 6/7/2005
wwang : 5/12/2005
terry : 5/11/2005
tkritzer : 3/11/2005
terry : 3/7/2005
terry : 3/4/2005
terry : 3/3/2005
tkritzer : 2/1/2005
tkritzer : 1/25/2005
terry : 12/9/2004
terry : 12/6/2004
terry : 11/3/2004
tkritzer : 10/28/2004
terry : 10/26/2004
terry : 10/26/2004
alopez : 9/24/2004
tkritzer : 9/23/2004
terry : 9/21/2004
tkritzer : 8/10/2004
terry : 8/6/2004
tkritzer : 6/8/2004
terry : 6/2/2004
alopez : 5/27/2004
terry : 5/20/2004
tkritzer : 4/7/2004
terry : 4/2/2004
carol : 3/17/2004
tkritzer : 2/2/2004
terry : 2/2/2004
tkritzer : 1/22/2004
terry : 1/20/2004
terry : 1/15/2004
carol : 11/24/2003
alopez : 11/14/2003
alopez : 11/14/2003
alopez : 11/10/2003
cwells : 11/7/2003
carol : 8/25/2003
terry : 7/30/2003
carol : 5/13/2003
carol : 5/13/2003
tkritzer : 4/30/2003
terry : 4/17/2003
carol : 3/11/2003
tkritzer : 3/7/2003
tkritzer : 3/7/2003
terry : 3/4/2003
terry : 3/3/2003
tkritzer : 12/31/2002
tkritzer : 11/27/2002
tkritzer : 11/20/2002
terry : 11/19/2002
tkritzer : 10/7/2002
tkritzer : 10/3/2002
tkritzer : 10/3/2002
tkritzer : 10/3/2002
tkritzer : 10/2/2002
tkritzer : 10/2/2002
carol : 9/27/2002
carol : 9/16/2002
tkritzer : 8/20/2002
tkritzer : 8/16/2002
terry : 8/15/2002
carol : 7/29/2002
alopez : 6/18/2002
terry : 6/3/2002
terry : 5/31/2002
terry : 5/31/2002
alopez : 5/28/2002
terry : 5/23/2002
cwells : 5/1/2002
cwells : 4/24/2002
terry : 4/18/2002
terry : 4/16/2002
cwells : 4/15/2002
cwells : 4/10/2002
terry : 4/4/2002
cwells : 3/22/2002
cwells : 3/20/2002
terry : 2/27/2002
terry : 2/8/2002
carol : 2/5/2002
mcapotos : 1/31/2002
terry : 1/22/2002
alopez : 11/15/2001
terry : 11/15/2001
carol : 11/8/2001
carol : 11/8/2001
mcapotos : 11/2/2001
mcapotos : 11/2/2001
mcapotos : 11/1/2001
mcapotos : 11/1/2001
carol : 10/12/2001
carol : 10/12/2001
terry : 10/10/2001
terry : 2/28/2001
carol : 2/26/2001
terry : 2/26/2001
carol : 2/20/2001
mcapotos : 2/19/2001
mcapotos : 2/16/2001
terry : 2/14/2001
mcapotos : 2/12/2001
mcapotos : 2/12/2001
mcapotos : 1/12/2001
mcapotos : 11/9/2000
terry : 11/3/2000
alopez : 10/19/2000
terry : 9/15/2000
terry : 8/31/2000
carol : 8/29/2000
terry : 8/16/2000
alopez : 7/26/2000
terry : 7/21/2000
terry : 7/21/2000
carol : 6/22/2000
alopez : 5/2/2000
mcapotos : 5/2/2000
mcapotos : 4/28/2000
mcapotos : 4/27/2000
terry : 4/26/2000
terry : 4/26/2000
terry : 4/11/2000
terry : 1/21/2000
mcapotos : 1/20/2000
mgross : 1/19/2000
terry : 1/18/2000
mcapotos : 12/15/1999
carol : 12/14/1999
carol : 12/9/1999
terry : 12/8/1999
carol : 10/5/1999
mgross : 9/22/1999
mgross : 9/21/1999
terry : 9/15/1999
carol : 9/8/1999
carol : 8/26/1999
mgross : 8/26/1999
mgross : 8/25/1999
mgross : 8/13/1999
mgross : 8/12/1999
mgross : 8/12/1999
jlewis : 8/5/1999
terry : 7/20/1999
kayiaros : 7/13/1999
kayiaros : 7/13/1999
carol : 6/27/1999
carol : 5/24/1999
joanna : 5/20/1999
carol : 12/29/1998
terry : 12/21/1998
carol : 12/13/1998
carol : 11/25/1998
terry : 11/19/1998
joanna : 11/19/1998
carol : 8/27/1998
terry : 8/26/1998
terry : 8/19/1998
dkim : 7/24/1998
dkim : 7/21/1998
dkim : 7/21/1998
carol : 6/26/1998
terry : 6/18/1998
terry : 6/18/1998
terry : 6/18/1998
alopez : 6/9/1998
dholmes : 6/8/1998
alopez : 5/14/1998
carol : 5/12/1998
terry : 4/30/1998
alopez : 3/31/1998
terry : 3/24/1998
mark : 3/2/1998
terry : 2/17/1998
jenny : 11/7/1997
terry : 11/5/1997
mark : 10/28/1997
mark : 10/10/1997
jenny : 10/1/1997
terry : 9/29/1997
terry : 9/26/1997
dholmes : 9/26/1997
dholmes : 9/19/1997
jenny : 9/18/1997
terry : 9/11/1997
terry : 9/8/1997
terry : 8/13/1997
joanna : 8/12/1997
terry : 8/6/1997
terry : 8/6/1997
alopez : 7/31/1997
alopez : 7/28/1997
terry : 7/10/1997
alopez : 7/10/1997
mark : 7/10/1997
mark : 7/10/1997
alopez : 7/10/1997
mark : 7/8/1997
mark : 7/8/1997
mark : 7/8/1997
terry : 7/7/1997
jenny : 6/3/1997
terry : 5/28/1997
mark : 2/28/1997
terry : 2/26/1997
mark : 2/21/1997
jamie : 1/17/1997
jamie : 1/15/1997
terry : 1/7/1997
mark : 12/23/1996
terry : 12/18/1996
terry : 12/17/1996
terry : 12/5/1996
terry : 11/18/1996
terry : 11/15/1996
terry : 11/13/1996
terry : 11/5/1996
terry : 10/31/1996
jamie : 10/30/1996
mark : 9/11/1996
mark : 9/5/1996
terry : 9/5/1996
terry : 9/5/1996
marlene : 9/3/1996
mark : 8/15/1996
mark : 7/9/1996
mark : 7/2/1996
terry : 6/25/1996
mark : 6/19/1996
terry : 6/12/1996
terry : 6/5/1996
mark : 4/22/1996
terry : 4/15/1996
mark : 3/30/1996
mark : 3/21/1996
terry : 3/21/1996
mark : 3/11/1996
terry : 2/28/1996
mark : 2/13/1996
terry : 2/5/1996
mark : 1/28/1996
terry : 1/23/1996
mark : 1/10/1996
mark : 1/4/1996
mark : 1/4/1996
mark : 1/4/1996
mark : 11/13/1995
terry : 10/31/1995
davew : 8/25/1994
jason : 7/29/1994
pfoster : 4/5/1994

* 141900

HEMOGLOBIN--BETA LOCUS; HBB


HGNC Approved Gene Symbol: HBB

SNOMEDCT: 127040003, 16360009, 191189009, 191201002, 234392002, 417357006, 65959000, 716682000, 79592006, 86715000, 934007;   ICD10CM: D56.1, D56.2, D56.4, D56.5, D57, D57.1;   ICD9CM: 282.44, 282.45, 282.47, 282.6, 282.60;  


Cytogenetic location: 11p15.4     Genomic coordinates (GRCh38): 11:5,225,464-5,227,071 (from NCBI)


Gene-Phenotype Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
11p15.4 {Malaria, resistance to} 611162 3
Delta-beta thalassemia 141749 Autosomal dominant 3
Erythrocytosis, familial, 6 617980 Autosomal dominant 3
Heinz body anemia 140700 Autosomal dominant 3
Hereditary persistence of fetal hemoglobin 141749 Autosomal dominant 3
Methemoglobinemia, beta type 617971 Autosomal dominant 3
Sickle cell disease 603903 Autosomal recessive 3
Thalassemia-beta, dominant inclusion-body 603902 Autosomal dominant 3
Thalassemia, beta 613985 3

TEXT

Description

The alpha (HBA1, 141800; HBA2, 141850) and beta (HBB) loci determine the structure of the 2 types of polypeptide chains in adult hemoglobin, HbA. Mutant beta globin that sickles causes sickle cell disease (603903). Absence of beta chain causes beta-zero-thalassemia. Reduced amounts of detectable beta globin causes beta-plus-thalassemia. For clinical purposes, beta-thalassemia (613985) is divided into thalassemia major (transfusion dependent), thalassemia intermedia (of intermediate severity), and thalassemia minor (asymptomatic).


Gene Structure

Fine detail of both the mouse (Miller et al., 1978) and the human beta-globin gene was determined in the 1970s (Flavell et al., 1978). The mouse beta-globin gene is interrupted by 2 intervening sequences of DNA that divide it into 3 discontinuous segments. The entire gene, including the coding, intervening and untranslated regions, is transcribed into a colinear 15S mRNA precursor. Because mature globin mRNA is smaller (10S) and does not contain the intervening sequences, the 15S precursor must be processed.

Using restriction endonucleases and recombinant DNA techniques, Flavell et al. (1978) prepared a map of the human beta- and delta- (142000) globin genes. The beta-globin gene contains a nonglobin DNA insert about 800-1000 basepairs in length, present within the sequence coding for amino acids 101-120. A similar untranscribed sequence may be present in the delta gene.


Mapping

Use of a combination of somatic cell hybridization and hybridization of DNA probes permitted assignment of the beta hemoglobin locus to chromosome 11 (Deisseroth et al., 1978). Parallel experiments showed that the gamma globin genes (HBG1, 142200; HBG2, 142250) are also on chromosome 11, a result to be expected from other data indicating linkage of beta and gamma.

Flavell et al. (1978) found that the distance between the beta and delta genes is about 7,000 nucleotide pairs and that the delta gene is to the 5-prime side of the beta gene, as predicted by other evidence. Polymorphism was found at the third nucleotide of the codon for amino acid number 50 (Wilson et al., 1977).

The order of the genes in the beta-globin cluster was proved by restriction enzyme studies (Fritsch et al., 1979); starting with the 5-prime end, the order is gamma-G--gamma-A--delta--beta--Hpa I. By 'liquid' molecular hybridization, Haigh et al. (1979) studied mouse-man hybrid rearrangements involving chromosome 11 and assigned the nonalpha-globin cluster to the region 11p11-p15.

Housman et al. (1979) concluded from study of Chinese-hamster ovary cell lines containing chromosome 11 or selected parts thereof that the beta hemoglobin complex (NAG, nonalpha-globin genes) is in interband p1205-p1208.

Lebo et al. (1981) studied the linkage between 2 restriction polymorphisms, the HpaI polymorphism on the 3-prime side of the beta-globin gene and the SacI polymorphism on the 5-prime side of the insulin gene. They found 4 recombinants in 34 meioses (12%), giving 90% confidence limits for the interval as 6-22 cM.

From in situ hybridization studies, Morton et al. (1984) concluded that the beta-globin gene is situated at 11p15. Their studies included a t(7;11)(q22;p15) in which the beta-globin locus appeared to be at the junction point. Interest relates to the translocation cell line coming from a patient with erythroleukemia and the fact that the ERBB oncogene (131550) is located on chromosome 7 (7pter-q22).

By high-resolution chromosome sorting of human chromosomes carrying segments of chromosome 11 and by spot blotting with various gene-specific probes, Lebo et al. (1985) concluded that the loci for parathyroid hormone, beta-globin, and insulin are all located on 11p15.

By in situ hybridization studies of chromosome 11 rearrangements, Magenis et al. (1985) likewise assigned HBB to 11p15. In an addendum, they referred to studies of a t(7;11) rearrangement that further narrowed the HBB assignment to 11p15.4-11pter.

By high-resolution cytogenetics and in situ hybridization, Lin et al. (1985) placed the beta-globin gene in the 11p15.4-p15.5 segment. Through reanalysis of a Chinese hamster/human cell hybrid that had lost all human chromosomes except 11, Gerhard et al. (1987) reached the conclusion that the beta-globin gene complex is located on 11p15 and that the insulin and HRAS1 genes are located in a segment of DNA approximately 10 Mb long.

Pseudogenes

The eta locus is 1 of 5 ancient beta-related globin genes linked in a cluster, 5-prime--epsilon (142100)--gamma--eta--delta--beta--3-prime, that arose from tandem duplications (Koop et al., 1986). The eta locus was embryonically expressed in early eutherians and persisted as a functional gene in artiodactyls (e.g., goat), but became a pseudogene in proto-primates and was lost from rodents and lagomorphs. Sequence studies show that the goat eta gene is orthologous to the pseudogene located between the gamma and delta loci of primates and called psi-beta-1. (The Hb beta-1 pseudogene (psi-beta-1) can be symbolized HBBP or HBBP1.)


Gene Function

Dye and Proudfoot (2001) performed in vivo analysis of transcriptional termination for the human beta-globin gene and demonstrated cotranscriptional cleavage (CoTC). This primary cleavage event within beta-globin pre-mRNA, downstream of the poly(A) site, is critical for efficient transcriptional termination by RNA polymerase II (see 180660). Teixeira et al. (2004) showed that the CoTC process in the human beta-globin gene involves an RNA self-cleaving activity. They characterized the autocatalytic core of the CoTC ribozyme and showed its functional role in efficient termination in vivo. The identified core CoTC is highly conserved in the 3-prime flanking regions of other primate beta-globin genes. Functionally, it resembles the 3-prime processive, self-cleaving ribozymes described for the protein-encoding genes from the myxomycetes Didymium iridis and Physarum polycephalum, indicating evolutionary conservation of this molecular process. Teixeira et al. (2004) predicted that regulated autocatalytic cleavage elements within pre-mRNAs may be a general phenomenon and that functionally it may provide an entry point for exonucleases involved in mRNA maturation, turnover, and, in particular, transcriptional termination.

It is increasingly appreciated that the spatial organization of DNA in the cell nucleus is a key contributor to genomic function. Simonis et al. (2006) developed 4C technology (chromosome conformation capture (3C)-on-chip), which allowed for an unbiased genomewide search for DNA loci that contact a given locus in the nuclear space. They demonstrated that active and inactive genes are engaged in many long-range interchromosomal interactions and can also form interchromosomal contacts. The active beta-globin locus in the mouse fetal liver preferentially contacts transcribed, but not necessarily tissue-specific, loci elsewhere on chromosome 7, whereas the inactive locus in fetal brain contacts different transcriptionally silent loci. A housekeeping gene in a gene-dense region on chromosome 8 of the mouse, Rad23a (600061), formed long-range contacts predominantly with other active gene clusters, both in cis and in trans, and many of these intra- and interchromosomal interactions were conserved between the tissues analyzed. The data demonstrated that chromosomes fold into areas of active chromatin and areas of inactive chromatin and established 4C technology as a powerful tool to study nuclear architecture.

Schoenfelder et al. (2010) found that mouse Hbb and Hba associated with hundreds of active genes from nearly all chromosomes in nuclear foci that they called 'transcription factories.' The 2 globin genes preferentially associated with a specific and partially overlapping subset of active genes. Schoenfelder et al. (2010) also noted that expression of the Hbb locus is dependent upon Klf1 (600599), while expression of the Hba locus is only partially dependent on Klf1. Immunofluorescence analysis of mouse erythroid cells showed that most Klf1 localized to the cytoplasm and nuclear Klf1 was present in discrete sites that overlapped with RNAII foci. Klf1 knockout in mouse erythroid cells specifically disrupted the association of Klf1-regulated genes within the Hbb-associated network. Klf1 knockout more weakly disrupted interactions within the specific Hba network. Schoenfelder et al. (2010) concluded that transcriptional regulation involves a complex 3-dimensional network rather than factors acting on single genes in isolation.


Biochemical Features

Crystal Structure

Andersen et al. (2012) presented the crystal structure of the dimeric porcine haptoglobin (140100)-hemoglobin complex determined at 2.9-angstrom resolution. This structure revealed that haptoglobin molecules dimerize through an unexpected beta-strand swap between 2 complement control protein (CCP) domains, defining a new fusion CCP domain structure. The haptoglobin serine protease domain forms extensive interactions with both the alpha- and beta-subunits of hemoglobin, explaining the tight binding between haptoglobin and hemoglobin. The hemoglobin-interacting region in the alpha-beta dimer is highly overlapping with the interface between the 2 alpha-beta dimers that constitute the native hemoglobin tetramer. Several hemoglobin residues prone to oxidative modification after exposure to heme-induced reactive oxygen species are buried in the haptoglobin-hemoglobin interface, thus showing a direct protective role of haptoglobin. The haptoglobin loop previously shown to be essential for binding of haptoglobin-hemoglobin to the macrophage scavenger receptor CD163 (605545) protrudes from the surface of the distal end of the complex, adjacent to the associated hemoglobin alpha-subunit. Small-angle x-ray scattering measurements of human haptoglobin-hemoglobin bound to the ligand-binding fragment of CD163 confirmed receptor binding in this area, and showed that the rigid dimeric complex can bind 2 receptors.


Molecular Genetics

Beta-Thalassemias

The beta-thalassemias were among the first human genetic diseases to be examined by means of new techniques of recombinant DNA analysis. In general, the molecular pathology of disorders resulting from mutations in the nonalpha-globin gene region is the best known, this elucidation having started with sickle cell anemia in the late 1940s. Steinberg and Adams (1982) reviewed the molecular defects identified in thalassemias: (1) gene deletion, e.g., of the terminal portion of the beta gene (Orkin et al., 1979); (2) chain termination (nonsense) mutations (Chang and Kan, 1979; Trecartin et al., 1981); (3) point mutation in an intervening sequence (Spritz et al., 1981; Westaway and Williamson, 1981); (4) point mutation at an intervening sequence splice junction (Baird et al., 1981); (5) frameshift deletion (Orkin and Goff, 1981); (6) fusion genes, e.g., the hemoglobins Lepore; and (7) single amino acid mutation leading to very unstable globin, e.g., Hb Vicksburg (beta leu75-to-ter).

Since it had been shown by cDNA-DNA hybridization that some cases of severe alpha-thalassemia result from deletion of all or most of the alpha globin genes, Ottolenghi et al. (1975) applied similar techniques to a study of whether beta genes were present in the forms of beta-thalassemia with no synthesis of beta chains. They studied material from persons heterozygous for beta-zero-thalassemia and delta-beta-thalassemia and concluded that at least one of the haploid genomes in this patient had a substantially intact beta globin gene. The beta globin structural gene is intact in beta-zero-thalassemia (Kan et al., 1975) but deleted in both hereditary persistence of fetal hemoglobin (Kan et al., 1975) and delta-beta-thalassemia (Ottolenghi et al., 1975); see 141749.

The possibility that the genetic lesions in beta-plus-thalassemia lie at splicing sites within intervening sequences of the beta globin gene was discussed by Maquat et al. (1980). Beta-zero-thalassemia is heterogeneous. Some cases have absent beta-globin mRNA. Some have a structurally abnormal beta-globin mRNA, usually in reduced amounts. Baird et al. (1981) found a nucleotide change at the splice junction at the 5-prime end of the large intervening sequence (IVS2) as the defect in 3 cases (1 Italian; 2 Iranian).

In a family of Scottish-Irish descent, Pirastu et al. (1983) studied a new type of gamma-delta-beta thalassemia. The proposita presented with hemolytic disease of the newborn which was characterized by microcytic anemia. Initial restriction enzyme analysis showed no grossly abnormal pattern, but studies of polymorphic restriction sites and gene dosage showed extensive deletion of the entire beta-globin cluster. In situ hybridization with radioactive beta-globin gene probes showed that only one 11p homolog contained the beta-globin gene cluster. Kazazian et al. (1982) observed a similar extensive deletion in a Mexican family.

Cai and Kan (1990) demonstrated the usefulness of denaturing gradient gel electrophoresis for detecting beta-thalassemia mutations and suggested that it might be a useful nonradioactive means of detecting mutations in other genetic disorders. Other methods are hybridization with allele-specific oligonucleotide probes, ribonuclease or chemical cleavage, and restriction endonuclease analysis. PCR greatly facilitated implementation of all these detection methods.

Matsuno et al. (1992) invoked possible gene conversion at the chi sequence near the 5-prime end of exon 2 (codons 31-34) as the explanation for the finding of a beta-thalassemia mutation common in southeast Asia (frameshift mutation in codons 41 and 42; see 141900.0326), as well as in Japan, on 2 different restriction frameworks (haplotypes). They presumed that the 6 families found in Japan with this particular mutation had inherited it from ancestors who had migrated to Japan from southeast Asia.

By analysis of family data on 15 restriction site polymorphisms (RSPs), Chakravarti et al. (1984) identified a 'hotspot' for meiotic recombination at the 5-prime end of the beta gene. Recombination leftward (in the 5-prime direction) from a point called chi near the end of the beta-globin gene is 3 to 30 times the expected rate; in the use of RSPs in prenatal diagnosis, it had been assumed that a marker 10 kb from a mutant gene would recombine at a rate of 10(-5) per kb, leading to a diagnostic error of 1 in 10,000. However, their data suggested the error rate using 'loci' on opposite sides of chi may be as high as 1 in 312. By a computer search of the DNA sequences of the beta cluster, they located a chi sequence (5-prime-GCTGGTGG-3-prime) at the 5-prime end of the second intervening sequence of the beta gene. This chi sequence, a promoter of generalized recombination in lambda phage, has been found in high frequency in the mouse genome, especially in immunoglobulin DNA. A recombinational hotspot has been found in the mouse major histocompatibility complex.

In a large Amish pedigree, Gerhard et al. (1984) observed an apparent crossover within the beta-globin gene cluster in the region of the recombinational 'hotspot' postulated by Chakravarti et al. (1984) on the basis of linkage disequilibrium in population data. It was also possible to identify the orientation of the beta-globin cluster vis-a-vis the centromere: cen--5-prime--epsilon--beta--3-prime--pter.

Camaschella et al. (1988) identified recombination between 2 paternal chromosomes in a region 5-prime to the beta gene, previously indicated to contain a 'hotspot' for recombination. The recombination was identified because in the course of prenatal diagnosis by linkage to RFLPs, a homozygous beta-thalassemia fetus was misdiagnosed as beta-thalassemia trait.

In the course of studying an Irish family with beta-thalassemia due to the Q39X mutation in the HBB gene (141900.0312), Hall et al. (1993) found a fourth case of recombination in the beta-globin gene cluster. The event had occurred 5-prime of the polymorphic RsaI site at position -550 bp upstream of the beta-globin gene mRNA cap site, within the 9.1-kb region shown to be a hotspot for recombination.

Huang et al. (1986) reported the same 'TATA' box mutation leading to the same nondeletion form of beta-thalassemia in Chinese as had been reported in American blacks by Antonarakis et al. (1984); see 141900.0379. There are other illustrations indicating that mutations in the beta-globin gene can recur.

Orkin et al. (1982) developed and applied a new strategy for the comprehensive analysis of existing mutations in a class of human disease. They combined analysis of various restriction enzyme polymorphisms in the beta-globin gene cluster with direct examination of beta-globin structural genes in Mediterranean persons with beta-thalassemia. The approach was prompted by the finding that specific mutant genes are strongly linked to patterns of restriction site polymorphism (haplotypes) in this region of the genome. They isolated 8 different mutant genes among the 9 different haplotypes represented in Mediterraneans. Seven of the 8 genes were present in Italians from various locales in Italy, and 6 in Greeks. Several were previously unknown mutations, and 1 of these possibly affects transcription. The strategy is probably applicable to the analysis of heterogeneity in other diseases of single-copy genes. When linkage analysis can be performed in the family, the haplotype analysis will be highly useful in prenatal diagnosis of beta-thalassemia. Indeed, the method of haplotyping proved highly useful both in tracing the origin of mutations and in family studies (see Antonarakis et al., 1982). Losekoot et al. (1992) described a method for rapid detection of beta-globin haplotypes (referred to by them as framework) by denaturing gradient gel electrophoresis.

Rosatelli et al. (1987) analyzed the molecular defect in 494 Sardinian beta-thalassemia heterozygotes. The most prevalent mutation, accounting for 95.4% of cases, was the nonsense mutation at codon 39 (141900.0312). The remainder, in decreasing order of frequency, were a frameshift at codon 6 (2.2%), beta-plus IVS1, nucleotide 110 (0.4%), and beta-plus IVS2, nucleotide 745 (0.4%). The DNA sequences along the human beta-globin cluster are highly polymorphic; over 20 polymorphic restriction endonuclease sites have been described in this 60-kb region. RFLP haplotypes have been useful in defining various thalassemia lesions, such as deletions, for prenatal diagnosis of beta-thalassemia, and for tracing the origin and migration of mutant genes.

Pirastu et al. (1987) found that the predominant beta-thalassemia in Sardinia, the beta-zero type due to nonsense mutation (CAG-to-TAG) at beta-39 (141900.0312), resides on 9 different chromosome haplotypes. One of the haplotypes included a cytosine-to-thymine point mutation 196 nucleotides upstream from the A-gamma-globin gene (142200.0027). The gamma-A mutation at position -196 is associated with high levels of production of fetal hemoglobin. The beta-39 nonsense mutation may have gotten onto the -196 chromosome through crossing-over. A chromosome carrying such a double mutation could be expected to impart selective advantage because the beta-thalassemia would protect against malaria while the increased gamma-globin production would ameliorate the severity of the beta-thalassemia. A similar mechanism may have been operative in the case of another haplotype which combined the beta-39 nonsense mutation with triple gamma loci produced by the addition of a second G-gamma-globin gene. Pirastu et al. (1987) proposed a schema by which the findings were explained by a single initial mutation with subsequent crossovers between the 5-prime and 3-prime blocks of genes producing 6 other chromosomes and then the creation of 2 others by crossing-over and gene conversion. Additional diversity could have arisen through other beta-39 mutations. The mutation identified in a family of northern European origin by Chehab et al. (1986) was of this type.

Direct sequencing of specific regions of genomic DNA became feasible with the invention of PCR, which permits amplification of specific regions of DNA (Church and Gilbert, 1984; Saiki et al., 1986). For example, Wong et al. (1986) amplified human mitochondrial DNA and sequenced it directly. Wong et al. (1987) applied a combination of PCR and direct sequence analysis of the amplified product to the study of beta-thalassemia in 5 patients whose mutant alleles had not been characterized. They found 2 previously undescribed mutations along with 3 previously known ones. One new allele was a frameshift at codons 106-107 and the other was an A-to-C transversion at the cap site (+1) of the beta-globin gene. The latter was the first natural mutation observed at the cap site (141900.0387).

In a study of beta-thalassemia in Spain, Amselem et al. (1988) demonstrated the usefulness of the dot-blot hybridization of PCR-amplified genomic DNA in both rapid population surveys and prenatal diagnosis. They found 7 different beta-thalassemia mutations. The nonsense codon 39 accounted for 64%, whereas the IVS1 position 110 mutation (141900.0364), the most common cause of beta-thalassemia in the eastern part of the Mediterranean basin, was underrepresented (8.5%). The IVS1 mutation at position 6 (141900.0360) accounted for 15% of the defects and led to a more severe form of beta(+)-thalassemia than originally described in most patients with this mutation.

Diaz-Chico et al. (1988) described 2 families, 1 Yugoslavian and 1 Canadian, with heterozygous thalassemia characterized by mild anemia with severe microcytosis and hypochromia, normal levels of hemoglobin A(2), and slightly raised hemoglobin F levels. In both families the condition resulted from large deletions which included all functional and pseudogenes of the beta-globin gene cluster. The deletion was at least 148 kb in the Yugoslavian family and 185 kb in the Canadian family.

Aulehla-Scholz et al. (1989) described a deletion comprising about 300 basepairs in a female heterozygote, resulting in loss of exon 1, part of IVS1, and the 5-prime beta-globin gene promoter region.

Laig et al. (1989) identified new beta-thalassemia mutations in northern and northeastern Thailand.

Rund et al. (1991) studied beta-thalassemia among Kurdistan Jews. They identified 13 distinct mutations among 42 sibships, of which 3 were previously undescribed. Four of the mutations (see 141900.0331, 141900.0341, 141900.0373, 141900.0383) were unique to Kurdish Jews and two-thirds of the mutant chromosomes carried the mutations unique to Kurdish Jews. Haplotype and geographic analyses suggested that thalassemia in central Kurdistan has evolved from multiple mutational events. Genetic admixture with the local population appears to be the primary mechanism of the evolution of thalassemia in Turkish Kurdistan, whereas there is evidence for a founder effect in Iranian Kurdistan.

Huang et al. (1990) used DNA from dried blood specimens amplified by PCR to study the distribution of beta-thalassemia mutations in southern, western, and eastern China.

As indicated by the work of Villegas et al. (1992), Oron et al. (1994), and Traeger-Synodinos et al. (1996), thalassemia intermedia is caused by interaction between a triplicated alpha-globin locus (leading to alpha-globin overproduction) and beta-thalassemia heterozygosity. Traeger-Synodinos et al. (1996) reported 3 cases of beta-thalassemia heterozygosity with homozygous alpha-globin gene triplication and 17 beta-thalassemia heterozygotes with a single additional alpha-globin gene. Garewal et al. (1994) likewise reported 2 patients with a clinical presentation of thalassemia intermedia due to homozygosity for alpha-gene triplication and heterozygosity for an HBB gene mutation.

Landin et al. (1996) noted that 34 of 316 beta-globin variants due to single amino acid substitutions could be caused by more than 1 type of point mutation at the DNA level. They also noted that 3 beta-globin variants (Hb Edmonton, Hb Bristol, and Hb Beckman) and 1 alpha-globin variant (Hb J-Kurosh) could not be produced by a single nucleotide substitution; 2 substitutions were required.

Several hemoglobin variants were first detected in the course of study of glycated hemoglobin (HbA1c) in diabetics, e.g., 141900.0429 and 141900.0477. The alternative situation, diagnosis of diabetes during the performance of hemoglobin electrophoresis for study of anemia, was observed by Millar et al. (2002).

Sierakowska et al. (1996) found that treatment of mammalian cells stably expressing the IVS2-654 beta HBB gene (141900.0348) with antisense oligonucleotides targeted at the aberrant splice sites restored correct splicing in a dose-dependent fashion, generating correct human beta-globin mRNA and polypeptide. Both products persisted for up to 72 hours after treatment. The oligonucleotides modified splicing by a true antisense mechanism without overt unspecific effects on cells growth and splicing of other pre-mRNAs. This novel approach in which antisense oligonucleotides are used to restore rather than to downregulate the activity of the target gene is applicable to other splicing mutants and is of potential clinical interest.

Erythrocytosis

Huisman et al. (1996) listed (in their Table 6B) 38 HBB variants causing erythrocytosis, plus 20 others causing mild erythrocytosis and 1 causing erythrocytosis in combination with hemolysis. (Some authors, Boyer et al. (1972), Charache et al. (1975), and Brennan et al. (1982), use polycythemia rather than erythrocytosis as the designation for the compensatory increase in red blood cell mass that accompanies hemoglobins with increased oxygen affinity. The 2 terms must be considered synonymous. Some, e.g., Hamilton et al. (1969), use erythremia. Although also a synonym of polycythemia and erythrocytosis, erythremia has become essentially obsolete.)

Hereditary Persistence of Fetal Hemoglobin

Part of the mutational repertoire of the beta-globin locus is hereditary persistence of fetal hemoglobin (HPFH; 141749) due to deletion. Two types (types I and II) occur in blacks and have as their basis deletion of the delta and beta loci. An Italian type and an Indian type are likewise deletion forms of HPFH; see review by Saglio et al. (1986). In 2 Italian brothers with a G-gamma/A-gamma form of hereditary persistence of fetal hemoglobin, Camaschella et al. (1990) demonstrated a deletion starting 3.2 kb upstream from the delta gene and ending within the enhancer region 3-prime to the beta-globin gene. The deletion removed 1 of the 4 binding sites for an erythroid specific transcriptional factor (NF-E1). It appeared that the residual enhancer element, relocated near gamma genes, may increase fetal hemoglobin expression.

Delta-Beta Thalassemia

In the so-called Corfu form of delta-beta-thalassemia, Kulozik et al. (1988) found that a deletion removed 7,201 basepairs containing part of the delta-globin gene and sequences upstream. The beta-globin gene contained a G-to-A mutation at position 5 in IVS1. The gamma-globin gene promoters were normal. In transfected HeLa cells, a normal message was produced from the mutated beta-globin gene at a level of approximately 20% of the normal, the remaining 80% being spliced at cryptic sites in exon 1 and intron 1. This indicated that the mutation in the beta-globin gene is not the sole cause of the complete absence of hemoglobin A in this form of thalassemia. Kulozik et al. (1988) concluded that the 7.2-kb deletion contains sequences necessary for the normal activation of the beta-globin gene. In the homozygous state there is complete absence of hemoglobin A and hemoglobin A(2) and a high level of hemoglobin F. Traeger-Synodinos et al. (1991) gave further data on the Corfu mutation.

Protection Against Malaria

Gouagna et al. (2010) used cross-sectional surveys of 3,739 human subjects and transmission experiments involving 60 children and over 6,000 mosquitoes in Burkina Faso, West Africa, to test whether the HBB variants HbC (141900.0038) and HbS (141900.0243), which are protective against malaria, are associated with transmission of the parasite from the human host to the Anopheles mosquito vector. They found that HbC and HbS were associated with significant 2-fold in vivo (p = 1.0 x 10(-6)) and 4-fold ex vivo (p = 7.0 x 10(-5)) increases of parasite transmission from host to vector. Gouagna et al. (2010) concluded that human genetic variation at the HBB locus can influence the efficiency of malaria transmission, possibly by promoting sexual differentiation of P. falciparum as a downstream phenotypic event. Alternatively, Gouagna et al. (2010) suggested that the higher infectivity of individuals with HBB variants in their study could be due to less frequent use of antimalarial drugs. In a commentary, Pasvol (2010) noted that little is known regarding the mechanisms involved in switching from the parasite asexual stages to the induction of gametogenesis, but that the hemoglobinopathies may provide a scenario beneficial to both host and parasite.

Reviews

Kazazian and Boehm (1988) gave an update on the variety of beta-thalassemias. Large deletions are a rare cause of beta-thalassemia; as of early 1989, 63 single nucleotide substitutions or small deletions and 7 large deletions had been described as the basis of beta-thalassemia (Kazazian, 1989).

Huisman (1990) provided a list of over 110 different beta-thalassemia alleles, most of them of the nondeletional type.

Huisman (1992) edited an up-to-date listing of the deletions, mutations, and frameshifts leading to beta-thalassemia, which had been published 3 times previously, and added a new table on the delta-thalassemias, prepared by Erol Baysal. Kazazian et al. (1992) tabulated a total of 9 beta-globin mutations producing dominant thalassemia-like phenotypes. Widespread ethnic derivation was demonstrated.

Krawczak et al. (1992) reviewed the mutational spectrum of single basepair substitutions in mRNA splice junctions on the basis of 101 different examples of point mutations occurring in the vicinity of splice junctions and held to be responsible for human genetic disease. The data comprised 62 mutations at 5-prime splice sites, 26 at 3-prime splice sites, and 13 that resulted in the creation of novel splice sites such as HbE. They estimated that up to 15% of all point mutations causing human genetic disease result in an mRNA splicing defect.

Carver and Kutlar (1995) listed 323 beta-chain variants as of January 1995. This number did not include beta-chain variants with deletions and/or insertions or those with extended polypeptide chains. Baysal and Carver (1995) provided an update (eighth edition) of their catalog, or repository, of beta-thalassemia and delta-thalassemia.

Huisman et al. (1996) provided a syllabus of human hemoglobin variants listing the characteristics as well as precise molecular change of known beta-globin mutants; these numbered 335 single-base mutations and 17 variants with 2 amino acid replacements as of January 1996. They also included hemoglobin variants resulting from fusion of parts of the beta-chain and delta-chain, variants with elongated beta-chains at both the C-terminal and N-terminal ends, and variants with small deletions and/or insertions in the beta-chain. Not included were deletions and mutations that result in beta-thalassemia, even if such a change, point mutation, or frameshift occurred in one of the coding regions of the HBB gene. Information regarding these abnormalities were provided elsewhere, e.g., Baysal and Carver (1995).

Huisman et al. (1996) stated that 138 of the 146 codons of the HBB gene have been mutated; 5 mutations are known for 6 codons (22, 67, 97, 121, 143, and 146), 6 mutations for codon 92, and 7 mutations for codon 99. Most of the mutations have been deduced from the sequence of the amino acid sequence of the variant protein and the known sequence of the HBB gene; slightly more than 10% of the mutations have been determined through DNA sequencing. Occasionally discrepancy was observed, such as at position 50 and 67 of the beta-globin chain.

Database of Hemoglobin Variants

Hardison et al. (2002) constructed a web-accessible relational database of hemoglobin variants and thalassemia mutations called HbVar, in which old and new data are incorporated. Queries can be formulated based on fields in the database. For example, tables of common categories of variants, such as all variants involving the HBA1 gene (141800) or all those that result in high oxygen affinity, can be assembled. More precise queries are possible, such as 'all beta-globin variants associated with instability and found in Scottish populations.'

Locus Control Region Beta

Cases of gamma-delta-beta thalassemia are known in which the beta gene is intact but deletion 'in cis' occurs upstream, even at a distance, in a region designated LCRB. In a remarkable case reported by Curtin et al. (1985), a deletion extended from the third exon of the G-gamma gene upstream for about 100 kb. The A-gamma, pseudo-beta, delta, and beta genes in cis were intact. This malfunction of the beta-globin gene on a chromosome in which the deletion is located 25 kb away suggests that chromatin structure and conformation are important for globin gene expression. In experiments in which the human beta-globin locus was introduced into the mouse genome, Talbot et al. (1989) found a 6.5-kb control region which allowed achievement of endogenous levels of beta-globin expression. The control region included an erythroid cell-specific DNase I hypersensitive site (HS). Using pulsed field gel electrophoresis and PCR, Driscoll et al. (1989) found, in a case of gamma-delta-beta-thalassemia, a de novo deletion on a maternally inherited chromosome 11 involving about 30 kb of sequences 5-prime to the epsilon gene. The deletion extended from -9.5 kb to -39 kb 5-prime of epsilon and included 3 of the 4 DNase I hypersensitive sites (at -10.9 kb, -14.7 kb, and -18 kb 5-prime of epsilon). The remaining sequences of the beta-globin complex, including the DNase I hypersensitive sites at -6.1 kb and all structural genes in cis to the deletion, were physically intact. Again, a significance of the hypersensitive sites in regulating globin-gene expression was demonstrated.

Epsilon-gamma-delta-beta-thalassemias are all caused by deletions of the beta-globin gene cluster on 11p. At the molecular level, the deletions fall into 2 categories: group I removes all or a greater part of the beta-globin cluster, including the beta-globin gene; group II removes extensive upstream regions leaving the beta-globin gene itself intact despite which its expression is silenced because of inactivation of the upstream beta-locus control region. A group I deletion was reported by Curtin et al. (1985). A group I deletion was reported in a Chilean family by Game et al. (2003), and an upstream deletion (group II) was reported in a Dutch family by Harteveld et al. (2003). Rooks et al. (2005) described 3 novel epsilon-gamma-delta-beta-thalassemia deletions in 3 English families, referred to as English II, III, and IV to distinguish them from the family of Curtin et al. (1985), which was also English (I). Two of the deletions removed the entire beta-globin gene complex, including a variable number of flanking olfactory receptor genes.

The significance of the hypersensitive sites to globin gene expression had also been demonstrated by Grosveld et al. (1987) who achieved high levels of position-independent beta-gene expression in transgenic mice with a specially constructed beta-globin minilocus in which 5-prime and 3-prime hypersensitive sequences flanked a beta-globin gene. The hypersensitive sequences, termed locus-activating regions (LARs), are erythroid-tissue-specific and developmentally stable. Curtin et al. (1989) performed experiments similar to those of Grosveld et al. (1987) with like results. (A similar positive control region for the cluster of alpha-globin genes was deduced by Hatton et al. (1990) on the basis of deletion in a case of alpha-thalassemia; see 141800.) See 187550 for evidence of an unlinked remote regulator of HBB gene expression. Townes and Behringer (1990) reviewed the topic of the locus activating region. They presented a model for developmental control of human globin gene expression (see their Figure 2). With respect to the cap site of the human epsilon-globin gene, LAR site I is located at position -6.1 kb; site II, at -10.9 kb; site III, at -14.7 kb; and site IV, at -18 kb. Moon and Ley (1990) cloned murine DNA sequences homologous to the human LAR site II. These sequences are linked to the mouse beta-globin gene cluster in the same basic arrangement as the human beta-globin gene cluster. Furthermore, the 2 LARs share 70% identical sequence and several enhancer-type functions. LAR sequences are almost certainly not confined to the human beta-globin locus. The investigators stated that these sequences may be critical components of any gene family that comprises multiple members that are regulated differently during development.

Perichon et al. (1993) demonstrated interethnic polymorphism of 1 segment of the LCRB region in sickle cell anemia patients. Distinct polymorphic patterns of a simple sequence repeat were observed in strong linkage disequilibrium with each of the 5 major beta-S haplotypes.

Studies by Grosveld et al. (1987) and by Blom van Assendelft et al. (1989) established that 6 DNase I hypersensitive sites flank the globin genes. One HS site is located 20 kb downstream of the beta-globin cluster and 5 HS sites are located 6-22 kb upstream within the locus control region (LCR). Peterson et al. (1996) examined the effects of deletion of the LCR 5-prime HS3 element and the 5-prime HS2 element on globin gene expression by recombining a 2.3-kb deletion of 5-prime HS3 or a 1.9-kb deletion of 5-prime HS2 into a beta-globin locus YAC, which was then used to produce transgenic mice. When the LCR 5-prime HS3 element is deleted there is decreased expression of epsilon-globin in the yolk sac. Deletion of 5-prime HS2 resulted in a minor but statistically significant decrease in epsilon-, gamma-, and beta-globin expression. From these results Peterson et al. (1996) concluded that there is functional redundancy among the HS sites. The effects of the 5-prime HS3 deletion on epsilon-globin gene expression led them to conclude that specific interactions between the HSs and the globin genes underlie activation of globin genes during specific stages of development.

Epner et al. (1998) deleted the murine beta-globin LCR from its native chromosomal location. The approximately 25-kb deletion eliminated all sequences and structures homologous to those defined as the human LCR. In differentiated embryonic stem cells and erythroleukemia cells containing the LCR-deleted chromosome, DNase I sensitivity of the beta-globin domain was established and maintained, developmental regulation of the locus was intact, and beta-like globin RNA levels were reduced 5 to 25% of normal. Thus, in the native murine beta-globin locus, the LCR was necessary for normal levels of transcription, but other elements were sufficient to establish the open chromatin structure, transcription, and developmental specificity of the locus. These findings suggest a contributory rather than dominant function for the LCR in its native location.

Bauchwitz and Costantini (2000) quantified the effects of beta-globin sequence modifications on epsilon-, gamma-, and delta-globin levels in transgenic mice. Embryonic day 11.5 primitive erythroid cells showed a large increase in epsilon-globin in the absence of the beta-globin gene, which is weakly expressed at that stage of development. Embryonic day 17.5 fetal liver and adult erythroid cells, in which beta-globin expression approaches its maximum, showed only a small stimulation of gamma- and delta-globin levels in the absence of beta-globin sequence. Analysis of erythroid colonies produced by in vitro differentiation of embryonic stem cells indicated that the absence of the human beta-globin gene had no effect on gamma-globin expression. The authors concluded that competitive influences need not be linked directly to transcriptional level or distance from the LCR, and that the large increases in gamma-globin levels seen in some human deletional beta-thalassemias and hereditary persistence of fetal hemoglobin conditions are most likely due to effects other than loss of beta-globin competition. In transgenic mice with beta-globin sequences inserted between epsilon and the LCR in a beta-locus, the expression of epsilon-, gamma-, and delta-globins suggested that stage-specific sensitivity to loss of LCR activity may be a more important parameter than position relative to the LCR.

Alami et al. (2000) created a yeast artificial chromosome containing an unmodified human beta-globin locus, and introduced it into transgenic mice at various locations in the genome. The locus was not subject to detectable stable position effects but did undergo mild-to-severe variegating position effects at 3 of the 4 noncentromeric integration sites tested. The distance and the orientation of the LCR relative to the regulated gene contributed to the likelihood of variegating position effects, and affected the magnitude of its transcriptional enhancement. DNaseI hypersensitive site (HSS) formation varied with the proportion of expressing cells (variegation), rather than the level of gene expression, suggesting that silencing of the transgene may be associated with a lack of HSS formation in the LCR region. The authors concluded that transcriptional enhancement and variegating position effects are caused by fundamentally different but interdependent mechanisms.

Navas et al. (2002) generated transgenic mouse lines carrying a beta-globin locus YAC lacking the LCR to determine if the LCR is required for globin gene activation. Beta-globin gene expression was analyzed by RNase protection, but no detectable levels of epsilon-, gamma-, and beta-globin gene transcripts were produced at any stage of development. Lack of gamma-globin gene expression was also seen in a beta-YAC transgenic mouse carrying a gamma-globin promoter mutant that causes hereditary persistence of fetal hemoglobin (see 142200.0026) and an HS3 core deletion that specifically abolishes gamma-globin gene expression during definitive erythropoiesis. The authors concluded that the presence of the LCR is a minimum requirement for globin gene expression.

Navas et al. (2003) assessed the contribution of the GT6 motif within HS3 of the LCR on downstream globin gene expression by mutating GT6 in a beta-globin locus YAC and measuring the activity of beta-globin genes in GT6-mutated beta-YAC transgenic mice. They found reduced expression of epsilon- and gamma-globin genes during embryonic erythropoiesis. During definitive erythropoiesis, gamma-globin gene expression was significantly reduced while beta-globin gene expression was virtually indistinguishable from that of wildtype controls. Navas et al. (2003) concluded that the GT6 motif is required for normal epsilon- and gamma-globin gene expression during embryonic erythropoiesis and for gamma-globin gene expression during definitive erythropoiesis in the fetal liver.

Bottardi et al. (2005) noted that abnormal epigenetic regulation of gene expression contributes significantly to a variety of human pathologies including cancer. Deletion of HS2 at the human beta-globin locus control region can lead to abnormal epigenetic regulation of globin genes in transgenic mice. The authors used 2 HS2-deleted transgenic mouse lines as a model to demonstrate that heritable alteration of chromatin organization at the human beta-globin locus in multipotent hematopoietic progenitors can contribute to the abnormal expression of the beta-globin gene in mature erythroid cells. This alteration was characterized by specific patterns of histone covalent modifications that were inherited during erythropoiesis and, moreover, was plastic because it could be reverted by transient treatment with a histone deacetylase inhibitor. Bottardi et al. (2005) concluded that aberrant epigenetic regulation can be detected and modified before tissue-specific gene transcription.

Note Regarding the Allelic Variants Section

In the allelic variants listed below, as well as in the allelic variants listed under the other globin genes, the codon count begins with the first amino acid of the mature protein because a large portion of the variants were characterized on the basis of a protein rather than the gene itself. It is more customary for the count to begin with the methionine initiator codon as number one. Thus, the HbS mutation (141900.0243) is designated glu6-to-val; in the gene based system of counting now used, it would be designated glu7-to-val. Some inconsistency is represented by the fact that some initiator mutations in the globin genes are indicated by a system counting from the initiator methionine; e.g., beta-thalassemia due to met1-to-ile (141900.0430).


Animal Model

Ciavatta et al. (1995) created a mouse model of beta-zero-thalassemia by targeted deletion of both adult beta-like globin genes, beta(maj) and beta(min), in mouse embryonic stem cells. Heterozygous animals derived from the targeted cells were severely anemic with dramatically reduced hemoglobin levels, abnormal red cell morphology, splenomegaly, and markedly increased reticulocyte counts. Homozygous animals died in utero; however, heterozygous mice were fertile and transmitted the deleted allele to progeny. The anemic phenotype was completely rescued in progeny derived from mating beta-zero-thalassemic animals with transgenic mice expressing high levels of human hemoglobin A. The authors suggested that beta-zero-thalassemic mice could be used to test genetic therapy for beta-zero-thalassemia and could be bred with transgenic mice expressing high levels of hemoglobin S to produce an improved mouse model of sickle cell disease.

Hemoglobin disorders were among the first to be considered for gene therapy. Transcriptional silencing of genes transferred into hematopoietic stem cells, however, posed one of the most significant challenges to its success. If the transferred gene is not completely silenced, a progressive decline in gene expression as mice age often is encountered. These phenomena were observed to various degrees in mouse transplant experiments using retroviral vectors containing a human beta-globin gene, even when cis-linked to locus control region derivatives. Kalberer et al. (2000) investigated whether ex vivo preselection of retrovirally transduced stem cells on the basis of expression of the green fluorescent protein driven by the CpG island phosphoglycerate kinase (311800) promoter could ensure subsequent long-term expression of a cis-linked beta-globin gene in the erythroid lineage of transplanted mice. They observed that 100% of 7 mice engrafted with preselected cells concurrently expressed human beta-globin and green fluorescent protein in 20 to 95% of their red blood cells for up to 9.5 months posttransplantation, the longest time point assessed. This expression pattern was successfully transferred to secondary transplant recipients. In the presence of the beta-locus control region hypersensitivity site 2 alone, human beta-globin mRNA expression levels ranged from 0.15 to 20% with human beta-globin chains detected by HPLC. Neither the proportion of positive blood cells nor the average expression levels declined with time in translated recipients.

Persons and Nienhuis (2000) discussed the background of the work by Kalberer et al. (2000), including position effect variegation (PEV). Both PEV and silencing mechanisms may act on a transferred globin gene residing in chromatin outside of the normal globin locus during the important terminal phases of erythroblast development when globin transcripts normally accumulate rapidly despite heterochromatization and shutdown of the rest of the genome.


History

By autoradiography using heavy-labeled hemoglobin-specific messenger RNA, Price et al. (1972) found labeling of a chromosome 2 and a group B chromosome. They concluded, incorrectly as it turned out, that the beta-gamma-delta linkage group was on a group B chromosome since the zone of labeling was longer on that chromosome than on chromosome 2 (which by this reasoning was presumed to carry the alpha locus or loci). Study of a case of the Wolf-Hirschhorn syndrome (4p-) suggested that the B group chromosome involved is chromosome 4. Barbosa et al. (1975) excluded a recombination fraction of less than 0.30 for MN and Hb-beta.

McCurdy et al. (1975) thought the beta locus in some persons might be duplicated; they observed a black woman who had hemoglobin A and 2 different variant hemoglobins, each with a beta-globin change. One of these, however, proved to be a posttranslational change (Charache et al., 1977). El-Hazmi et al. (1986) suggested that the presence of 2 beta-globin genes might account for the finding of triple HpaI fragments in a case of sickle cell anemia. They explained its origin by unequal crossing-over.

Housman et al. (1979) used a panel of hybrid hamster-human cells deleted by x-ray and selected by a double antibody technique (the method of Kao, Jones, and Puck) to assign the NAG cluster to 11p12, between LDHA distally and ACP2 proximally. The orientation of the cluster in relation to the centromere was not known.

Although some workers have put the insulin (176730), beta-globin, and HRAS (190020) genes on 11p15, Chaganti et al. (1985) located these differently by in situ hybridization to meiotic chromosomes: INS, 11p14.1; HRAS, 11p14.1; HBB, 11p11.22; and PTH (not previously assigned), 11p11.21.


ALLELIC VARIANTS 541 Selected Examples):

.0001   HEMOGLOBIN AALBORG

HBB, GLY74ARG
SNP: rs33916541, gnomAD: rs33916541, ClinVar: RCV000016242

See Williamson et al. (1990).


.0002   HEMOGLOBIN ABRUZZO

HBB, HIS143ARG
SNP: rs33918338, gnomAD: rs33918338, ClinVar: RCV000016243, RCV001284490

See Tentori et al. (1972), Chiancone et al. (1974), and Zhao et al. (1990).


.0003   HEMOGLOBIN AGENOGI

HBB, GLU90LYS
SNP: rs33913712, ClinVar: RCV000016244, RCV000016877, RCV000756232, RCV001835627, RCV002222351

See Miyaji et al. (1966). As indicated by Corso et al. (1990), carriers of the mutation had been found in only 3 families, an American black, a Sicilian, and a Hungarian family, suggesting independent origins of the mutation. Corso et al. (1990) described another Sicilian family in which 5 members carried Hb Agenogi; in 1, it was associated with beta-zero-thalassemia. The proposita, a 40-year-old woman with 2 children, came to attention because of mild chronic anemia and biliary colic due to gallstones.

Noguera et al. (2002) described Hb Agenogi in an Argentinian patient with Syrian and Hungarian ancestry. The mutation had previously been described in only 5 families, one of which was from Hungary.


.0004   HEMOGLOBIN ALABAMA

HBB, GLN39LYS
SNP: rs11549407, gnomAD: rs11549407, ClinVar: RCV001811595, RCV002280786

See Brimhall et al. (1975).


.0005   HEMOGLOBIN ALAMO

HBB, ASN19ASP
SNP: rs34866629, ClinVar: RCV000016246

See Lam et al. (1977) and Arends et al. (1987).


.0006   HEMOGLOBIN ALBERTA

ERYTHROCYTOSIS 6, INCLUDED
HBB, GLU101GLY
SNP: rs33937393, ClinVar: RCV000016247, RCV000641405

See Mant et al. (1977), Stinson (1977), and Wong et al. (1978).


.0007   HEMOGLOBIN ALTDORF

HBB, ALA135PRO
SNP: rs35492035, ClinVar: RCV000016248

See Marti et al. (1976).


.0008   HEMOGLOBIN ANDREW-MINNEAPOLIS

ERYTHROCYTOSIS 6, INCLUDED
HBB, LYS144ASN
SNP: rs35020585, gnomAD: rs35020585, ClinVar: RCV000016249, RCV000144412, RCV000641406, RCV001811146

See Zak et al. (1974). Hebbel et al. (1978) used this hemoglobin to make ingenious observations on adaptation of humans to high altitudes.


.0009   HEMOGLOBIN ANKARA

HBB, ALA10ASP
SNP: rs33947457, ClinVar: RCV000016250

See Arcasoy et al. (1974) and Harano et al. (1981).


.0010   HEMOGLOBIN ARLINGTON PARK

HBB, GLU6LYS AND LYS95GLU
SNP: rs33914359, rs33930165, gnomAD: rs33914359, rs33930165, ClinVar: RCV000016251, RCV000016284, RCV000016285, RCV000016504, RCV000016505, RCV000016506, RCV000016507, RCV000016508, RCV000202507, RCV000224028, RCV000506157, RCV000576347, RCV000755549, RCV001535943, RCV001813746, RCV001835628, RCV002288494, RCV002415418, RCV003137529, RCV003150807, RCV003335041, RCV003398524

May have arisen either through a second mutation in a person with HbC or Hb N(Baltimore), or through crossing-over in a person who was heterozygous for both mutant hemoglobins. See Adams and Heller (1977).


.0011   HEMOGLOBIN ATHENS-GEORGIA

HEMOGLOBIN WACO
HBB, ARG40LYS
SNP: rs34831026, gnomAD: rs34831026, ClinVar: RCV000016252, RCV000756230, RCV002265556

See Brown et al. (1976) and Moo-Penn et al. (1977).


.0012   HEMOGLOBIN ATLANTA

HBB, LEU75PRO
SNP: rs33950542, ClinVar: RCV000016254, RCV000016255

Unstable hemoglobin. See Hubbard et al. (1975) and Brennan et al. (1983).


.0013   HEMOGLOBIN ATLANTA-COVENTRY

HBB, LEU75PRO AND LEU141DEL
SNP: rs33950542, ClinVar: RCV000016254, RCV000016255

Brennan et al. (1986) described a 25-year-old man with congenital hemolytic anemia who was found to have the mutation of Hb Atlanta (beta75 leu-to-pro) and that of Hb Coventry (beta141 leu deleted) in the same beta-globin chain along with a normal beta-globin chain and a beta-globin chain with only the Hb Atlanta mutation. They stated that this is the sixth known example of 2 changes in 1 beta chain. They postulated that the doubly abnormal beta-globin was a beta-delta globin originating by a Lepore-type-mechanism. Brennan et al. (1992) found on restudy that leu141 was in fact not deleted but replaced by a novel amino acid which they suggested was hydroxyleucine; they proposed that the change resulted from posttranslational oxidation of leu141 as a consequence of perturbation of the haem environment caused by the leu75-to-pro mutation. The finding was consistent with the report of George et al. (1992) who found no evidence of deletion of leu141 in genomic DNA. The heterozygous patients have 3 hemoglobins: HbA, Hb Atlanta, and Hb Atlanta-Coventry. The last 2 are the products of a single gene. A similar situation obtains with Hb Vicksburg (141900.0293), in which deletion of leu75 is not coded for in genomic DNA. Coleman et al. (1988) posited somatic mutation in that instance; however, a mechanism similar to that with Hb Atlanta-Coventry is possible.


.0014   HEMOGLOBIN AUSTIN

HBB, ARG40SER
SNP: rs33918778, ClinVar: RCV000016256

See Moo-Penn et al. (1977).


.0015   HEMOGLOBIN AVICENNA

HBB, ASP47ALA
SNP: rs33980484, ClinVar: RCV000016257

See Rahbar et al. (1979).


.0016   HEMOGLOBIN BARCELONA

ERYTHROCYTOSIS 6, INCLUDED
HBB, ASP94HIS
SNP: rs33959340, ClinVar: RCV000016258, RCV000641409

See Wajcman et al. (1982). This is a high oxygen affinity hemoglobin variant.


.0017   HEMOGLOBIN BAYLOR

HBB, LEU81ARG
SNP: rs33936967, ClinVar: RCV000016259

See Schneider et al. (1977).


.0018   HEMOGLOBIN BEIRUT

HBB, VAL126ALA
SNP: rs33925391, gnomAD: rs33925391, ClinVar: RCV000016260, RCV001284157, RCV001778654

See Strahler et al. (1983) and Blibech et al. (1986).


.0019   HEMOGLOBIN BELFAST

HBB, TRP15ARG
SNP: rs33946157, gnomAD: rs33946157, ClinVar: RCV000016261

See Kennedy et al. (1974).

Galanello et al. (2004) reported the sixth occurrence of Hb Belfast, a change of codon 15 of the HBB gene from TGG (trp) to AGG (arg) (trp15 to arg; W15R), in a large Italian family with 9 affected members. The oxygen affinity of the isolated variant was increased. The clinical phenotype was silent or very mild, the only clinical finding being an intermittent moderate jaundice.


.0020   HEMOGLOBIN BEOGRAD

HEMOGLOBIN D (CAMPERDOWN)
HBB, GLU121VAL
SNP: rs33987957, gnomAD: rs33987957, ClinVar: RCV000016264, RCV000016265

See Efremov et al. (1973), Wilkinson et al. (1975), and Ruvidic et al. (1975).

Akar et al. (1995) described a dual restriction enzyme digestion protocol for discriminating between Hb Beograd and Hb D (Los Angeles) (glu121 to gln) when they occur in the same population. Both of these variants migrate like HbS on cellulose acetate electrophoresis. Hb O (Arab) (glu121 to lys; 141900.0202) represents no problem because that variant migrates differently on cellulose acetate electrophoresis. Also, the glu121-to-ter mutation (141900.0314) represents no problem because it is associated with a thalassemia phenotype. Other codon 121 mutations are Hb D (Neath) (glu121 to-ala; 141900.0445) and Hb St. Francis (glu121 to gly; 141900.0412).


.0021   HEMOGLOBIN BETH ISRAEL

HBB, ASN102SER
SNP: rs33948057, ClinVar: RCV000016266

Like Hb Kansas, this variant was associated with clinically evident cyanosis due to very low oxygen affinity (Nagel et al., 1976). (The hemoglobins M are not the only anomalous hemoglobins associated with cyanosis.)


.0022   HEMOGLOBIN BETHESDA

ERYTHROCYTOSIS 6, INCLUDED
HBB, TYR145HIS
SNP: rs33949869, ClinVar: RCV000016267, RCV000641411, RCV001811147

See Hayashi et al. (1971), Adamson et al. (1972), Bunn et al. (1972), and Schmidt et al. (1976). See Hb Rainier.


.0023   HEMOGLOBIN BICETRE

HBB, HIS63PRO
SNP: rs33985544, ClinVar: RCV000016268

See Wajcman et al. (1976) and Miller et al. (1986).


.0024   HEMOGLOBIN BOLOGNA

HBB, LYS61MET
SNP: rs34974709, ClinVar: RCV000016269

See Marinucci et al. (1981).


.0025   HEMOGLOBIN BORAS

HBB, LEU88ARG
SNP: rs33940204, ClinVar: RCV000016262

See Hollender et al. (1969) and Bird et al. (1987).


.0026   HEMOGLOBIN BOUGARDIREY-MALI

HBB, GLY119VAL
SNP: rs33947020, gnomAD: rs33947020, ClinVar: RCV000016263

See Chen-Marotel et al. (1979).


.0027   HEMOGLOBIN BREST

HBB, GLN127LYS
SNP: rs33971634, gnomAD: rs33971634, ClinVar: RCV000016270

See Baudin-Chich et al. (1988).


.0028   HEMOGLOBIN BRIGHAM

ERYTHROCYTOSIS 6, INCLUDED
HBB, PRO100LEU
SNP: rs33965000, ClinVar: RCV000016271, RCV000641413

This variant is a cause of erythrocytosis. See Lokich et al. (1973).


.0029   HEMOGLOBIN BRISBANE

HEMOGLOBIN GREAT LAKES
ERYTHROCYTOSIS 6, INCLUDED
HBB, LEU68HIS
SNP: rs33972593, ClinVar: RCV000016272, RCV000016273, RCV000641416

See Brennan et al. (1981), Rahbar et al. (1981), and Williamson et al. (1983).


.0030   HEMOGLOBIN BRISTOL

HBB, VAL67MET-TO-ASP
SNP: rs36008922, ClinVar: RCV000016276, RCV000016801

See Steadman et al. (1970) and Ohba et al. (1985).

Rees et al. (1996) reinvestigated the patient who was the subject of the first description of idiopathic Heinz body anemia (140700) (Cathie, 1952) and who was subsequently shown to have hemoglobin Bristol. Using both DNA and protein analysis, they showed that the original characterization of hemoglobin Bristol as val67 to asp was incorrect, in that a silent posttranslational modification of met to asp was mistaken for the primary mutation, which is, in fact, val67 to met. They also restudied 2 subsequent patients reported as having hemoglobin Bristol following protein sequencing in whom the same confusion occurred. They were able to describe a novel posttranslational modification in which the variant methionine amino acid residue is converted to an aspartate, probably catalyzed by the neighboring heme group and oxygen. The study emphasized the importance of analyzing both protein and DNA to characterize fully hemoglobin variants. Identification of the lesion as val67 to asp was made by Steadman et al. (1970).

Although DNA codes for 20 primary amino acids, more than 140 different residues have been identified in proteins due to varied posttranslational modifications. Most are relatively simple reactions involving enzymatic modification of the site change of amino acids to enhance or determine the properties of the particular protein; these processes include acetylation, phosphorylation, hydroxylation, and glycation. There are also a number of posttranslational modifications of hemoglobin A, such as glycation and carbamoylation, but these are due mostly to nonspecific metabolic affects that alter the chemical environment of the hemoglobin, rather than direct results of the properties of the hemoglobin itself. Unstable hemoglobin variants are characterized by the reduced solubility of the hemoglobin tetramer in the red cell in peripheral blood. Most result from mutations of amino acids in key positions, for example, heme- or alpha-beta contact points. Mutations can also alter the structure of the molecule such that posttranslational changes can occur, either of the variant amino acid itself or of other residues exposed by changes in the conformation of the molecule. More rarely, so-called silent modifications occur, in which 1 primary amino acid is converted to another primary amino acid. This is what happened in the case of hemoglobin Bristol. The modification of beta-143 leu, such that it appears to be deleted on protein sequencing, in hemoglobin Atlanta-Coventry (141900.0013) is the result of posttranslational modification, possibly from leucine to hydroxyleucine, as a result of the primary mutation that effects the heme surface. The same apparent deletion of leu-149 is observed with Hb Christchurch (141900.0049) and with Hb Manukau (141900.0438), which is also a mutation of val67 (val67 to gly). There are 6 reported hemoglobin variants in which deamidation of an asparaginyl residue to an aspartate occurs as a silent posttranslational modification: these include hemoglobin Osler (141900.0211). The posttranslational change from methionine to aspartate was the first example to be described (Rees et al., 1996); the exact mechanism of the change is not clear.


.0031   HEMOGLOBIN BRITISH COLUMBIA

ERYTHROCYTOSIS 6, INCLUDED
HBB, GLU101LYS
SNP: rs33966487, ClinVar: RCV000016274, RCV000641420

See Jones et al. (1977) and Stinson (1984).


.0032   HEMOGLOBIN BROCKTON

HBB, ALA138PRO
SNP: rs33919821, ClinVar: RCV000016275

See Moo-Penn et al. (1980, 1988) and Ulukutlu et al. (1989). Negri Arjona et al. (1992) found a GCT (ala)-to-CCT (pro) mutation in codon 138 in a 6-year-old Spanish girl with chronic hemolytic anemia requiring transfusion. The patient showed Heinz bodies. Her parents and a brother were normal, indicating that her disorder represented a new mutation.

Tsoi et al. (1998) identified Hb Brockton in a 9-year-old Chinese boy with long-standing hemolysis. As in previous reports, the mutation occurred de novo. Tsoi et al. (1998) noted that the patient also had moyamoya disease (see 252350).


.0033   HEMOGLOBIN BRUXELLES

HEINZ BODY HEMOLYTIC ANEMIA
HBB, PHE41DEL OR PHE42DEL
SNP: rs41417446, ClinVar: RCV000016277, RCV000016278, RCV001800300

Blouquit et al. (1989) demonstrated that hemoglobin Bruxelles, a beta-globin variant associated with severe congenital Heinz body anemia, has a deletion of 1 of the 2 adjacent phenylalanines, either phe41 or phe42. Other deletions affecting the phe41 or phe42 have been described. The nucleotide sequence of normal beta-globin mRNA is highly repetitive in the region of codons 41 to 46. Blouquit et al. (1989) suggested that the mutation originated through a frameshift mechanism.


.0034   HEMOGLOBIN BRYN MAWR

HEMOGLOBIN BUENOS AIRES
HBB, PHE85SER
SNP: rs35693898, ClinVar: RCV000016279, RCV003114195

See Bradley et al. (1972), Lehmann (1973), and Weinstein et al. (1973).


.0035   HEMOGLOBIN BUNBURY

HBB, ASP94ASN
SNP: rs33959340, ClinVar: RCV000016281, RCV000985741, RCV001804736

See Como et al. (1983). This is a high oxygen affinity hemoglobin variant.


.0036   HEMOGLOBIN BURKE

HBB, GLY107ARG
SNP: rs35017910, ClinVar: RCV000016282

See Turner et al. (1976) and Kobayashi et al. (1986).


.0037   HEMOGLOBIN BUSHWICK

HBB, GLY74VAL
SNP: rs33976006, ClinVar: RCV000016283

See Rieder et al. (1974), Ohba et al. (1985), and Efremov et al. (1987).


.0038   HEMOGLOBIN C

MALARIA, RESISTANCE TO, INCLUDED
HBB, GLU6LYS
SNP: rs33930165, gnomAD: rs33930165, ClinVar: RCV000016251, RCV000016284, RCV000016285, RCV000202507, RCV000224028, RCV000576347, RCV001535943, RCV001813746, RCV002288494, RCV002415418, RCV003137529, RCV003150807, RCV003335041, RCV003398524

See Itano and Neel (1950), Neel et al. (1953), Ranney et al. (1953), Hunt and Ingram (1959), Smith and Krevans (1959), Baglioni and Ingram (1961), River et al. (1961), and Fabry et al. (1981).

By restriction haplotyping, Boehm et al. (1985) concluded that the beta-C-globin gene in blacks had a single origin followed by spread of the mutation to other haplotypes through meiotic recombination 5-prime to the beta-globin gene. On 22 of 25 chromosomes studied, they found the same haplotype (defined by 8 polymorphic restriction sites), a haplotype seen only rarely among beta-A-bearing chromosomes. The 3 exceptions showed identity to the typical beta-C allele in the 3-prime end of the beta-globin gene cluster. Trabuchet et al. (1991) presented haplotyping information suggesting a unicentric origin of the HbC mutation in sub-Saharan Africa.

Rapid detection of the sickle cell mutation is possible by amplifying the region of codon 6 by PCR and digesting the amplification product by a restriction endonuclease whose recognition site is abolished by the A-to-T mutation, the resulting abnormal fragment being detected with ethidium bromide staining after electrophoresis. Detection of the HbC mutation is more difficult since no known restriction-endonuclease site is abolished or created by the mutation. Fischel-Ghodsian et al. (1990) described a rapid allele-specific PCR amplification technique that allowed detection of the HbC mutation in an even shorter time span than the one required for detecting the HbS mutation (141900.0243).

To test the hypothesis that hemoglobin C protects against severe malaria (611162), Agarwal et al. (2000) conducted a study in the predominantly Dogon population of Bandiagara, Mali, in West Africa, where the frequency of HbC is high (0.087) and that of HbS is low (0.016). They found evidence for an association between HbC and protection against severe malaria in the Dogon population. Indeed, the data suggested less selection for the HbAS state in this group than for HbAC.

In many children with sickle cell disease (603903), functional asplenia develops during the first year of life and septicemia is the leading cause of death in childhood. The risk of septicemia in sickle cell anemia is greatest during the first 3 years of life and is reduced markedly by prophylactic penicillin therapy. Less is known about splenic dysfunction and the risk of overwhelming sepsis in children with SC disease, although functional asplenia has been documented by radionuclide liver-spleen scans in some adult patients (Ballas et al., 1982) and an elevated erythrocyte pit count, a finding that indicates functional asplenia in children with sickle cell anemia, also has been found in some children with SC disease (Pearson et al., 1985). Lane et al. (1994) reported 7 fatal cases of pneumococcal septicemia in children with SC disease. The earliest death occurred in a 1-year-old child who had cyanotic congenital heart; the other children were aged 3.5 to 15 years. Only 1 child had received pneumococcal vaccine or prophylactic penicillin therapy. All 7 children had an acute febrile illness and rapid deterioration despite parenterally administered antibiotic therapy and intensive medical support. Erythrocyte pit counts in 2 patients were 40.3 and 41.7%, respectively (normal, less than 3.6%). Autopsy findings in 5 cases included splenic congestion without infarction in 5, splenomegaly in 4, and bilateral adrenal hemorrhage in 3. Lane et al. (1994) concluded that pneumococcal vaccine should be administered in all children with SC disease. The routine use of prophylactic penicillin therapy in infants and children with SC disease remained controversial. The mutation in codon 6 of HBB in HbS is GAG (glu) to GTG (val); the mutation in HbC is GAG (glu) to AAG (lys). See also 141900.0039 and 141900.0040.

Modiano et al. (2001) performed a large case-control study in Burkina Faso on 4,348 Mossi subjects, and demonstrated that hemoglobin C is associated with a 29% reduction in risk of clinical malaria in HbAC heterozygotes (P = 0.0008) and of 93% in HbCC homozygotes (P = 0.0011). These findings, together with the limited pathology of HbAC and HbCC compared to the severely disadvantaged HbSS and HbSC genotypes and the low HbS gene frequency in the geographic epicenter of HbC, support the hypothesis that, in the long-term and in the absence of malarial control, HbC would replace HbS in central West Africa.

Rihet et al. (2004) surveyed 256 individuals (71 parents and 185 sibs) from 53 families in Burkina Faso over 2 years and found that hemoglobin C carriers were found to have less frequent malaria attacks than AA individuals within the same age group (P = 0.01). Analysis of individual hemoglobin alleles yielded a negative association between HbC and malaria attack (P = 0.00013). Analyses that took into account confounding factors confirmed the negative association of HbC with malaria attack (P = 0.0074) and evidenced a negative correlation between HbC and parasitemia (P = 0.0009).

Fairhurst et al. (2005) reported a marked effect of hemoglobin C on the cell-surface properties of P. falciparum-infected erythrocytes involved in pathogenesis. Relative to parasite-infected normal erythrocytes (HbAA), parasitized AC and CC erythrocytes showed reduced adhesion to endothelial monolayers expressing CD36 (173510) and intercellular adhesion molecule-1 (ICAM1; 147840). They also showed impaired rosetting interactions with nonparasitized erythrocytes, and reduced agglutination in the presence of pooled sera from malaria-immune adults. Abnormal cell-surface display of the main variable cytoadherence ligand, PfEMP-1 (P. falciparum erythrocyte membrane protein-1), correlated with these findings. The abnormalities in PfEMP-1 display were associated with markers of erythrocyte senescence, and were greater in CC than in AC erythrocytes. Fairhurst et al. (2005) suggested that hemoglobin C might protect against malaria by reducing PfEMP1-mediated adherence of parasitized erythrocytes, thereby mitigating the effects of their sequestration in the microvasculature.

Recombinational hotspots are a ubiquitous feature of the human genome, occurring every 60 to 200 kb, and likely contribute to the observed pattern of large haplotypic blocks punctuated by low linkage disequilibrium (LD) over very short (1 to 2 kb) distances. Recombination breaks up ancestral LD and produces new combinations of alleles on which natural selection can act. Positive selection increases the frequency of beneficial mutations, creating LD via genetic 'hitchhiking.' The beta-globin hotspot spans approximately 1 kb and is located approximately 500 bp from the selected site at the beta-globin gene. The close proximity of these beta-globin regions allowed Wood et al. (2005) to empirically examine the signature of selection across a region that recombines at a rate 50 to 90 times higher than the genomic average of 1.1 cM/Mb. Early studies of the HbC polymorphism suggested that this allele was, like the hemoglobin S allele (141900.0243), also subject to balancing selection (Allison, 1954). Subsequently, it was shown that HbC provides protection against Plasmodium falciparum without significantly reducing fitness, indicating that this allele is increasing in frequency as a result of positive directional selection (Agarwal et al., 2000; Modiano et al., 2001; Hedrick, 2004; Rihet et al., 2004). Because the African HbC allele rarely exceeds frequencies of 20% and is geographically concentrated in central West Africa, it is thought that this mutation is very young. Wood et al. (2005) examined the extent of LD surrounding the African HbC allele to estimate its age and the strength of selection acting on this mutation and tested the hypothesis that the beta-globin recombinational hotspot decouples the selected HbC allele from nearby upstream regions. They estimated that the HbC mutation originated less than 5,000 years ago and that selection coefficients are between 0.04 and 0.09. Despite strong selection and the recent origin of the HbC allele, recombination (crossing-over or gene conversion) is observed within 1 kb 5-prime of the selected site on more than one-third of the Hb chromosomes sampled. The rapid decay in LD upstream of the HbC allele demonstrates the large effect the beta-globin hotspot has in mitigating the effects of positive selection on linked variation, in other words a reduction in 'hitchhiking.'

Modiano et al. (2008) adopted 2 partially independent haplotypic approaches to study the Mossi population in Burkina Faso, where both the HbS and HbC alleles are common. They showed that both alleles are monophyletic, but that the HbC allele has acquired higher recombinatorial and DNA slippage haplotypic variability or linkage disequilibrium decay and is likely older than HbS. Modiano et al. (2008) inferred that the HbC allele has accumulated mainly through recessive rather than a semidominant mechanism of selection.

Gouagna et al. (2010) used cross-sectional surveys of 3,739 human subjects and transmission experiments involving 60 children and over 6,000 mosquitoes in Burkina Faso, West Africa, to test whether the HBB variants HbC and HbS, which are protective against malaria, are associated with transmission of the parasite from the human host to the Anopheles mosquito vector. They found that HbC and HbS were associated with significant 2-fold in vivo (P = 1.0 x 10(-6)) and 4-fold ex vivo (P = 7.0 x 10(-5)) increases of parasite transmission from host to vector. In addition, the HbC allele was consistently associated with higher gametocyte rate.

Cyrklaff et al. (2011) found that HbS (141900.0243) and HbC affect the trafficking system that directs parasite-encoded proteins to the surface of infected erythrocytes. Cryoelectron tomography revealed that P. falciparum generates a host-derived actin cytoskeleton within the cytoplasm of wildtype red blood cells that connects the Maurer clefts with the host cell membrane and to which transport vesicles are attached. The actin cytoskeleton and the Maurer clefts were aberrant in erythrocytes containing HbS or HbC. Hemoglobin oxidation products, enriched in HbS and HbC erythrocytes, inhibited actin polymerization in vitro and may account for the protective role in malaria.


.0039   HEMOGLOBIN C (GEORGETOWN)

HEMOGLOBIN C (HARLEM)
HBB, GLU6VAL AND ASP73ASN
SNP: rs334, rs33945705, gnomAD: rs334, rs33945705, ClinVar: RCV000016286, RCV000016449, RCV000016573, RCV000016574, RCV000016575, RCV000016576, RCV000016577, RCV000016579, RCV000016580, RCV000016877, RCV000016879, RCV000030905, RCV000224000, RCV000477892, RCV000576548, RCV000587238, RCV000623118, RCV000723337, RCV000855647, RCV001192494, RCV001255121, RCV001535873, RCV001824571, RCV001826465, RCV002251908, RCV002288496, RCV003150808, RCV003407340

Red cells containing this hemoglobin, with 2 mutations in the HBB gene, sickle. The sickling is the result, of course, of the glu-to-val mutation, which is not counteracted by the asp73-to-asn mutation. It is called HbC (not S) because of its electrophoretic properties. See Pierce et al. (1963), Bookchin et al. (1966, 1968, 1970), and Lang et al. (1972).


.0040   HEMOGLOBIN C (ZIGUINCHOR)

HEMOGLOBIN ZIGUINCHOR
HBB, GLU6VAL AND PRO58ARG
SNP: rs334, rs33991472, gnomAD: rs334, ClinVar: RCV000016286, RCV000016573, RCV000016574, RCV000016575, RCV000016576, RCV000016577, RCV000016579, RCV000016580, RCV000016651, RCV000016877, RCV000016879, RCV000030905, RCV000224000, RCV000477892, RCV000576548, RCV000623118, RCV000723337, RCV001192494, RCV001255121, RCV001535873, RCV001824571, RCV002222352, RCV002251908, RCV002288496, RCV003150808, RCV003407340

As in the other cases of doubly substituted beta chains, either double mutation or intracistronic recombination in a genetic compound would explain the observation. This hemoglobin sickles because of its glu6-to-val substitution, but is called HbC (not S) because of its electrophoretic properties, which are those of classic HbC. See Goossens et al. (1975) and Hassan et al. (1977).


.0041   HEMOGLOBIN CAMDEN

HEMOGLOBIN MOTOWN
HEMOGLOBIN TOKUCHI
HBB, GLN131GLU
SNP: rs33910209, ClinVar: RCV000507699, RCV001281709, RCV002280781, RCV002280782, RCV002280783

See Wade Cohen et al. (1973) and Honig et al. (1980). Hmoglobin Motown was formerly thought to be a change at beta 127 (Gibb, 1981). See Ohba et al. (1975); hemoglobin Tokuchi was formerly thought to be a substitution of tyrosine for histidine at beta 2 (Shibata et al., 1963).


.0042   HEMOGLOBIN CAMPERDOWN

HBB, ARG104SER
SNP: rs33914944, gnomAD: rs33914944, ClinVar: RCV000016293, RCV000016780

See Wilkinson et al. (1975) and Zhao et al. (1990).


.0043   HEMOGLOBIN CARIBBEAN

HBB, LEU91ARG
SNP: rs33917785, ClinVar: RCV000016294, RCV001283991

See Ahern et al. (1976) and Ali et al. (1988).


.0044   HEMOGLOBIN CASTILLA

HBB, LEU32ARG
SNP: rs33948578, ClinVar: RCV000016295

See Garel et al. (1975).

Walker et al. (2003) described heterozygosity for Hb Castilla in an 8-month-old boy with persistent hemolytic anemia.


.0045   HEMOGLOBIN CHANDIGARH

HBB, ASP94GLY
SNP: rs34579351, ClinVar: RCV000016296

Dash et al. (1989) described Hb Chandigarh in a 35-year-old carrier of beta-thalassemia who was the father of a child diagnosed to have homozygous beta-thalassemia. At that time, the patient was normocytic with normal values of hemoglobin, PCV, and RBC count. Two other hemoglobin variants with substitutions at asp94 had been described: Hb Barcelona (asp94 to his; 141900.0016) and Hb Bunbury (asp94 to asn; 141900.0035), both of which were described as high oxygen affinity Hb variants, with or without erythrocytosis. Dash and Das (2004) reported on the same patient observed 15 years later. He then had marked hepatosplenomegaly and was found to have polycythemia. The asp94 residue was known to form a salt bridge between its carboxyl group and the imidazolium ion of the histidine residue at the C terminus. The loss of this salt bridge appears to destabilize the deoxy structure and shift the equilibrium from the deoxy to the oxy configuration.


.0046   HEMOGLOBIN CHEMILLY

ERYTHROCYTOSIS 6, INCLUDED
HBB, ASP99VAL
SNP: rs33971048, ClinVar: RCV000016297, RCV000641428

See Rochette et al. (1984).


.0047   HEMOGLOBIN CHEVERLY

HBB, PHE45SER
SNP: rs33978338, ClinVar: RCV000016298, RCV000757360, RCV003155027

See Yeager et al. (1983). (Hb Hammersmith is beta-42 phe to ser. Despite the functional and structural similarities, the clinical manifestations of Hb Cheverly are much milder than those of Hb Hammersmith.)


.0048   HEMOGLOBIN CHICO

HBB, LYS66THR
SNP: rs35939489, ClinVar: RCV000016299, RCV001811148

See Shih et al. (1987). Hb Chico has diminished oxygen affinity (Bonaventura et al., 1991). Its oxygen-binding constant is about half that of normal. Bonaventura et al. (1991) presented data on the molecular basis of this altered property.


.0049   HEMOGLOBIN CHRISTCHURCH

HBB, PHE71SER
SNP: rs34362537, ClinVar: RCV000016300

See Carrell (1970).


.0050   HEMOGLOBIN CITY OF HOPE

HBB, GLY69SER
SNP: rs33947415, gnomAD: rs33947415, ClinVar: RCV000016301, RCV000396079, RCV000587680, RCV000709890, RCV000855646, RCV001004567, RCV001107022, RCV001107023, RCV001535933

See Rahbar et al. (1984) and Kutlar et al. (1989). De Angioletti et al. (1992) detected Hb City of Hope by reversed phase high performance liquid chromatography in an asymptomatic carrier in Naples. The gly69-to-ser substitution, identified by fast atom bombardment mass spectrometry, was shown to be due to a TGG-to-TGA substitution by DNA sequencing. The mutation was associated with RFLP haplotype 9, instead of haplotype 1, as previously reported.


.0051   HEMOGLOBIN COCHIN-PORT ROYAL

HBB, HIS146ARG
SNP: rs33954264, ClinVar: RCV000016302

See Wajcman et al. (1975).

De Angioletti et al. (2002) described the comparable mutation in the delta chain of hemoglobin A, designated HBA2-Monreale (142000.0038).


.0052   HEMOGLOBIN COCODY

HBB, ASP21ASN
SNP: rs33950093, ClinVar: RCV000016303

See Boissel et al. (1981), Fabritius et al. (1985), and Ohba et al. (1990).


.0053   HEMOGLOBIN COLLINGWOOD

HBB, VAL60ALA
SNP: rs33931779, ClinVar: RCV000016304

See Williamson et al. (1983).


.0054   HEMOGLOBIN CONNECTICUT

HBB, ASP21GLY
SNP: rs33977536, ClinVar: RCV000016305

See Moo-Penn (1981).


.0055   HEMOGLOBIN COVENTRY

HBB, LEU141DEL
SNP: rs33935780, ClinVar: RCV000016306

The proband was a child who appeared to have 3 different beta chains in addition to the delta chain of HbA2 and the gamma chain of HbF (Casey et al. (1976, 1978)). The child had Hb Sydney (beta 67 val-to-ala) and deletion of beta 141 leu. These were in different beta genes. The presence of 3 beta genes suggested to Lehmann (1978) that the beta Coventry chain is in fact a beta-delta fusion chain. Fay et al. (1993) offered the explanation of posttranslational modification of leu-141, probably a conversion to hydroxyleucine, which was not detected by standard amino acid analysis and sequencing methods. Of interest was the finding that not only Hb Sydney but also another substitution at the same codon, val67-to-gly in Hb Manukau, showed this feature. Hemoglobin Coventry was also found in association with Hb Atlanta (leu75-to-pro) (141900.0012).


.0056   HEMOGLOBIN COWTOWN

ERYTHROCYTOSIS 6, INCLUDED
HBB, HIS146LEU
SNP: rs33954264, ClinVar: RCV000016307, RCV000641431

This variant was named for Fort Worth, Texas. Polycythemia is produced. One member of the family was treated with P32 for presumed polycythemia rubra vera (Schneider, 1978; Schneider et al., 1979). This and about 40 other hemoglobin variants are associated with erythrocytes. See Perutz et al. (1984).


.0057   HEMOGLOBIN CRANSTON

HBB, 2-BP INS, CODON 144
SNP: rs35660883, ClinVar: RCV000016308

This hemoglobin was found in an asymptomatic woman with a compensated hemolytic state due to an unstable hemoglobin variant (Bunn et al., 1975). The hemoglobin had an abnormally long beta chain that, starting at amino acid 144, had the following sequence: lys-ser-ile-thr-lys-leu-ala-phe-leu-leu-ser-asn-phe-tyr-COOH. This is the first HbA variant known to contain isoleucine. Bunn et al. (1975) concluded that Hb Cranston probably arose by nonhomologous crossing-over between 2 normal beta chain genes, resulting in the insertion of 2 nucleotides (AG) at position 144, to produce a frame shift. Hb Wayne is thought to be a frame shift mutation involving the alpha chain. Hb Tak is another hemoglobin with abnormally long beta chain. Hb Constant Spring, Hb Koya Dora, and Hb Icaria are hemoglobins with abnormally long alpha chains. See Shaeffer et al. (1980).


.0058   HEMOGLOBIN CRETE

HBB, ALA129PRO
SNP: rs34139813, rs35939430, gnomAD: rs34139813, rs35939430, ClinVar: RCV000016309, RCV001823097

See Maniatis et al. (1979).

Christopoulou et al. (2004) identified a 1368G-C transversion in exon 3 of the beta-globin gene, resulting in an ala129-to-pro (A129P) substitution. Both the proband and her mother, who were found to be heterozygous for Hb Crete, presented with mild microcytic anemia and normal hemoglobin A2 levels and iron metabolism indices.


.0059   HEMOGLOBIN CRETEIL

ERYTHROCYTOSIS 6, INCLUDED
HBB, SER89ASN
SNP: rs33917628, ClinVar: RCV000016310, RCV000641434, RCV001374642

Erythrocytosis results. See Thillet et al. (1976) and Poyart et al. (1978).


.0060   HEMOGLOBIN D (BUSHMAN)

HBB, GLY16ARG
SNP: rs63751285, gnomAD: rs63751285, ClinVar: RCV000016311

See Wade et al. (1967).


.0061   HEMOGLOBIN D (GRANADA)

HBB, GLU22VAL
SNP: rs33936254, gnomAD: rs33936254, ClinVar: RCV000016312, RCV000759803, RCV002490376

See de Pablos et al. (1987).


.0062   HEMOGLOBIN D (IBADAN)

HBB, THR87LYS
SNP: rs33993568, gnomAD: rs33993568, ClinVar: RCV000016313, RCV000506646, RCV001826463

See Watson-Williams et al. (1965).


.0063   HEMOGLOBIN D (IRAN)

HBB, GLU22GLN
SNP: rs33959855, gnomAD: rs33959855, ClinVar: RCV000016314, RCV000589411, RCV001280542

See Rohe et al. (1972), Rahbar (1973), and Serjeant et al. (1982).


.0064   HEMOGLOBIN D (OULED RABAH)

HBB, ASN19LYS
SNP: rs63750840, gnomAD: rs63750840, ClinVar: RCV000016321, RCV001811149

See Elion et al. (1973) and Ren et al. (1988).

Among 598 children from the Berber population of the Mzab, Merghoub et al. (1997) found HbC and Hb D (Ouled Rabah) in the same gene frequency (0.015). Hb D(Ouled Rabah) is considered a private marker of the Kel Kummer Tuaregs. Haplotype analysis suggested a single origin of the Hb D mutation. Genetic markers calculated from blood group data clustered Mozabites and Tuaregs with the other Berber-speaking groups, Arabic-speaking populations being more distant. However, they found no specific relationship between the Mozabites and Kel Kummers. Tuaregs in general exhibit features that tend to differentiate them from other Berber-speaking groups. Merghoub et al. (1997) concluded that Hb D(Ouled Rabah) may be specific for Berber-speaking populations. Merghoub et al. (1997) noted that the origin of the Berber people is not clearly established. North Africa was peopled around the sixteenth millennium B.C.; transition to agriculture occurred around 9500 to 7000 B.C., spreading from the Near East to Egypt. The Arab invasion in the seventh and eighth centuries brought Islamization and dispersal of the Berber culture. Present-day populations of North Africa are mostly Arabic-speaking, whatever their remote origin. Berbers, however, with their languages and customs, still live in small niches of northern Morocco and Algeria, and in some northern oases of the Sahara, including those of the Mzab (Algeria). The Tuaregs also speak Berber languages. They inhabit the south of the Sahara and have been involved for centuries in trans-Saharan trade. Tuaregs have their own culture that probably diverged from the Berber world through isolation.


.0065   HEMOGLOBIN D (PUNJAB)

HEMOGLOBIN D (CHICAGO)
HEMOGLOBIN D (LOS ANGELES)
HEMOGLOBIN D (NORTH CAROLINA)
HEMOGLOBIN D (PORTUGAL)
HEMOGLOBIN OAK RIDGE
HBB, GLU121GLN
SNP: rs33946267, gnomAD: rs33946267, ClinVar: RCV000016317, RCV000016617, RCV000016758, RCV000016858, RCV000029994, RCV000202465, RCV000723826, RCV000778329, RCV001175348, RCV002247348

See Benzer et al. (1958), Bowman and Ingram (1961), Stout et al. (1964), Schneider et al. (1968), Lehmann and Carrell (1969), Ozsoylu (1970), Imamura and Riggs (1972), Bunn et al. (1978), Trent et al. (1984), Worthington and Lehmann (1985), Husquinet et al. (1986), and Harano et al. (1987). Hemoglobin D (Punjab) is common worldwide. It is the most frequent abnormal hemoglobin in Xinjiang Uygur Autonomous Region of China (Li et al., 1986). Zeng et al. (1989) used the PCR method for population studies of this variant. Using PCR and direct sequencing, Schnee et al. (1990) demonstrated the predicted G-to-C substitution in codon 121.


.0066   HEMOGLOBIN DEER LODGE

HBB, HIS2ARG
SNP: rs33983205, gnomAD: rs33983205, ClinVar: RCV000016324, RCV001811150

See Labossiere et al. (1972), Powars et al. (1977), and Shulman and Bunn (1988).


.0067   HEMOGLOBIN DETROIT

HBB, LYS95ASN
SNP: rs36038739, ClinVar: RCV000016325, RCV003476893

See Moo-Penn et al. (1978).


.0068   HEMOGLOBIN DJELFA

HBB, VAL98ALA
SNP: rs33985510, ClinVar: RCV000016326

See Gacon et al. (1977).


.0069   HEMOGLOBIN DOHA

HBB, NH2 EXTENSION, VAL1GLU
SNP: rs33949930, gnomAD: rs33949930, ClinVar: RCV000016327

Kamel et al. (1985) investigated a Qatari family with an electrophoretically fast-moving hemoglobin that they found contained an abnormal beta chain with the sequence met-glu-his-leu at the NH2-end. Substitution of glutamic acid for valine at beta 1 apparently prevented removal of the initiator methionine. The methionine was blocked by a molecule not completely identified. No clinical consequences were observed in heterozygotes.

This variant was numbered based on the first amino acid of the mature protein. In the gene-based system of counting, this variant is VAL2GLU.


.0070   HEMOGLOBIN DUARTE

HBB, ALA62PRO
SNP: rs34933455, ClinVar: RCV000016328

See Beutler et al. (1974).


.0071   HEMOGLOBIN E

BETA-PLUS-THALASSEMIA
BETA-E-THALASSEMIA
MALARIA, RESISTANCE TO, INCLUDED
HBB, GLU26LYS
SNP: rs33950507, gnomAD: rs33950507, ClinVar: RCV000016329, RCV000016330, RCV000016331, RCV000016332, RCV000016617, RCV000202534, RCV000496072, RCV000506024, RCV000521111, RCV000778330, RCV000853358, RCV001536065, RCV002288495, RCV002415419, RCV003415712

This mutation is a cause of beta-plus-thalassemia (613985). See Hunt and Ingram (1961), Shibata et al. (1962), Blackwell et al. (1970), Fairbanks et al. (1980), Benz et al. (1981), and Kazazian et al. (1984).

Orkin et al. (1982) reported the complete nucleotide sequence of a beta-E-globin gene. They found a GAG-to-AAG change in codon 26 as the only abnormality. Expression of the beta-E gene was tested by introducing it into HeLa cells. Two abnormalities of RNA processing were shown: slow excision of intervening sequence-1 and alternative splicing into exon 1 at a cryptic donor sequence within which the codon 26 nucleotide substitution resides.

Antonarakis et al. (1982) used the Kazazian haplotype approach of analyzing DNA polymorphisms in the beta-globin cluster to present evidence that the beta-E mutation occurred at least twice in Southeast Asia. Thein et al. (1987) demonstrated that the GAG-to-AAG change could be recognized by the restriction enzyme MnlI which cleaves DNA at the sequence 3-prime-GGAG-5-prime.

Rey et al. (1991) described SE disease in 3 black American children of Haitian origin. They pointed out that the disorder is probably more benign than SC disease, SO(Arab) disease, and SC(Harlem) disease, all of which have increased risk of the complications of sickling including pneumococcal sepsis.

Rees et al. (1996) reported a girl homozygous for Hb E with severe anemia and anisopoikilocytosis, who was also homozygous for pyrimidine 5-prime nucleotidase deficiency (P5N; 266120). In erythrocytes deficient for P5N, the stability of the Hb E was decreased.

Hemoglobin E is very common in parts of Southeast Asia. Chotivanich et al. (2002) examined the possible protective role of Hb E and other prevalent inherited hemoglobin abnormalities against malaria (611162) in Thailand. They assessed the effect of Hb E by means of a mixed erythrocyte invasion assay. In vitro, starting at 1% parasitemia, Plasmodium falciparum preferentially invaded normal (HbAA) compared to abnormal hemoglobin red blood cells, including those heterozygous and homozygous for Hb E. The heterozygote HbAE cells differed markedly from all the other cells tested, with invasion restricted to approximately 25% of the red blood cells. Despite their microcytosis, AE heterozygous cells were functionally relatively normal in contrast to the red blood cells from the other hemoglobinopathies studied. Chotivanich et al. (2002) interpreted these findings as suggesting that HbAE erythrocytes have an unidentified membrane abnormality that renders most of the red blood cell population relatively resistant to invasion by P. falciparum. This would not protect from uncomplicated malaria infections but would prevent the development of heavy parasite burdens and was considered consistent with the 'Haldane hypothesis' of heterozygote protection against severe malaria for Hb E.

The Hb E variant is concentrated in parts of Southeast Asia where malaria is endemic, and Hb E carrier status confers some protection against Plasmodium falciparum malaria. To examine the effect of natural selection on the pattern of linkage disequilibrium (LD) and to infer the evolutionary history of the Hb E variant, Ohashi et al. (2004) analyzed biallelic markers surrounding the Hb E variant in a Thai population. Pairwise LD analysis of Hb E and 43 surrounding biallelic markers revealed LD of Hb E extending beyond 100 kb, whereas no LD was observed between non-Hb E variants and the same markers. The inferred haplotype network suggested a single origin of the Hb E variant in the Thai population. Forward-in-time computer simulations under a variety of selection models indicated that the Hb E variant arose 1,240 to 4,440 years ago. Thus, the Hb E mutation occurred recently and allele frequency increased rapidly. The study demonstrated that a high resolution LD map across the human genome can detect recent variants that have been subjected to positive selection.

The highest frequencies of the Hb E gene in large population samples, approximately 0.3, had been observed in the southern part of northeastern Thailand. Even higher frequencies were observed by Flatz et al. (2004) in Austroasiatic populations in southern Laos. One frequency was as high as 0.433 in a population of Sekong Province.

As in other areas of Southeast Asia, hemoglobin E is a very common hemoglobin variant in India, where the highest prevalence of hemoglobin E has been observed in the northeastern regions. In West Bengal, carrier frequency varies from 5 to 35% in different subpopulations, whereas in Assam and Meghalaya, the heterozygous frequency ranges from 27 to 51%. Individuals heterozygous for hemoglobin E have normal or near-normal mean corpuscular volume (MCV) with 27 to 31% of the abnormal Hb in peripheral blood. Homozygosity for hemoglobin E is commonly benign, characterized by mild hypochromic microcytic anemia with the presence of target cells. Edison et al. (2005) observed hyperbilirubinemia among patients with homozygosity for the hemoglobin E gene in the Indian population, with jaundice being the major complaint at presentation. A study of UGT1A1 gene polymorphism showed that the variant TA(7) in the promoter region of the UGT1A1 gene (191740.0011) was associated with hyperbilirubinemia in homozygous HbE patients.

The role of the TA(7) polymorphism of UGT1A1 in the determination of jaundice and gallstones in hemoglobin E beta-thalassemia had been pointed out by Premawardhena et al. (2001) in studies from Sri Lanka. The same group (Premawardhena et al., 2003) studied the global distribution of length polymorphisms of the promoters of the UGT1A1 gene. They found that homozygosity for the TA(7) allele occurred in 10 to 25% of the populations of Africa and the Indian subcontinent, with a variable frequency in Europe. It occurred at a much lower frequency in Southeast Asia, Melanesia, and the Pacific Islands, ranging from 0 to 5%. African populations showed a much greater diversity of length alleles than other populations. These findings defined those populations with a high frequency of hemoglobin E beta-thalassemia and related disorders that are at increased risk for hyperbilirubinemia and gallbladder disease. Beutler et al. (1998) had suggested that the wide diversity in the frequency of the UGT1A1 promoter alleles might reflect a balanced polymorphism mediated through the protective effect of bilirubin against oxidative damage.

O'Donnell et al. (2009) studied Sri Lankan patients with HbE beta-thalassemia for exposure to malaria caused by P. falciparum or P. vivax. They found that there were high frequencies of antibodies to both malaria parasites, as well as DNA-based evidence of current infection with P. vivax. Comparisons with age-matched controls showed that there was a higher frequency of antibodies in thalassemic patients, particularly against P. vivax and in young children, that was unlikely to be related to transfusion. A higher frequency was also found in patients who had undergone splenectomy. O'Donnell et al. (2009) proposed that patients with HbE beta-thalassemia may be more prone to malaria, particularly P. vivax malaria.

The estimated number of worldwide annual births of patients with HbE beta-thalassemia is 19,128 (Modell and Darlison, 2008 and Weatherall, 2010).


.0072   HEMOGLOBIN E (SASKATOON)

HBB, GLU22LYS
SNP: rs33959855, gnomAD: rs33959855, ClinVar: RCV000016333, RCV000757362

See Vella et al. (1967) and Gonzalez-Redondo et al. (1987). Gurgey et al. (1990) found compound heterozygosity for this mutation and beta-thalassemia of type IVS1-6 (141900.0360). Igarashi et al. (1995) identified Hb E-Saskatoon in a Japanese male. Igarashi et al. (1995) reported what they stated was the first case of Hb-E (Saskatoon) in a Japanese male.

Birben et al. (2001) described Hb E-Saskatoon in homozygous state in a 30-year-old Turkish woman. The consanguineous parents were heterozygotes for the abnormal hemoglobin. The heterozygous son of the proband had mild anemia; physical examination of the child and family members revealed no abnormalities. The parameters of routine hematologic studies were within normal limits.


.0073   HEMOGLOBIN EDMONTON

HBB, THR50LYS
ClinVar: RCV000016334

See Labossiere et al. (1971). Landin et al. (1996) pointed out that 2 nucleotide substitutions in codon 50, either ACT to AAA, or ACT to AAG, would be required to produce this amino acid substitution. The same is true for the amino acid substitutions in Hb Bristol (141900.0030) and Hb Beckman (141900.0442) among the beta-globin variants and Hb J-Kurosh (141800.0066), an alpha-globin variant.


.0074   HEMOGLOBIN EXTREMADURA

HBB, VAL133LEU
SNP: rs34095019, ClinVar: RCV000016335

In a Spanish female with mild hemolytic anemia, Villegas et al. (1989) demonstrated this mildly unstable hemoglobin.


.0075   HEMOGLOBIN FANNIN-LUBBOCK

HBB, VAL111LEU AND GLY119ASP
SNP: rs33947020, rs33957964, gnomAD: rs33947020, ClinVar: RCV000016336, RCV000016486, RCV000588047, RCV001811077

See Moo-Penn et al. (1976). In 5 apparently, unrelated Spanish adults, Qin et al. (1994) found a fast-moving hemoglobin variant and observed a GGC-to-GAC mutation at codon 119 which had previously been identified as the abnormality in Hb Fannin-Lubbock. In addition, however, they found a GTC-to-CTC change at codon 111 which led to a val-to-leu substitution. Protein analysis in one of the individuals confirmed that the 2 mutations were located on the same chromosome. Qin et al. (1994) suggested that some other known variants may carry an additional mutation that results in an electrophoretically silent amino acid substitution which may, however, have an effect on the physicochemical properties of the protein. In the case of Hb Fannin-Lubbock, it appeared likely that the val111-to-leu substitution, rather than the gly119-to-asp replacement, was the cause of the instability of the variant. The Hb Fannin-Lubbock variant in these Spanish families had a normal oxygen affinity.


.0076   HEMOGLOBIN FREIBURG

HBB, VAL23DEL
SNP: rs34160180, ClinVar: RCV000016337

Deletion of val23 from otherwise normal beta chain probably occurred through triplet deletion resulting from unequal crossing-over between 2 normal beta loci in 1 parent of the proband. Two of 3 living children of the proband also had the abnormal hemoglobin, which was accompanied by slight cyanosis in all 3 and by a hemolytic process in the proband. See Jones et al. (1966) and Horst et al. (1988).


.0077   HEMOGLOBIN FUKUOKA

HBB, HIS2TYR
SNP: rs35906307, ClinVar: RCV000016339

See Harano et al. (1990).


.0078   HEMOGLOBIN FUKUYAMA

HBB, HIS77TYR
SNP: rs33991294, gnomAD: rs33991294, ClinVar: RCV000016340, RCV001811151, RCV001831569, RCV002281709

See Hidaka et al. (1988).


.0079   HEMOGLOBIN G (ACCRA)

HBB, ASP79ASN
SNP: rs33990858, ClinVar: RCV000016341, RCV000030906, RCV000507382

There is no clinical or hematologic abnormality in the homozygote. See Edington et al. (1955), Gammack et al. (1961), Lehmann et al. (1964), and Milner (1967).


.0080   HEMOGLOBIN G (COPENHAGEN)

HBB, ASP47ASN
SNP: rs33932070, ClinVar: RCV000016342, RCV001284628

See Sick et al. (1967), Schiliro et al. (1981), and Chen et al. (1985).


.0081   HEMOGLOBIN G (COUSHATTA)

HEMOGLOBIN G (SASKATOON)
HEMOGLOBIN G (HSIN-CHU)
HEMOGLOBIN G (TAEGU)
HBB, GLU22ALA
SNP: rs33936254, gnomAD: rs33936254, ClinVar: RCV000016343, RCV000016344, RCV000016345, RCV000016346, RCV000030001, RCV000224041, RCV003226160

See Schneider et al. (1964), Bowman et al. (1967), Vella et al. (1967), Blackwell et al. (1967), Blackwell et al. (1968), Blackwell et al. (1969), Ohba et al. (1978), Niazi et al. (1981), and Dincol et al. (1989).


.0082   HEMOGLOBIN G (FERRARA)

HBB, ASN57LYS
SNP: rs35278874, gnomAD: rs35278874, ClinVar: RCV000016347, RCV001811152

See Giardina et al. (1978).


.0083   HEMOGLOBIN G (GALVESTON)

HEMOGLOBIN G (PORT ARTHUR)
HEMOGLOBIN G (TEXAS)
HBB, GLU43ALA
SNP: rs35262412, ClinVar: RCV000016348, RCV000016349, RCV000016350, RCV000507079, RCV002476973

See Bowman et al. (1962, 1964).


.0084   HEMOGLOBIN G (HSI-TSOU)

HBB, ASP79GLY
SNP: rs34173382, ClinVar: RCV000016351

See Blackwell et al. (1972).


.0085   HEMOGLOBIN G (MAKASSAR)

HBB, GLU6ALA
SNP: rs334, gnomAD: rs334, ClinVar: RCV000016352, RCV003234907

See Blackwell et al. (1970).


.0086   HEMOGLOBIN G (SAN JOSE)

HBB, GLU7GLY
SNP: rs34387455, gnomAD: rs34387455, ClinVar: RCV000016353, RCV000756237, RCV000781437

This hemoglobin oxy was first described in a family of Calabrian origin by Schwartz et al. (1957). The molecular defect was demonstrated by Hill et al. (1960). Brancati et al. (1989) reported a case of homozygosity in a healthy male with normal hematologic findings. See Hill and Schwartz (1959), Ricco et al. (1974), Wilson et al. (1980), and Schiliro et al. (1981).


.0087   HEMOGLOBIN G (SZUHU)

HEMOGLOBIN GIFU
HBB, ASN80LYS
SNP: rs35890380, gnomAD: rs35890380, ClinVar: RCV000016354, RCV000016355

See Blackwell et al. (1969), Imai et al. (1970), Kaufman et al. (1975), Welch (1975) and Romero et al. (1985). Schiliro et al. (1991) found this abnormal hemoglobin in 4 members from 2 generations of a Sicilian family.


.0088   HEMOGLOBIN G (TAIPEI)

HBB, GLU22GLY
SNP: rs33936254, gnomAD: rs33936254, ClinVar: RCV000016356, RCV000756231

See Blackwell et al. (1969), Zeng et al. (1981), and Landman et al. (1987).


.0089   HEMOGLOBIN G (TAIWAN-AMI)

HBB, GLY25ARG
SNP: rs34404985, ClinVar: RCV000016357

See Blackwell and Liu (1968).


.0090   HEMOGLOBIN GAINESVILLE-GA

HBB, GLY46ARG
SNP: rs34743882, ClinVar: RCV000016358

See Chen et al. (1985).


.0091   HEMOGLOBIN GAVELLO

HBB, ASP47GLY
SNP: rs33980484, ClinVar: RCV000016359

See Marinucci et al. (1977).


.0092   HEMOGLOBIN GEELONG

HEMOGLOBIN JINAN
HBB, ASN139ASP
SNP: rs33910475, ClinVar: RCV000016360, RCV000016361

See Como et al. (1984).


.0093   HEMOGLOBIN GENOVA

HEMOGLOBIN HYOGO
HBB, LEU28PRO
SNP: rs33916412, ClinVar: RCV000016362, RCV000016363, RCV001731302

Unstable hemoglobin. See Sansone et al. (1967), Labie et al. (1972), Kendall et al. (1979), Shibata et al. (1980), and Hopmeier et al. (1990).


.0094   HEMOGLOBIN GRANGE-BLANCHE

HBB, ALA27VAL
SNP: rs33954632, gnomAD: rs33954632, ClinVar: RCV000016364, RCV003441719

See Baklouti et al. (1987).


.0095   HEMOGLOBIN GUN HILL

HBB, 15-BP DEL
SNP: rs34210688, ClinVar: RCV000016365

Deletion of amino acid residues 93-97 inclusive of beta chain probably through unequal crossing over. This unstable hemoglobin also has absence of half of the normal complement of heme. Other unstable hemoglobins include Hb Zurich, Hb Koln, Hb Geneva, Hb Sydney, Hb Hammersmith and Hb Sinai. (It is possible that the deletion is 91-95 or 92-96 rather than 93-97.) See Bradley et al. (1967) and Rieder and Bradley (1968). See Hb Koriyama (141900.0152).


.0096   HEMOGLOBIN HACETTEPE

HEMOGLOBIN COMPLUTENSE
HBB, GLN127GLU
SNP: rs33971634, gnomAD: rs33971634, ClinVar: RCV000016366, RCV000016367

See Altay et al. (1976) and Huisman et al. (1986).


.0097   HEMOGLOBIN HAFNIA

HBB, HIS116GLN
SNP: rs35209776, ClinVar: RCV000016368

By isoelectric focusing (IEF) of red cell hemolysates, this hemoglobin variant simulates glycated hemoglobin (HbA1c). This is the first mutation discovered at beta 116. It was first found in a 6-year-old boy with diabetes mellitus; 5 nondiabetic members of the family had the same hemoglobin variant (Blanke et al., 1988). (Hafnia is Latin for Copenhagen.)

During neonatal screening in Belgium, Cotton et al. (2000) found a newborn of Brazilian origin with Hb Hafnia. Both he and his mother were heterozygous for a CAT-to-CAA transversion at codon 116. Both were clinically and hematologically normal.


.0098   HEMOGLOBIN HAMADAN

HBB, GLY56ARG
SNP: rs33935983, gnomAD: rs33935983, ClinVar: RCV000016369, RCV000016553

See Rahbar et al. (1975).

Akar et al. (2003) described the first observation of homozygous Hb Hamadan in a Turkish family. In this family 1 member was a compound heterozygote for Hb Hamadan and beta-thalassemia due to a -29A-G promoter mutation (141900.0379). Neither homozygous Hb Hamadan nor a combination with beta-thalassemia appeared to have clinical significance.


.0099   HEMOGLOBIN HAMILTON

HBB, VAL11ILE
SNP: rs33974228, gnomAD: rs33974228, ClinVar: RCV000016370, RCV000016863, RCV000756241, RCV001104053, RCV001107684, RCV001107685, RCV001107686, RCV001778655, RCV002482873

See Manca et al. (1987) and Wong et al. (1984). Manca et al. (1992) described an easy PCR-based method for demonstration of the mutation. They demonstrated the predicted G-to-A transition at codon 11 which abolishes a MaeIII restriction site. This mutation, which is rather common among Sardinians, involves one of the 5 CpG dinucleotides of the beta-globin gene.


.0100   HEMOGLOBIN HAMMERSMITH

HEMOGLOBIN CHIBA
HEINZ BODY HEMOLYTIC ANEMIA
HBB, PHE42SER
SNP: rs34378160, ClinVar: RCV000016371, RCV000016372, RCV000016373, RCV000757359, RCV001831570

The normal phenylalanine at this site apparently 'stabilizes' the heme with which it is in contact. The substitution of serine leads to severe Heinz body hemolytic anemia. See Dacie et al. (1967), Ohba et al. (1975), and Rahbar et al. (1981). Dianzani et al. (1991) demonstrated a de novo phe42-to-ser mutation using the chemical cleavage of mismatch method (CCM) of Cotton et al. (1988). The responsible substitution was a TTT-to-TCT change. The report of rare cases of this hemoglobinopathy in different ethnic groups also supports the occurrence of independent mutations.


.0101   HEMOGLOBIN HAZEBROUCK

HBB, THR38PRO
SNP: rs34571024, ClinVar: RCV000016374

See Blouquit et al. (1985).


.0102   HEMOGLOBIN HEATHROW

ERYTHROCYTOSIS 6, INCLUDED
HBB, PHE103LEU
SNP: rs35067717, ClinVar: RCV000016375, RCV000641462

Hb Heathrow is a cause of erythrocytosis because of increase in oxygen affinity. The mutation occurs in the same codon as that in Hb Saint Nazaire (141900.0436).

See White et al. (1973).


.0103   HEMOGLOBIN HELSINKI

ERYTHROCYTOSIS 6, INCLUDED
HBB, LYS82MET
SNP: rs33987903, gnomAD: rs33987903, ClinVar: RCV000016376, RCV000641463, RCV001811153

This is a cause of familial erythrocytosis. See Ikkala et al. (1976).


.0104   HEMOGLOBIN HENRI MONDOR

HBB, GLU26VAL
SNP: rs33915112, ClinVar: RCV000016377

See Blouquit et al. (1976) and Bardakdjian et al. (1987).


.0105   HEMOGLOBIN HIJIYAMA

HBB, LYS120GLU
SNP: rs33924134, ClinVar: RCV000016378

See Miyaji et al. (1968).


.0106   HEMOGLOBIN HIKARI

HBB, LYS61ASN
SNP: rs34446260, ClinVar: RCV000016379, RCV003103714, RCV003234908

Heterozygotes have about 60% hemoglobin Hikari. See Shibata and Iuchi (1962) and Shibata et al. (1964).


.0107   HEMOGLOBIN HIMEJI

HBB, ALA140ASP
SNP: rs33927093, ClinVar: RCV000016380, RCV000757357, RCV001277081

This hemoglobin was found in a diabetic because its N-terminal glycation was about 3 times that of the normal (Ohba et al., 1986).


.0108   HEMOGLOBIN HINSDALE

HBB, ASN139LYS
SNP: rs34240441, ClinVar: RCV000016381, RCV003736539

See Moo-Penn et al. (1989).


.0109   HEMOGLOBIN HIROSE

HBB, TRP37SER
SNP: rs33991059, ClinVar: RCV000016382

See Yanase et al. (1968) and Ohba et al. (1983).


.0110   HEMOGLOBIN HIROSHIMA

ERYTHROCYTOSIS 6, INCLUDED
HBB, HIS146ASP
SNP: rs33961444, ClinVar: RCV000016383, RCV000641470

Associated with increased oxygen affinity, decreased Bohr effect, and erythremia. (The substitution was formerly thought to be at residue 143.) See Hamilton et al. (1969) and Perutz et al. (1971).


.0111   HEMOGLOBIN HOFU

HBB, VAL126GLU
SNP: rs121909806, rs33925391, gnomAD: rs33925391, ClinVar: RCV000016384, RCV000759797, RCV001507092

See Miyaji et al. (1968), Brittenham et al. (1978), Ohba et al. (1981), and Arends et al. (1985).


.0112   HEMOGLOBIN HOPE

HBB, GLY136ASP
SNP: rs33949486, gnomAD: rs33949486, ClinVar: RCV000016385, RCV000029996, RCV001004558, RCV001284489, RCV002290955, RCV002321485

See Minnich et al. (1965), Steinberg et al. (1974, 1976), Charache et al. (1979), Harano et al. (1983), Martinez and Colombo (1984), and Enoki et al. (1989). In a Thai Mien family, Pillers et al. (1992) observed Hb Hope in compound heterozygous state with Hb E. Previous reports of Hb Hope had involved predominantly black Americans, blacks who lived in Cuba, or natives of Mali who lived in France.

Ingle et al. (2004) analyzed interactions of Hb Hope with Hb S (141900.0243), other variant hemoglobins, and thalassemia.


.0113   HEMOGLOBIN HOSHIDA

HEMOGLOBIN CHAYA
HBB, GLU43GLN
SNP: rs33922842, gnomAD: rs33922842, ClinVar: RCV000016387

See Iuchi et al. (1978) and Shibata et al. (1980). Plaseska et al. (1991) observed this mutation, due to a GAG-to-CAG change at codon 43, in a Yugoslavian family.


.0114   HEMOGLOBIN HOTEL-DIEU

ERYTHROCYTOSIS 6, INCLUDED
HBB, ASP99GLY
SNP: rs33971048, ClinVar: RCV000016388, RCV000641476

See Blouquit et al. (1981).


.0115   HEMOGLOBIN I (HIGH WYCOMBE)

HBB, LYS59GLU
SNP: rs33969400, ClinVar: RCV000016389

See Boulton et al. (1970), Lacombe et al. (1987), and Wilkinson et al. (1987).

Hamaguchi et al. (2000) reported the first case of hemoglobin I (High Wycombe) in Japan. It was suspected because of a discrepancy between blood glucose status and glycated hemoglobin measurements in a 55-year-old diabetic female.


.0116   HEMOGLOBIN I (TOULOUSE)

HEMOGLOBIN TOULOUSE
HBB, LYS66GLU
SNP: rs34165323, ClinVar: RCV000016390, RCV000985737

See Rosa et al. (1969) and Labie et al. (1971).


.0117   HEMOGLOBIN INDIANAPOLIS

HEINZ BODY HEMOLYTIC ANEMIA
HBB, CYS112ARG
SNP: rs35849199, ClinVar: RCV000016392, RCV000016393

Adams et al. (1978, 1979) studied father and daughter with a clinical picture of beta-thalassemia which was due to labile beta-chains resulting in Heinz body formation in normoblasts. The changes in the beta-chains were posttranslational. Baiget et al. (1986) and De Biasi et al. (1988) described 2 new families with the cys112-to-arg mutation. In these families the carriers were not anemic, had normal chromic and normocytic red cells, and displayed only mild reticulocytosis. This prompted Coleman et al. (1991) to restudy the original family with the finding that the mutation in fact was leu106-to-arg. In order to avoid confusion, they renamed the original mutation Hb Terre Haute (see 141900.0398).


.0118   HEMOGLOBIN ISTANBUL

HEMOGLOBIN SAINT ETIENNE
HBB, HIS92GLN
SNP: rs34083951, gnomAD: rs34083951, ClinVar: RCV000016395

One patient had an apparent new mutation; the father was 41 years old and the mother 36 at the patient's birth (Aksoy et al. (1972)). See Beuzard et al. (1972) and Aksoy and Erdem (1979).

De Weinstein et al. (2000) described this hemoglobin variant in a 36-year-old Argentinian female of Spanish-Portuguese origin. She presented with chronic hemolytic anemia, jaundice, splenomegaly, and gallstones from childhood. She required blood transfusion during her only pregnancy at the age of 23. She underwent splenectomy and cholecystectomy when she was 33 years old. Her 13-year-old son also presented with chronic hemolytic anemia, jaundice, and splenomegaly. It was the third observation of this hemoglobin variant. In the first 2 cases, origination was by de novo mutation. This was the first case in which the precise DNA change was identified: codon 92 was changed from CAC (his) to CAG (gln).


.0119   HEMOGLOBIN J (ALTGELD GARDENS)

HBB, HIS92ASP
SNP: rs33924775, ClinVar: RCV000016396

See Adams et al. (1975, 1978).


.0120   HEMOGLOBIN J (AMIENS)

HBB, LYS17ASN
SNP: rs36006214, ClinVar: RCV000016397

See Elion et al. (1979) and Harano et al. (1990).


.0121   HEMOGLOBIN J (ANTAKYA)

HBB, LYS65MET
SNP: rs33932548, ClinVar: RCV000016398, RCV000016848

See Huisman et al. (1986).


.0122   HEMOGLOBIN J (AUCKLAND)

HBB, GLY25ASP
SNP: rs35474880, ClinVar: RCV000016399

See Williamson et al. (1987).


.0123   HEMOGLOBIN J (BALTIMORE)

HEMOGLOBIN J (IRELAND)
HEMOGLOBIN J (TRINIDAD)
HEMOGLOBIN J (GEORGIA)
HEMOGLOBIN N (NEW HAVEN 2)
HBB, GLY16ASP
SNP: rs33962676, gnomAD: rs33962676, ClinVar: RCV000016400, RCV000508165, RCV000755547

Fast hemoglobin. See Went and MacIver (1959), Gammack et al. (1961), Sydenstricker et al. (1961), Huisman and Sydenstricker (1962), Weatherall (1964), Chernoff and Perillie (1964), Wilkinson et al. (1967), Wong et al. (1971), and Musumeci et al. (1979).


.0124   HEMOGLOBIN J (BANGKOK)

HEMOGLOBIN J (KORAT)
HEMOGLOBIN J (MANADO)
HEMOGLOBIN J (MEINUNG)
HBB, GLY56ASP
SNP: rs34439278, gnomAD: rs34439278, ClinVar: RCV000016405, RCV001811154

See Clegg et al. (1966), Blackwell and Liu (1966), Pootrakul et al. (1967), Blackwell et al. (1970), and Iuchi et al. (1981).


.0125   HEMOGLOBIN J (CAIRO)

HBB, LYS65GLN
SNP: rs35353749, ClinVar: RCV000016409

See Garel et al. (1976).


.0126   HEMOGLOBIN J (CALABRIA)

HEMOGLOBIN J (COSENZA)
HEMOGLOBIN J (BARI)
HBB, GLY64ASP
SNP: rs33922018, ClinVar: RCV000016410, RCV000016411, RCV000016412

See Tentori (1974) and Marinucci et al. (1979).


.0127   HEMOGLOBIN J (CHICAGO)

HBB, ALA76ASP
SNP: rs33985847, gnomAD: rs33985847, ClinVar: RCV000016413

See Romain et al. (1975). This hemoglobin was discovered in a 2-year-old black child from Chicago, who was hospitalized for iron deficiency anemia. The second case was reported in a Spanish family by Arrizabalaga et al. (1998).


.0128   HEMOGLOBIN J (CORDOBA)

HBB, LYS95MET
SNP: rs35204496, ClinVar: RCV000016414

See Bardakdjian et al. (1988).


.0129   HEMOGLOBIN J (DALOA)

HBB, ASN57ASP
SNP: rs33988732, ClinVar: RCV000016415

See Boissel et al. (1982).


.0130   HEMOGLOBIN J (GUANTANAMO)

HBB, ALA128ASP
SNP: rs33957286, ClinVar: RCV000016416

The first reported cases were in a Cuban family of African ancestry (Martinez et al., 1977). Wajcman et al. (1988) described a case from Benin in Nigeria. Also see Zhu et al. (1988) and Sciarratta et al. (1990). Yamagishi et al. (1993) identified this mutation in a Japanese family during assay of glycated hemoglobins by ion exchange high performance liquid chromatography. No anemia or hemolysis was observed in the affected members of the family, although one member had a decreased haptoglobin value.


.0131   HEMOGLOBIN J (IRAN)

HBB, HIS77ASP
SNP: rs33991294, gnomAD: rs33991294, ClinVar: RCV000016417, RCV000985739

See Gammack et al. (1961), Rahbar et al. (1967), and Delanoe-Garin et al. (1986). Bircan et al. (1990) observed compound heterozygosity of this variant with Hb N (Baltimore) (141900.0188).


.0132   HEMOGLOBIN J (KAOHSIUNG)

HEMOGLOBIN J (HONOLULU)
HBB, LYS59THR
SNP: rs35537181, ClinVar: RCV000016418, RCV001284633

See Blackwell et al. (1971) and Blackwell et al. (1972). Chang et al. (1992) described a new RFLP created by this substitution.


.0133   HEMOGLOBIN J (LENS)

HBB, ALA13ASP
SNP: rs35203747, gnomAD: rs35203747, ClinVar: RCV000016420

See Djoumessi et al. (1981).


.0134   HEMOGLOBIN J (LOME)

HBB, LYS59ASN
SNP: rs34621955, gnomAD: rs34621955, ClinVar: RCV000016421, RCV001001409, RCV001272126, RCV001800301

See Wajcman et al. (1977) and Prior et al. (1989).


.0135   HEMOGLOBIN J (LUHE)

HBB, LYS8GLN
SNP: rs33926764, ClinVar: RCV000016422

See Lin et al. (1992).


.0136   HEMOGLOBIN J (RAMBAM)

HEMOGLOBIN J (CAMBRIDGE)
HBB, GLY69ASP
SNP: rs34718174, gnomAD: rs34718174, ClinVar: RCV000016423, RCV001811155

See Salomon et al. (1965) and Sick et al. (1967).

Plaseska-Karanfilska et al. (2000) described Hb Rambam in a family in Argentina. It was combined in compound heterozygous state with a form of beta-zero-thalassemia due to deletion of 2 nucleotides (CT) from codon 5. The latter mutation had been found among Bulgarian, Turkish, Greek, Macedonian, North African, and Middle Eastern populations, and in some populations of the Indian subcontinent.


.0137   HEMOGLOBIN J (SICILIA)

HBB, LYS65ASN
SNP: rs35747961, ClinVar: RCV000016425

See Ricco et al. (1974).


.0138   HEMOGLOBIN J (TAICHUNG)

HBB, ALA129ASP
SNP: rs111645889, gnomAD: rs111645889, ClinVar: RCV000016426, RCV000016429

See Blackwell et al. (1969).


.0139   HEMOGLOBIN JIANGHUA

HBB, LYS120ILE
SNP: rs34303736, ClinVar: RCV000016427

See Lu et al. (1983).


.0140   HEMOGLOBIN JOHNSTOWN

HBB, VAL109LEU
SNP: rs33969677, ClinVar: RCV000016428, RCV001284154

See Jones et al. (1990).

Hb Johnstown, caused by a change of codon 109 in exon 3 of the HBB gene from GTG (val) to CTG (leu) (val109 to leu), is a high oxygen affinity hemoglobin variant. Feliu-Torres et al. (2004) identified Hb Johnstown in association with beta-zero-thalassemia of the IVS1AS-1G-A (141900.0356) type in an 8-year-old girl referred because of erythrocytosis and a left-shifted oxygen dissociation curve. The mother was found to be heterozygous for the Hb variant and the father was a beta-zero-thalassemia carrier. This Hb variant had normal electrophoresis. The erythrocytosis and low values for actual P50 due to Hb Johnstown were more marked due to the coinheritance of the beta-zero-thalassemia.


.0141   HEMOGLOBIN K (CAMEROON)

HBB, ALA129GLU OR ALA129ASP
ClinVar: RCV000016426, RCV000016429

See Allan et al. (1965).


.0142   HEMOGLOBIN K (IBADAN)

HBB, GLY46GLU
SNP: rs35303218, ClinVar: RCV000016430, RCV001811156

See Allan et al. (1965). Castagnola et al. (1990) found this variant in an Italian family.


.0143   HEMOGLOBIN K (WOOLWICH)

HBB, LYS132GLN
SNP: rs33910209, rs33953406, gnomAD: rs33953406, ClinVar: RCV000016431, RCV000780329, RCV001284159

See Allan et al. (1965) and Ringelhann et al. (1971).


.0144   HEMOGLOBIN KAIROUAN

HEMOGLOBIN MONROE
HBB, ARG30THR
SNP: rs33960103, gnomAD: rs33960103, ClinVar: RCV000016432, RCV000506942, RCV001004351, RCV001794452, RCV003338382

Codon 30 (for arginine) is interrupted between the second and third nucleotide by the first intervening sequences of 130 nucleotides. Modifications of the consensus sequence of the donor-splice site of IVS1 will affect the process of splicing. In hemoglobin Monroe, the G-to-C mutation occurred at a nucleotide position adjacent to the GT dinucleotide required for splicing; this substitution would be expected to cause greatly decreased splicing and severe beta-plus-thalassemia, as was observed in the family reported by Gonzalez-Redondo et al. (1989). In a Mediterranean type of beta-plus-thalassemia, Vidaud et al. (1989) found a G-to-C transversion in codon 30 that altered both beta-globin pre-mRNA splicing and the structure of the hemoglobin product. Presumably, this G-to-C transversion at position -1 of intron 1 reduced severely the utilization of the normal 5-prime splice site, since the level of the arg-to-thr mutant hemoglobin (designated hemoglobin Kairouan) was very low in heterozygotes (2% of total hemoglobin). Since no natural mutations of the guanine located at position -1 of the CAG/GTAAGT consensus sequence had been isolated previously, Vidaud et al. (1989) studied the role of this nucleotide in cell-free extracts. They found that correct splicing was 98% inhibited. Thus, the last residue of exon 1 plays a role at least equivalent to that of the intron residue at position 5.


.0145   HEMOGLOBIN KANSAS

HEMOGLOBIN REISSMANN ET AL.
HBB, ASN102THR
SNP: rs33948057, ClinVar: RCV000016434

This hemoglobin variant has a low oxygen affinity, resulting in cyanosis. See Reissmann et al. (1961) and Bonaventura and Riggs (1968).


.0146   HEMOGLOBIN KEMPSEY

ERYTHROCYTOSIS 6, INCLUDED
HBB, ASP99ASN
SNP: rs33954595, ClinVar: RCV000016436, RCV000641495

See Reed et al. (1968).


.0147   HEMOGLOBIN KENITRA

HBB, GLY69ARG
SNP: rs33947415, gnomAD: rs33947415, ClinVar: RCV000016437

See Delanoe-Garin et al. (1985).


.0148   HEMOGLOBIN KHARTOUM

HBB, PRO124ARG
SNP: rs33983276, ClinVar: RCV000016438, RCV000780333

See Clegg et al. (1969).


.0149   HEMOGLOBIN KNOSSOS

BETA-PLUS-THALASSEMIA
BETA-KNOSSOS-THALASSEMIA
HBB, ALA27SER
SNP: rs35424040, gnomAD: rs35424040, ClinVar: RCV000016439, RCV000016440, RCV000016441, RCV000169609, RCV000757368, RCV000780311, RCV001004353

See Arous et al. (1982), Rouabhi et al. (1983), Galacteros et al. (1984), Elwan et al. (1987), and Kutlar et al. (1989). Hemoglobin Knossos is a cause of beta-thalassemia (613985), as is hemoglobin E. Orkin et al. (1984) isolated the beta(Knossos) gene and examined its expression in HeLa cells. Using a cryptic splice sequence that is enhanced by the Knossos substitution, they found that some beta(Knossos) transcripts were abnormally processed. In addition to Hb E, a silent substitution at beta 24 causes thalassemia by abnormal RNA processing.


.0150   HEMOGLOBIN KOFU

HBB, THR84ILE
SNP: rs35914488, ClinVar: RCV000016442

See Harano et al. (1986).


.0151   HEMOGLOBIN KOLN

HEMOGLOBIN UBE-1
HEMOGLOBIN SAN FRANCISCO (PACIFIC)
HEINZ BODY HEMOLYTIC ANEMIA
HBB, VAL98MET
SNP: rs33933298, gnomAD: rs33933298, ClinVar: RCV000016443, RCV000016446, RCV000016807, RCV001811157, RCV001826464

See Shibata et al. (1961), Pribilla (1962), Hutchison et al. (1964), Pribilla et al. (1965), Carrell et al. (1966), Jackson et al. (1967), Jones et al. (1967), Woodson et al. (1970), Miller et al. (1971), Lie-Injo et al. (1972), and Ohba et al. (1973). Bradley et al. (1980) described a convincing instance of gonadal mosaicism accounting for an unusual pedigree pattern in a family with Hb Koln. Normal parents had 2 affected children and each of these 2 children had an affected child. This is the most common form of unstable hemoglobin. Horst et al. (1986) prepared DNA of 19 nucleotides, corresponding in length to the normal and mutant gene sequences, and demonstrated its use for the direct assay of the beta-Koln gene. The use of synthetic oligonucleotides established that the Hb Koln mutation is due to a G-to-A transition.

Landin et al. (1994) found Hb Koln as a new mutation in 3 independent cases of chronic hemolytic anemia in Sweden. The 2 children and 1 adult had partially compensated hemolysis and presented with aggravated hemolysis during acute infections in childhood. In 1 patient, acute B19 parvovirus infection induced an aplastic crisis. Diagnosis was based on hemoglobin instability testing and isoelectric focusing of hemoglobin dimers. Landin et al. (1994) demonstrated that PCR-RFLP can be used in diagnosis.

Chang et al. (1998) reported the first case of Hb Koln in the Chinese population.


.0152   HEMOGLOBIN KORIYAMA

HBB, 15-BP INS
ClinVar: RCV000016447

See Kawata et al. (1988). Whereas 5 amino acid residues are deleted in Hb Gun Hill (141900.0095), 5 amino acid residues are inserted at the corresponding site in Hb Koriyama.


.0153   HEMOGLOBIN KORLE-BU

HBB, ASP73ASN
SNP: rs33945705, gnomAD: rs33945705, ClinVar: RCV000016286, RCV000016449, RCV000587238, RCV000855647, RCV001826465

Since this same substitution is present with the sickle hemoglobin change as one of the two defects in hemoglobin C(Harlem), Konotey-Ahulu et al. (1968) suggested that the latter hemoglobin may have arisen by intracistronic crossing-over in an individual with the Korle-Bu gene on one chromosome and the sickle gene on the other. See Konotey-Ahulu et al. (1968) and Honig et al. (1983). Nagel et al. (1993) showed that compound heterozygosity for hemoglobin Korle-Bu (HbKB) and HbC (141900.0038) is associated with moderate chronic hemolytic anemia with microcytosis. They found that in vitro hemoglobin crystals formed within 2 minutes compared with 30 minutes for a mixture of 40% HbC and 60% HbS and within 180 minutes for 40% HbC with 60% HbA. The crystals were cubic in contrast with the tetragonal crystals observed in CC and SC disease. They concluded that the hemolysis observed in the HbKB/C compound heterozygote is likely to be secondary to the acceleration of Hb crystallization.


.0154   HEMOGLOBIN LA DESIRADE

HBB, ALA129VAL
SNP: rs111645889, gnomAD: rs111645889, ClinVar: RCV000016450, RCV001004559, RCV001284158, RCV001804165

See Merault et al. (1986).


.0155   HEMOGLOBIN LAS PALMAS

HBB, SER49PHE
SNP: rs33960931, ClinVar: RCV000016451, RCV001804737, RCV003476894

See Malcorra-Azpiazu et al. (1988).


.0156   HEMOGLOBIN LEIDEN

HBB, GLU6DEL OR GLU7DEL
SNP: rs63750928, ClinVar: RCV000016452, RCV001800302

See De Jong et al. (1968), Juricic et al. (1983), and Schroeder et al. (1982).


.0157   HEMOGLOBIN LINCOLN PARK

HBB/HBD ANTI-LEPORE
HBB, HBB/HBD FUSION, HBD137DEL
SNP: rs34218295, ClinVar: RCV000016453, RCV000016454

See Honig et al. (1978). A beta-delta (anti-Lepore) variant found in a Mexican family, its amino acid structure of the non-alpha polypeptide indicated a crossover between amino acids 22 and 50. Honig et al. (1978) postulated a series of intergenic crossovers. The residue corresponding to the 137th in the delta chain is deleted. See Hb P(Nilotic).


.0158   HEMOGLOBIN LINKOPING

HEMOGLOBIN MEILAHTI
HBB, PRO36THR
SNP: rs33948615, gnomAD: rs33948615, ClinVar: RCV000016455, RCV000016456

See Jeppsson et al. (1984) and Ali et al. (1988). This variant was detected by oxygen equilibrium measurements and confirmed by IEF in Finns with erythrocytosis (Berlin et al., 1987) and in Americans of Finnish extraction (Jones et al., 1986). Wada et al. (1987) stated that 'in Finland, there are many patients with benign familial erythrocytosis, some of whom have Hb Helsinki' (141900.0103).


.0159   HEMOGLOBIN LITTLE ROCK

ERYTHROCYTOSIS 6, INCLUDED
HBB, HIS143GLN
SNP: rs36020563, gnomAD: rs36020563, ClinVar: RCV000641506

See Bromberg et al. (1973) and Francina et al. (1987). Heterozygotes have marked erythrocytosis as in the case of Hb Chesapeake, J (Capetown), Malmo, Rainier, Bethesda, Yakima, Kempsey, and Hiroshima.


.0160   HEMOGLOBIN LOUISVILLE

HEMOGLOBIN BUCURESTI
HBB, PHE42LEU
SNP: rs33924146, ClinVar: RCV000016458

This hemoglobin shows decreased stability on warming to 65 degrees C and an increased tendency to dissociate in the presence of sulfhydryl group-blocking agents. Clinically, it results in mild hemolytic anemia. See Keeling et al. (1971), Bratu et al. (1971), and Villegas et al. (1989).


.0161   HEMOGLOBIN LUFKIN

HBB, GLY29ASP
SNP: rs35685286, ClinVar: RCV000016460

See Schmidt et al. (1977) and Shimizu et al. (1988). Hb Lufkin is unstable, causing a mild but well-compensated hemolytic anemia. It was initially described in a black American boy from Texas. Gu et al. (1995) found this variant in combination with HbS in a black child who had a mild form of sickle cell disease, comparable to SC or SE disease.


.0162   HEMOGLOBIN LYON

HBB, LYS17DEL AND VAL18DEL
SNP: rs63749958, ClinVar: RCV000016461

Deletion of beta 17-18 (lys-val). See Cohen-Solal et al. (1974).


.0163   HEMOGLOBIN M (MILWAUKEE 1)

METHEMOGLOBINEMIA, BETA TYPE, INCLUDED
HBB, VAL67GLU
SNP: rs33918343, ClinVar: RCV000016462, RCV000641512

For a discussion of methemoglobinemia (617971) caused by Hb M (Milwaukee 1), see Gerald and Efron (1961), Hayashi et al. (1969), Perutz et al. (1972), and Horst et al. (1983). This is now usually called simply Hb M (Milwaukee) since Hb M (Milwaukee-2) has been shown to be the same as Hb M (Hyde Park). The family reported by Pisciotta et al. (1959) was of Italian extraction. Hb M (Milwaukee) was also described in a German family by Kohne et al. (1977). Oehme et al. (1983) followed the mutant beta-globin gene through 3 generations of this family by direct SstI analysis at the gene level. The molecular defect is a transversion T to A and because of the known recognition sequence of SstI, the nucleotide sequence corresponding to amino acids 67 and 68 can be established to be GAGCTC instead of GTGCTC.


.0164   HEMOGLOBIN M (MILWAUKEE 2)

HEMOGLOBIN M (HYDE PARK)
HEMOGLOBIN M (AKITA)
METHEMOGLOBINEMIA, BETA TYPE, INCLUDED
HBB, HIS92TYR
SNP: rs33924775, ClinVar: RCV000016463, RCV000016464, RCV000016465, RCV000641516, RCV003476895

See Pisciotta et al. (1959), Heller et al. (1966), Shibata et al. (1968), and Stamatoyannopoulos et al. (1976). Rotoli et al. (1992) described the case of a cyanotic 7-year-old girl who was found to have 16% methemoglobin (617971). By molecular genetic studies, they demonstrated that this was a case of Hb M (Hyde Park). Hutt et al. (1998) showed by DNA sequence analysis that the mutation in M (Milwaukee-2), M (Hyde Park), and M (Akita) are all due to a change of codon 92 from CAC (his) to TAC (tyr).

Bird et al. (1988) reported a South African family of mixed descent in which 12 individuals with methemoglobin of the Hyde Park type also showed polyagglutination of the red cells. The 40-year-old proband had mild cyanosis and splenomegaly. The characteristics of this form of polyagglutination syndrome had not previously been reported. Red cells did not agglutinate with Arachis hypogea, Dolichos biflorus, or Salvia sclarea, but did show weak agglutination with Salvia horminum and BSII (GSII), and reacted strongly with Glycine soja and Sophora japonica lectins. BSI (GSI) lectin agglutinated group A but not group O cells. Bird et al. (1988) concluded that it was unlikely that this association between polyagglutination and the variant hemoglobin resulted from a single genetic mutation. Rather, the association may have been due to red cell denaturation and abnormal bond formation between this hemoglobin and alpha-sialoglycoprotein molecules in red blood cells.


.0165   HEMOGLOBIN M (SASKATOON)

HEMOGLOBIN M (ARHUS)
HEMOGLOBIN M (CHICAGO)
HEMOGLOBIN M (EMORY)
HEMOGLOBIN M (ERLANGEN)
HEMOGLOBIN M (HAMBURG)
HEMOGLOBIN M (HIDA)
HEMOGLOBIN M (HORLEIN-WEBER)
HEMOGLOBIN M (KURUME)
HEMOGLOBIN M (LEIPZIG)
HEMOGLOBIN M (NOVI SAD)
HEMOGLOBIN M (RADOM) METHEMOGLOBINEMIA, BETA TYPE, INCLUDED
HBB, HIS63TYR
SNP: rs33922873, ClinVar: RCV000016466, RCV000641524, RCV000988480, RCV001266995

This was the abnormal hemoglobin in the family with autosomal dominant cyanosis (617971) reported by Baltzan and Sugarman (1950). See Horlein and Weber (1948), Heck and Wolf (1958), Gerald and George (1959), Gerald and Efron (1961), Shibata et al. (1961, 1965), Heller (1962), Josephson et al. (1962), Hanada et al. (1964), Murawski et al. (1965), Hobolth (1965), Betke et al. (1966), Efremov et al. (1974), Kohne et al. (1975), and Baine et al. (1980). Suryantoro et al. (1995) described the his63-to-tyr mutation in an Indonesian boy with methemoglobinemia and mild hemolysis. The mutation was inherited from the mother. The report further demonstrated the worldwide distribution of Hb M-Saskatoon.


.0166   HEMOGLOBIN MACHIDA

HBB, GLU6GLN
SNP: rs33930165, gnomAD: rs33930165, ClinVar: RCV000016448

See Harano et al. (1982).


.0167   HEMOGLOBIN MADRID

HBB, ALA115PRO
SNP: rs34945623, ClinVar: RCV000016478

The hemoglobin Madrid variant was first discovered by Outeirino et al. (1974) in a Spanish patient whose parents did not carry the abnormality. A second case was observed in an American black teenager by Molchanova et al. (1993); although there was a family history of chronic hemolytic anemia, none of the family members was available for evaluation. Kim et al. (2000) described Hb Madrid in a Korean family with chronic hemolytic anemia. The amino acid substitution was due to a change at codon 115 from GCC (ala) to CCC (pro).


.0168   HEMOGLOBIN MALAY

BETA-PLUS-THALASSEMIA
BETA-MALAY-THALASSEMIA
HBB, ASN19SER
SNP: rs33972047, ClinVar: RCV000016479, RCV000016480, RCV000016481, RCV000020338, RCV000508637, RCV001000121

Yang et al. (1989) found an A-to-G change in codon 19 resulting in beta-plus-thalassemia (613985) in a Malaysian.


.0169   HEMOGLOBIN MALMO

ERYTHROCYTOSIS 6, INCLUDED
HBB, HIS97GLN
SNP: rs34515413, gnomAD: rs34515413, ClinVar: RCV000016482, RCV000641527

See Lorkin and Lehmann (1970), Fairbanks et al. (1971), Boyer et al. (1972), Berglund (1972), and Berglund and Linell (1972).

Landin et al. (1996) found this hemoglobin variant with increased oxygen affinity causing erythrocytosis in 2 apparently unrelated Swedish families. In 1 family, the his97-to-gln substitution was caused by a change from CAC-to-CAA; in the other family a CAC-to-CAG change was found.


.0170   HEMOGLOBIN MAPUTO

HBB, ASP47TYR
SNP: rs33932070, ClinVar: RCV000016483

See Marinucci et al. (1983).


.0171   HEMOGLOBIN MARSEILLE

HEMOGLOBIN LONG ISLAND
HBB, NH2 EXTENSION, HIS2PRO
SNP: rs33983205, gnomAD: rs33983205, ClinVar: RCV000016485

In this abnormal hemoglobin, found by isoelectric focusing in a hematologically normal though diabetic Maltese woman living in Marseille, Blouquit et al. (1984, 1985) demonstrated a double abnormality: a methionyl residue extending the NH2 terminus. This is an example of the increasing number of hemoglobin variants detected in the course of HbA1c evaluation in diabetics. Without DNA data, the authors concluded that proline in position 2 constitutes a steric impairment to the methionyl peptidase that normally eliminates the initiating methionine. The same hypothesis has been invoked to explain the apparent persistence of the initiator methionyl residue in naturally occurring proteins with a met-X sequence at the NH2-terminus, X being either a charged amino acid or a proline. Initial sequence, with abnormal residues in parentheses, equals H2N-(met)-val-(pro)-leu-thr-glu-glu-. Prchal et al. (1986) showed that the only lesion in DNA is an adenine-to-cytosine transversion in the second codon. Also see Barwick et al. (1985). Boi et al. (1989) detected this variant in Australia in the course of monitoring glycated hemoglobin (HbA1c) in diabetics. It causes a discrepancy between the HbA1c measurement and the clinical state of the diabetic patient.


.0172   HEMOGLOBIN MASUDA

HBB, LEU114MET AND GLY119ASP
SNP: rs33917394, gnomAD: rs33917394, ClinVar: RCV000016336, RCV000016486, RCV000016745, RCV000588047

See Ohba et al. (1989).


.0173   HEMOGLOBIN MATERA

HBB, MET55LYS
SNP: rs35094013, ClinVar: RCV000016487

Sciarratta and Ivaldi (1990) discovered this electrophoretically slow-moving variant in an Italian family. Numerous red cells contained inclusion bodies, and heat and isopropanol tests demonstrated decreased stability of the hemoglobin.


.0174   HEMOGLOBIN MEQUON

HBB, PHE41TYR
SNP: rs33926796, ClinVar: RCV000016488

See Buckett et al. (1974).


.0175   HEMOGLOBIN MCKEES ROCKS

ERYTHROCYTOSIS 6, INCLUDED
HBB, TYR145TER
SNP: rs35291591, ClinVar: RCV000016489, RCV000641529

The beta chain is only 144 amino acids long. The codon for beta 145 tyr has been changed to a terminator. Polycythemia is the clinical manifestation. See Winslow et al. (1975) and Rahbar et al. (1983).


.0176   HEMOGLOBIN MINNEAPOLIS-LAOS

HBB, PHE118TYR
SNP: rs33928092, ClinVar: RCV000016490

See Hedlund et al. (1984).


.0177   HEMOGLOBIN MISSISSIPPI

HEMOGLOBIN MS
HBB, SER44CYS
SNP: rs34868397, ClinVar: RCV000016491, RCV001811158

See Adams et al. (1985). Hemoglobin Mississippi has anomalous properties that include disulfide linkages with normal beta-, delta-, gamma-, and alpha-chains, and the formation of high molecular weight multimers. Heterozygotes for Hb MS are clinically and hematologically normal and heterozygotes for the beta-plus-thalassemia gene have mild microcytic anemia; however, the proband in the family initially discovered by Steinberg et al. (1987) had all the hematologic features of thalassemia intermedia in the compound heterozygous state. Steinberg et al. (1987) suggested that the unexpectedly severe clinical expression in the mixed heterozygote, as they called the state, may result from the proteolytic digestion of Hb MS as well as the excessive alpha-chains characteristic of beta-plus-thalassemia.


.0178   HEMOGLOBIN MITO

HBB, LYS144GLU
SNP: rs33964352, ClinVar: RCV000016493

See Harano et al. (1985).


.0179   HEMOGLOBIN MIYADA

HBB/HBD ANTI-LEPORE
HBB, HBB/HBD FUSION
ClinVar: RCV000016494, RCV000016495

This is a beta-delta fusion variant, the complement of hemoglobin Lepore. For explanation, see hemoglobin P (Congo) (141900.0214). From a DNA sequence analysis of the Hb Miyada gene, Kimura et al. (1984) concluded that the shift from the 5-prime beta-globin gene to the 3-prime delta-globin gene occurred somewhere in a homologous sequence region between the third nucleotide of codon 17 and the second nucleotide of codon 21 of these 2 genes.


.0180   HEMOGLOBIN MIYASHIRO

HBB, VAL23GLY
SNP: rs33945546, ClinVar: RCV000016496

See Nakatsuji et al. (1981) and Ohba et al. (1984).


.0181   HEMOGLOBIN MIZUHO

HBB, LEU68PRO
SNP: rs33972593, ClinVar: RCV000016497, RCV003447476

See Ohba et al. (1977). Keeling et al. (1991) observed this variant in a Caucasian boy from Kentucky.

As noted by Harthoorn-Lasthuizen et al. (1995), Hb Mizuho is one of the more markedly unstable hemoglobin variants and is difficult to detect both by protein analysis and by sequencing of the amplified beta chain. The instability is due to the introduction of a proline residue in helix E, of which 5 residues form part of the heme contact. Harthoorn-Lasthuizen et al. (1995) identified a fourth case in a Dutch boy.


.0182   HEMOGLOBIN MIZUNAMI

HBB, PHE83SER
SNP: rs1803195, gnomAD: rs1803195, ClinVar: RCV000016498

See Shibata et al. (1980).


.0183   HEMOGLOBIN MOBILE

HBB, ASP73VAL
SNP: rs33967755, ClinVar: RCV000016499

See Schneider et al. (1975) and Converse et al. (1985).


.0184   HEMOGLOBIN MORIGUCHI

HBB, HIS97TYR
SNP: rs33950993, ClinVar: RCV000016500

See Ohba et al. (1989).


.0185   HEMOGLOBIN MOSCVA

HBB, GLY24ASP
SNP: rs33968721, ClinVar: RCV000016501

See Idelson et al. (1974).


.0186   HEMOGLOBIN MOZHAISK

HBB, HIS92ARG
SNP: rs33974325, ClinVar: RCV000016502

See Spivak et al. (1982).


.0187   HEMOGLOBIN N, BETA TYPE

HBB, LYS95ASP
ClinVar: RCV000016503

Fast hemoglobin. See Ager and Lehmann (1958), Chernoff and Weichselbaum (1958), and Gammack et al. (1961).


.0188   HEMOGLOBIN N (BALTIMORE)

HEMOGLOBIN N (JENKINS)
HEMOGLOBIN JENKINS
HEMOGLOBIN HOPKINS 1
HEMOGLOBIN KENWOOD
HBB, LYS95GLU
SNP: rs33914359, gnomAD: rs33914359, ClinVar: RCV000016251, RCV000016504, RCV000016505, RCV000016506, RCV000016507, RCV000016508, RCV000506157, RCV000755549, RCV001835628

See Clegg et al. (1965), Dobbs et al. (1966), Gottlieb et al. (1967), Ballas and Park (1985), and Anderson Fernandes (1989). In heterozygotes the concentration of Hb N (Baltimore) is the same as that of HbA. Hemoglobin Kenwood was previously reported incorrectly as having either aspartic acid or glutamic acid at beta 143. See personal communication from Heller in Hamilton et al. (1969).


.0189   HEMOGLOBIN N (MEMPHIS)

HBB, LYS95GLX
ClinVar: RCV000016509

See Schroeder and Jones (1965).


.0190   HEMOGLOBIN N (SEATTLE)

HBB, LYS61GLU
SNP: rs33995148, ClinVar: RCV000016510, RCV001811159, RCV001826466

See Jones et al. (1968).


.0191   HEMOGLOBIN N (TIMONE)

HBB, LYS8GLU
SNP: rs33926764, ClinVar: RCV000016511, RCV001269803

See Lena-Russo et al. (1989).


.0192   HEMOGLOBIN NAGASAKI

HBB, LYS17GLU
SNP: rs33986703, gnomAD: rs33986703, ClinVar: RCV000016512

See Maekawa et al. (1970). Nakamura et al. (1997) identified a second case in a Japanese family. The proband was a 47-year-old diabetic male. The anomaly was identified during the HPLC assay for HBA1c. The abnormal beta chain comprised about 44% of the total beta chain as opposed to 30% in the previous report.


.0193   HEMOGLOBIN NAGOYA

HBB, HIS97PRO
SNP: rs33951978, ClinVar: RCV000016513

Hb Nagoya is an unstable hemoglobin found in father and son in Japan (Ohba et al., 1985).


.0194   HEMOGLOBIN NEVERS

HBB, TYR130SER
SNP: rs33937535, ClinVar: RCV000016514

During an investigation for erythrocytosis, Keclard et al. (1990) found this electrophoretically silent beta chain variant in a French-Caucasian male. The sister, mother, and grandmother carried the same abnormal hemoglobin in heterozygous state. The mother showed mild erythrocytosis.


.0195   HEMOGLOBIN NEW MEXICO

HBB, PRO100ARG
SNP: rs33965000, ClinVar: RCV000016515, RCV001811160

See Moo-Penn et al. (1985).


.0196   HEMOGLOBIN NEW YORK

HEMOGLOBIN KAOHSIUNG
HBB, VAL113GLU
SNP: rs34484056, gnomAD: rs34484056, ClinVar: RCV000016516, RCV001284155

This variant was found in a Chinese-American family. See Ranney et al. (1967), Kendall and Pang (1980), Saenz et al. (1980), and Todd et al. (1980).


.0197   HEMOGLOBIN NEWCASTLE

HBB, HIS92PRO
SNP: rs33974325, ClinVar: RCV000016518, RCV000016780

See Finney et al. (1975).


.0198   HEMOGLOBIN NITEROI

HBB, PHE42DEL, GLU43DEL, SER44DEL
SNP: rs35637840, ClinVar: RCV000016519

Deletion of phenylalanine, glutamic acid and serine at either beta 42-44 or beta 43-45. See Praxedes et al. (1972).


.0199   HEMOGLOBIN NORTH CHICAGO

HBB, PRO36SER
SNP: rs33948615, gnomAD: rs33948615, ClinVar: RCV000016520

Increased oxygen affinity. Discovered in a 52-year-old man treated since age 20 years for polycythemia vera with various measures including several courses of 32(P) (Rahbar et al., 1985).


.0200   HEMOGLOBIN NORTH SHORE

HEMOGLOBIN NORTH SHORE-CARACAS
HBB, VAL134GLU
SNP: rs33966761, gnomAD: rs33966761, ClinVar: RCV000016521

See Arends et al. (1977), Brennan et al. (1977), Adams et al. (1982), and Gurney et al. (1987).


.0201   HEMOGLOBIN NOTTINGHAM

HBB, VAL98GLY
SNP: rs33985510, ClinVar: RCV000016523

See Gordon-Smith et al. (1973) and Orringer et al. (1978). The patient of Orringer et al. (1978) was a 7-year-old boy with severe hemolytic anemia in whom great improvement in clinical status, including rate of growth, was noted 1 year after he underwent a splenectomy and cholecystectomy. Cepreganova et al. (1992) described severe hemolytic anemia in a 7-year-old Canadian boy with Hb Nottingham. Brabec et al. (1994) reported a fourth case in an 8-year-old girl in the Czech Republic with severe hemolytic anemia.


.0202   HEMOGLOBIN O (ARAB)

HEMOGLOBIN EGYPT
HBB, GLU121LYS
SNP: rs33946267, gnomAD: rs33946267, ClinVar: RCV000016524, RCV000016525, RCV000016577, RCV000016863, RCV000029993, RCV000202511, RCV000508438, RCV000587075, RCV002476974

This hemoglobin has been found in American blacks, Bulgarians, and Arabs (Kamel et al., 1967). Little et al. (1980) illustrated the fact that point mutation can be recognized by the change in susceptibility to cleavage by specific restriction endonucleases. The examples were: Hb O(Arab) with EcoRI, Hb J(Broussais) with HindIII, and Hb F(Hull) with EcoRI. The sickle cell mutation eliminates a site for MnlI. See Ramot et al. (1960), Kamel et al. (1967), Vella et al. (1966), Milner et al. (1970), and Charache et al. (1977).


.0203   HEMOGLOBIN OCHO RIOS

HBB, ASP52ALA
SNP: rs33919924, ClinVar: RCV000016526

See Beresford et al. (1972).


.0204   HEMOGLOBIN OHIO

ERYTHROCYTOSIS 6, INCLUDED
HBB, ALA142ASP
SNP: rs33921821, ClinVar: RCV000016527, RCV000641554

High oxygen affinity leads to erythrocytosis. See Moo-Penn et al. (1980).


.0205   HEMOGLOBIN OKALOOSA

HBB, LEU48ARG
SNP: rs33952850, ClinVar: RCV000016528

See Charache et al. (1973).


.0206   HEMOGLOBIN OKAYAMA

HBB, HIS2GLN
SNP: rs713040, gnomAD: rs713040, ClinVar: RCV000016529, RCV003736540

See Harano et al. (1983).


.0207   HEMOGLOBIN OKAZAKI

HBB, CYS93ARG
SNP: rs33972927, ClinVar: RCV000016530, RCV000016758

See Harano et al. (1984).


.0208   HEMOGLOBIN OLMSTED

HBB, LEU141ARG
SNP: rs35854892, ClinVar: RCV000016531, RCV003476896

See Fairbanks et al. (1969) and Lorkin and Lehmann (1970). Thuret et al. (1996) described a second case of this unstable hemoglobin. The clinical course of a 12-year-old boy was characterized by severe hemolytic anemia leading to splenectomy and cholecystectomy at the age of 3.5 years. Priapism occurred 8 years after splenectomy, during a hemolytic febrile episode, and required aspiration of the corpora cavernosa. Splenectomy in cases of chronic hemolytic anemia due to an unstable hemoglobin lowers the frequency and severity of acute hemolytic attacks but vascular complications often occur. The original patient with Hb Olmsted, described by Fairbanks et al. (1969) died of chronic pulmonary disease with pulmonary hypertension at age 36 years. The patient reported by Thuret et al. (1996) had a French mother and Spanish father.


.0209   HEMOGLOBIN OLOMOUC

HBB, ALA86ASP
SNP: rs35819837, gnomAD: rs35819837, ClinVar: RCV000016532

This beta-chain variant, associated with erythrocytosis, was first discovered in a member of a Czechoslovakian family (Indrak et al., 1987). Tagawa et al. (1992) found the same mutation in a Japanese family.


.0210   HEMOGLOBIN OLYMPIA

ERYTHROCYTOSIS 6, INCLUDED
HBB, VAL20MET
SNP: rs35890959, gnomAD: rs35890959, ClinVar: RCV000016533, RCV000641556, RCV000759801, RCV002496379

Since GUG to AUG is the only single base change that can result in this substitution, the codon for beta 20 can be uniquely identified as GUG. See Stamatoyannopoulos et al. (1973) and Weaver et al. (1984). Berlin and Wranne (1989) described hemoglobin Olympia in a Swedish family.


.0211   HEMOGLOBIN OSLER

HEMOGLOBIN NANCY
HEMOGLOBIN FORT GORDON
ERYTHROCYTOSIS 6, INCLUDED
HBB, TYR145ASN-TO-ASP
SNP: rs33949869, ClinVar: RCV000781441, RCV001839458

Compensatory erythrocytosis results from its high oxygen affinity. See Charache et al. (1975), Gacon et al. (1975), Kleckner et al. (1975), and Butler et al. (1982).

Kattamis et al. (1997) found hemoglobin Osler in 2 members of an African American family with erythrocytosis. Sequence analysis of DNA from the proband showed heterozygosity for a T-to-A transversion at the first position of codon 145 in the HBB gene, which resulted in the substitution of an asparagine for normal tyrosine. The second cycle of C-terminal amino acid sequence analysis of a mixture of alpha- and beta-globin chains showed tyrosine, aspartic acid, and small amounts of asparagine. Collectively, these results were interpreted as indicating the existence of a mutation at codon 145 of the HBB gene, which codes for asparagine instead of tyrosine, and that asparagine then undergoes initial posttranslational deamidation to aspartic acid. Thus the mutation is tyr145asn, not tyr145asp, as initially thought. Posttranslational modifications had been described in 4 other beta-globin chains and 2 alpha-globin chain variants: Hb Providence (141900.0227), Hb Redondo, or Isehara (141900.0404), Hb La Roche-sur-Yon (141900.0482), Hb J (Singapore) (141800.0075), Hb Wayne (141850.0004), and the only variant in which the posttranslational modification does not involve an asn-to-asp substitution, Hb Bristol (val167met-asp; 141900.0030).


.0212   HEMOGLOBIN OSU CHRISTIANSBORG

HBB, ASP52ASN
SNP: rs33961886, gnomAD: rs33961886, ClinVar: RCV000016537, RCV000016759, RCV000029964, RCV001811161

Konotey-Ahulu et al. (1971) first observed this nonpathologic mutant in a Ghanaian patient with Hb S (141900.0243). By molecular analysis of the HBB gene, Giordano et al. (1999) identified the same mutant in 2 unrelated families of African origin living in the Netherlands, one from Ghana and the other from the Dominican Republic. In all carriers of both families, the mutation was associated with haplotype 11, an infrequent haplotype in the West African population, suggesting a single common mutation event. Giordano et al. (1999) stated that because Hb Osu-Christiansborg migrates at a similar rate to that of Hb S in alkaline hemoglobin electrophoresis, it can easily be mistaken for Hb S.

Hb Osu-Christiansborg has been described in several parts of the world and the mutation is believed to have had independent origins in these cases. Rodrigues de Souza et al. (2004) reported the first case of Hb Osu-Christiansborg in Brazil. The patient was a healthy 10-year-old boy, descendant of Spanish and Brazilian Native Indians. Hematologic data were all normal. The mutation was not found in the parents. Paternity testing confirmed the biologic relationship between the parents and the child, demonstrating that this was a de novo mutation.


.0213   HEMOGLOBIN P

HEMOGLOBIN P (GALVESTON)
HBB, HIS117ARG
SNP: rs33935673, rs33978082, gnomAD: rs33978082, ClinVar: RCV000016538, RCV000016539

See Silvestroni et al. (1963), Schneider et al. (1969), and Di Iorio et al. (1975).


.0214   HEMOGLOBIN P (CONGO)

HBB/HBD ANTI-LEPORE
HBB, HBB/HBD FUSION
ClinVar: RCV000016540

This is a beta-delta fusion variant, the complement of hemoglobin Lepore. Unlike the delta-beta fusion product of Lepore hemoglobin, the non-alpha chain resembles beta at the NH2-end. Furthermore, HbA2 is present in normal concentrations and both HbA and HbS (or other beta variant) can be present in the patient heterozygous for hemoglobin P (Congo). The explanation for the origin of hemoglobin Lepore and hemoglobin P (Congo) (nonhomologous pairing and unequal crossing-over) is diagrammed in Fig. 2.20 (p. 41) of McKusick (1969). The fusion occurs between beta 22 and delta 116 (Lehmann and Charlesworth, 1970). See Dherte et al. (1959), Lehmann et al. (1964), Lambotte-Legrand et al. (1960), and Gammack et al. (1961).


.0215   HEMOGLOBIN P (NILOTIC)

HBB/HBD ANTI-LEPORE
HBB, HBB/HBD FUSION
ClinVar: RCV000016542, RCV000016543

This is a beta-delta fusion product like Hb P (Congo) and Hb Miyada. The fusion site is beta 22 to delta 50. Thus, Hb P(Nilotic) is identical to Hb Lincoln Park (141900.0157) except for deletion of delta residue 137 in Hb Lincoln Park. Thus, it is the complement of Hb Lepore (Hollandia). See Badr et al. (1973). Among 8 chromosomes carrying the Hb P (Nilotic) hybrid gene, Lanclos et al. (1987) found only 1 haplotype.


.0216   HEMOGLOBIN PALMERSTON NORTH

ERYTHROCYTOSIS 6, INCLUDED
HBB, VAL23PHE
SNP: rs33929459, gnomAD: rs33929459, ClinVar: RCV000016544, RCV000641570

See Brennan et al. (1982).


.0217   HEMOGLOBIN PASADENA

HBB, LEU75ARG
SNP: rs33950542, ClinVar: RCV000016545

See Johnson et al. (1980) and Rahbar et al. (1988).


.0218   HEMOGLOBIN PERTH

HEMOGLOBIN ABRAHAM LINCOLN
HEMOGLOBIN KOBE
HBB, LEU32PRO
SNP: rs33920173, rs33948578, ClinVar: RCV000016546, RCV000016547, RCV000016548, RCV003480032

This is an unstable hemoglobin resulting in hemolytic anemia. See Jackson et al. (1973), Honig et al. (1973), Rousseaux et al. (1980), and Shibata et al. (1980).


.0219   HEMOGLOBIN PETERBOROUGH

HBB, VAL111PHE
SNP: rs33957964, ClinVar: RCV000016549

See King et al. (1972).

Nakanishi et al. (1998) provided the second report of Hb Peterborough and the first of its occurrence in Japan.


.0220   HEMOGLOBIN PHILLY

HBB, TYR35PHE
SNP: rs35857380, ClinVar: RCV000016550

An unstable hemoglobin leading to hemolytic anemia. No electrophoretic abnormality. See Rieder et al. (1969) and Asakura et al. (1981).


.0221   HEMOGLOBIN PIERRE-BENITE

HBB, GLU90ASP
SNP: rs35002698, ClinVar: RCV000016551, RCV003387724

See Baklouti et al. (1988).


.0222   HEMOGLOBIN PITIE-SALPETRIERE

ERYTHROCYTOSIS 6, INCLUDED
HBB, VAL34PHE
SNP: rs1141387, ClinVar: RCV000016552, RCV000641578, RCV001284488

Associated with erythrocytosis. See Blouquit et al. (1980).


.0223   HEMOGLOBIN POISSY

HBB, GLY56ARG AND ALA86PRO
SNP: rs33935983, rs33952147, gnomAD: rs33935983, rs33952147, ClinVar: RCV000016369, RCV000016553, RCV000016878

See Lacombe et al. (1985).


.0224   HEMOGLOBIN PORTO ALEGRE

HBB, SER9CYS
SNP: rs33918131, gnomAD: rs33918131, ClinVar: RCV000016556, RCV000508345, RCV000985743

This hemoglobin has an extra reactive thiol group because of the substitution of cysteine for serine. Octamers and dodecamers form in hemolysates of heterozygotes and homozygotes, respectively, on standing, through linkage between tetramers by disulfide bridges. See Tondo et al. (1963), Bonaventura and Riggs (1967), Seid-Akhavan et al. (1973), and Tondo (1976).

Salzano (2000) tabulated the Hbb variants observed in Latin America and provided further information on Hb Porto Alegre, which had been discovered by his group in a family of Portuguese descent living in the Brazilian city of that name. Substitution of cysteine for serine at the ninth residue of the chain created a sulfhydryl group on the surface of the molecule, allowing formation of intermolecular disulfide bonds. However, polymerization occurs in vitro but not in vivo, and the variant hemoglobin leads to no clinical problems. Lack of polymerization in vivo may be because of a compensatory synthesis of glutathione reductase.


.0225   HEMOGLOBIN POTOMAC

ERYTHROCYTOSIS 6, INCLUDED
HBB, GLU101ASP
SNP: rs35209591, gnomAD: rs35209591, ClinVar: RCV000016557, RCV000641582

See Charache et al. (1978) and Lacombe et al. (1987).


.0226   HEMOGLOBIN PRESBYTERIAN

HBB, ASN108LYS
SNP: rs34933751, gnomAD: rs34933751, ClinVar: RCV000016558

See Moo-Penn et al. (1978), Horst et al. (1983), and Villegas et al. (1986). Using PCR and direct sequencing, Schnee et al. (1990) demonstrated that the molecular defect is a C-to-G substitution in codon 108; this eliminates an MaeII restriction site.

The beta variant lys108 enhances the stability of hemoglobin in the deoxy-state, conferring low affinity for oxygen binding in vitro. Suzuki et al. (2002) generated mutant mice carrying the Presbyterian mutation at the beta-globin locus by a targeted knockin strategy. Heterozygous mice showed the expression of Hb Presbyterian in 27.7% of total peripheral blood without any hematologic abnormalities, which well mimicked human cases. On the other hand, homozygous mice exclusively expressed Hb Presbyterian in 100% of peripheral blood associated with hemolytic anemia, Heinz body formation, and splenomegaly. Hb Presbyterian showed instability in an in vitro precipitation assay. Erythrocytes from homozygous mice showed a shortened life span when transfused into wildtype mice, confirming that the knocked-in mutation of lys108 caused hemolysis in homozygous mice. Suzuki et al. (2002) stated that this was the first report on the hemolytic anemia of unstable hemoglobin in an animal model. The results confirmed the notion that the higher ratio of an unstable variant beta-globin chain in erythrocytes triggers the pathologic precipitation and induces hemolysis in abnormal hemoglobinopathies.


.0227   HEMOGLOBIN PROVIDENCE

ERYTHROCYTOSIS 6, INCLUDED
HBB, LYS82ASX
SNP: rs33991993, gnomAD: rs33991993, ClinVar: RCV000016559, RCV000016579, RCV000641585

See Moo-Penn et al. (1976), Charache et al. (1977), and Bardakdjian et al. (1985).


.0228   HEMOGLOBIN PYRGOS

HBB, GLY83ASP
SNP: rs1803195, gnomAD: rs1803195, ClinVar: RCV000016560, RCV001811162, RCV003234909

See Tatsis et al. (1972) and Yamada et al. (1977). Schiliro et al. (1991) found this hemoglobin variant in a mother and son in Sicily who were both clinically and hematologically normal.


.0229   HEMOGLOBIN QUIN-HAI

HBB, LEU78ARG
SNP: rs34870172, ClinVar: RCV000016554

See Jen et al. (1983).


.0230   HEMOGLOBIN RADCLIFFE

ERYTHROCYTOSIS 6, INCLUDED
HBB, ASP99ALA
SNP: rs33971048, ClinVar: RCV000016555, RCV000641589

Cause of polycythemia. See Weatherall et al. (1977).


.0231   HEMOGLOBIN RAHERE

ERYTHROCYTOSIS 6, INCLUDED
HBB, LYS82THR
SNP: rs33987903, gnomAD: rs33987903, ClinVar: RCV000016561, RCV000641593

See Lorkin et al. (1975) and Sugihara et al. (1985). Beta 82 is at the binding site of 2,3-diphosphoglycerate. Hb Rahere is accompanied by erythrocytosis.


.0232   HEMOGLOBIN RAINIER

ERYTHROCYTOSIS 6, INCLUDED
HBB, TYR145CYS
SNP: rs35117167, ClinVar: RCV000016562, RCV000641598, RCV001284491

See Stamatoyannopoulos et al. (1968), Adamson et al. (1969), Stamatoyannopoulos and Yoshida (1969), Greer and Perutz (1971), Hayashi et al. (1971), and Salhany (1972). Hb Rainier causes erythrocytosis and is the only adult hemoglobin that is alkali-resistant. See Hb Bethesda (141900.0022), with which Rainier was confused earlier. Peters et al. (1985) studied a hemoglobin mutation induced by ethylnitrosourea in the mouse. Substitution of cysteine for tyrosine at codon 145 of the HBB gene was demonstrated by amino acid analysis. They proposed that an A-to-G transition in the tyrosine codon (TAC-to-TGC) had occurred. The mouse was polycythemic.

Carbone et al. (1999) identified a high oxygen affinity hemoglobin variant in a 53-year-old male from Naples, Italy, who suffered from pulmonary thromboembolism and polycythemia. Characterization of this variant at the protein level detected the presence of Hb Rainier. The mutation resulted from an A-to-G transition at the second position of codon 145 of the HBB gene, resulting in a tyr145-to-cys substitution.


.0233   HEMOGLOBIN RALEIGH

HBB, VAL1ALA
SNP: rs33949930, gnomAD: rs33949930, ClinVar: RCV000016563, RCV000781459, RCV001811163, RCV001831571

Substitution of acetylalanine for valine at beta 1. See Moo-Penn et al. (1977).

This variant was numbered based on the first amino acid of the mature protein. In the gene-based system of counting, this variant is VAL2ALA.


.0234   HEMOGLOBIN RANDWICK

HBB, TRP15GLY
SNP: rs121909807, rs33946157, gnomAD: rs33946157, ClinVar: RCV000016564

See Gilbert et al. (1988).


.0235   HEMOGLOBIN REGINA

HBB, LEU96VAL
SNP: rs34665886, ClinVar: RCV000016565

See Devaraj et al. (1985). Bisse et al. (1991) reported the second affected family. The hemoglobin variant was associated with high oxygen affinity and erythrocytosis.


.0236   HEMOGLOBIN RICHMOND

HBB, ASN102LYS
SNP: rs34227486, ClinVar: RCV000016566

See Efremov et al. (1969) and Winslow and Charache (1975).


.0237   HEMOGLOBIN RIO GRANDE

HBB, LYS8THR
SNP: rs33932981, ClinVar: RCV000030668

See Moo-Penn et al. (1983).


.0238   HEMOGLOBIN RIVERDALE-BRONX

HBB, GLY24ARG
SNP: rs33972975, ClinVar: RCV000016567

See Ranney et al. (1968).


.0239   HEMOGLOBIN RIYADH

HEMOGLOBIN KARATSU
HBB, LYS120ASN
SNP: rs34726542, gnomAD: rs34726542, ClinVar: RCV000016568, RCV000589733

See Budge et al. (1977), El-Hazmi and Lehmann (1977), Miyaji et al. (1977), and Pinkerton et al. (1979).


.0240   HEMOGLOBIN ROSEAU-POINTE A PITRE

HBB, GLU90GLY
SNP: rs35068498, ClinVar: RCV000016570

See Merault et al. (1985).


.0241   HEMOGLOBIN ROTHSCHILD

HBB, TRP37ARG
SNP: rs33994623, ClinVar: RCV000016571

See Gacon et al. (1977) and Danish et al. (1982). Kavanaugh et al. (1992) reported x-ray crystallographic studies.


.0242   HEMOGLOBIN RUSH

HBB, GLU101GLN
SNP: rs33966487, ClinVar: RCV000016572

See Adams et al. (1974).


.0243   HEMOGLOBIN S

SICKLE CELL DISEASE, INCLUDED
MALARIA, RESISTANCE TO, INCLUDED
HBB, GLU6VAL
SNP: rs334, gnomAD: rs334, ClinVar: RCV000016286, RCV000016573, RCV000016574, RCV000016575, RCV000016576, RCV000016577, RCV000016579, RCV000016580, RCV000016877, RCV000016879, RCV000030905, RCV000224000, RCV000477892, RCV000576548, RCV000623118, RCV000723337, RCV001192494, RCV001255121, RCV001535873, RCV001824571, RCV002251908, RCV002288496, RCV003150808, RCV003407340

The change from glutamic acid to valine in sickle hemoglobin was reported by Ingram (1959). Ingram (1956) had reported that the difference between hemoglobin A and hemoglobin S lies in a single tryptic peptide. His analysis of this peptide, peptide 4, was possible by the methods developed by Sanger for determining the structure of insulin and Edman's stepwise degradation of peptides.

Kan and Dozy (1978) used the HpaI restriction endonuclease polymorphism (actually the linkage principle) to make the prenatal diagnosis of sickle cell anemia (603903). As described in 143020, when 'normal' DNA is digested with HpaI, the beta-globin gene is contained in a fragment 7.6 kilobases long. In persons of African extraction 2 variants were detected, 7.0 kb and 13.0 kb long. These variants resulted from alteration in the normal HpaI recognition site 5000 nucleotides to the 3-prime side of the beta-globin gene. The 7.6 and 7.0 kb fragments were present in persons with Hb A, while 87% of persons with Hb S had the 13.0 kb variant. The method is sufficiently sensitive that the cells in 15 ml of uncultured amniotic fluid sufficed. Restriction enzyme studies indicate that whereas Hb S and Hb C originated against the same genetic background (as independent mutations) and the Hb S in the Mediterranean littoral probably is the same mutation as the West African Hb S, Hb S in Asia is apparently a separate mutation. It does not show association with the noncoding polymorphism (Kan and Dozy, 1979).

Mears et al. (1981) used the linkage of the sickle gene with restriction polymorphisms to trace the origin of the sickle gene in Africa. They found evidence that 2 different chromosomes bearing sickle genes were subjected to selection and expansion in 2 physically close but ethnically separate regions of West Africa, with subsequent diffusion to other areas of Africa. The restriction enzyme MnlI recognizes the sequence G-A-G-G, which also is eliminated by the sickle mutation. The MstII enzyme recognizes the sequence C-C-T-N-A-G-G. Predictably, the resulting fragments are larger than those produced by some other enzymes, and MstII is, therefore, particularly useful in prenatal diagnosis (Wilson et al., 1982). The sickle cell mutation can be identified directly in DNA by use of either of 2 restriction endonucleases, DdeI or MstII (Geever et al., 1981; Kazazian, 1982). The nucleotide substitution alters a specific cleavage site recognized by each of these 2 enzymes. The fifth, sixth, and seventh codons of Hb A are CCT-GAG-GAG; in Hb S, they are CCT-GTG-GAG. The recognition site for DdeI is C-T-N-A-G, in which N = any nucleoside. Chang and Kan (1982) and Orkin et al. (1982) found that the assay using the restriction enzyme MstII is sufficiently sensitive that it can be applied to uncultured amniotic fluid cells. The enzyme DdeI requires that the amniotic cells be cultured to obtain enough DNA for the assay.

Antonarakis et al. (1984) applied the Kazazian haplotype method to the study of the origin of the sickle mutation in Africans. Among 170 beta-S bearing chromosomes, 16 different haplotypes of polymorphic sites were found. The 3 most common beta-S haplotypes, accounting for 151 of the 170, were only rarely seen in chromosomes bearing the beta-A gene in these populations (6 out of 47). They suggested the occurrence of up to 4 independent mutations and/or interallelic gene conversions. By haplotype analysis of the beta-globin gene cluster in cases of Hb S in different parts of Africa, Pagnier et al. (1984) concluded that the sickle mutation arose at least 3 times on separate preexisting chromosomal haplotypes. The Hb S gene is closely linked to 3 different haplotypes of polymorphic endonuclease restriction sites in the beta-like gene cluster: one prevalent in Atlantic West Africa, another in central West Africa, and the last in Bantu-speaking Africa (equatorial, East, and southern Africa). Nagel et al. (1985) found hematologic differences between the first 2 types explicable probably by differences in fetal hemoglobin production. Ramsay and Jenkins (1987) found that 20 of 23 sickle-associated haplotypes in southern-African Bantu-speaking black subjects were the same as those found commonly in the Central African Republic, a finding providing the first convincing biologic evidence for the common ancestry of geographically widely separated speakers of languages belonging to the Bantu family. The 3 haplotypes seen with the beta-S gene in Africa are referred to as Senegal, Benin, and Bantu. The 'Bantu line' extends across the waist of Africa; south of the line, Bantu languages are spoken. Based on their study, Ramsay and Jenkins (1987) suggested that the sickle cell mutation arose only once in the Bantu speakers, presumably in their nuclear area of origin, before the Bantu expansion occurred about 2,000 years ago. In Yaounde, the capital city of Cameroon, Lapoumeroulie et al. (1992) observed a novel RFLP pattern in the study of beta-S chromosomes. This chromosome contained an A-gamma-T gene and the RFLP haplotype was different from all the other beta(S) chromosomes in both the 5-prime and 3-prime regions. All the carriers of this specific chromosome belonged to the Eton ethnic group and originated from the Sanaga river valley.

Kulozik et al. (1986) found that the sickle gene in Saudi Arabia and on the west and east coasts of India exists in a haplotype not found in Africa. They concluded that the data are most consistent with an independent Asian origin of the sickle cell mutation. The distribution of the Asian beta-S-haplotype corresponded to the reported geographic distribution of a mild clinical phenotype of homozygous SS disease. Ragusa et al. (1988) found that the beta-S gene in Sicily is in linkage disequilibrium with the Benin haplotype, the same haplotype observed among sickle cell anemia patients from Central West Africa. In addition, this haplotype is either nonexistent or very rare among nonsickling Sicilian persons. They concluded that the beta-S gene was introduced into Sicily from North Africa and that the gene flow originated in Central West Africa, traveling north through historically well-defined trans-Saharan commercial routes.

Zeng et al. (1994) indicated that 5 different haplotypes associated with Hb S had been described, 4 in Africa (Bantu, Benin, Senegal, and Cameroon) and 1 found in both India and Saudi Arabia (Chebloune et al., 1988). There is a correlation between disease severity and haplotype for at least the 2 extremes of severity: patients with the Indian/Arabian haplotype have the mildest course of disease, while those with the Bantu haplotype exhibit the most severe course. Nucleotide -530 is a binding site for a protein called BP1 (601911), which may be a repressor of the HBB gene. BP1 binds with the highest affinity to the Indian haplotype sequence and with the weakest affinity to the Bantu sequence, which might explain the differences in clinical course in these different population groups. Zeng et al. (1994) demonstrated the same sequence at -530 bp in patients with the Arabian haplotype as in Indian sickle cell anemia patients. This supports the idea of a common origin of the sickle cell mutation in individuals in India and Saudi Arabia.

Sammarco et al. (1988) presented further strong evidence that the Hb S gene in Sicily was brought by North African populations, probably during the Muslim invasions.

Currat et al. (2002) studied the genetic diversity of the beta-globin gene cluster in an ethnically well-defined population, the Mandenka from eastern Senegal. The absence of recent admixture and amalgamation in this population permitted application of population genetics methods to investigate the origin of the sickle cell mutation (Flint et al., 1993) and to estimate its age. The frequency of the sickle cell mutation in the Mandenka was estimated as 11.7%. The mutation was found strictly associated with the single Senegal haplotype. Approximately 600 bp of the upstream region of the beta-globin gene were sequenced for 94 chromosomes, showing the presence of 4 transversions, 5 transitions, and a composite microsatellite polymorphism. The sequence of 22 chromosomes carrying the sickle mutation was also identical to the previously defined Senegal haplotype, suggesting that the mutation is very recent. Maximum likelihood estimates of the age of the mutation using Monte Carlo simulations were 45 to 70 generations (1,350-2,100 years) for different demographic scenarios.

Embury et al. (1987) described a new method for rapid prenatal diagnosis of sickle cell anemia by DNA analysis. The first step involved a 200,000-fold enzymatic amplification of the specific beta-globin DNA sequences suspected of carrying the sickle mutation. Next, a short radiolabelled synthetic DNA sequence homologous to normal beta-A-globin gene sequences is hybridized to the amplified target sequence. The hybrid duplexes are then digested sequentially with 2 restriction endonucleases. The presence of the beta-A or beta-S gene sequence in the amplified target DNA from the patient determines whether the beta-A hybridization probe anneals perfectly or with a single nucleotide mismatch. This difference affects the restriction enzyme digestion of the DNA and the size of the resulting radiolabelled digestion products which can be distinguished by electrophoresis followed by autoradiography. The method was sufficiently sensitive and rapid that same-day prenatal diagnosis using fetal DNA was possible. The same test could be applied to the diagnosis of hemoglobin C disease. Hemoglobin C (Georgetown) also sickles. See Herrick (1910), Sherman (1940), Neel (1949), Pauling et al. (1949), Allison (1954), Ingram (1956, 1957, 1959), Chang and Kan (1981), and Shalev et al. (1988).

Barany (1991) described a new assay designed to detect single base substitutions using a thermostable enzyme similar to the DNA polymerase used in PCR. This enzyme, DNA ligase, specifically links adjacent oligonucleotides only when the nucleotides are perfectly base-paired at the junction. In the presence of a second set of adjacent oligonucleotides, complementary to the first set and the target, the oligonucleotide products may be exponentially amplified by thermal cycling of the ligation reaction. Because a single base mismatch precludes ligation and amplification, it will be easily distinguished. Barany (1991) demonstrated the utility of the method in discriminating between normal and sickle globin genotypes from 10 microliter blood samples.

Prezant and Fischel-Ghodsian (1992) described a trapped-oligonucleotide nucleotide incorporation (TONI) assay for the screening of a mitochondrial polymorphism and also showed that it could distinguish the genotypes of hemoglobins A/C, A/A, A/S, and S/S. The method was considered particularly useful for diagnosing mutations that do not produce alterations detectable by restriction enzyme analysis. It also requires only a single oligonucleotide and no electrophoretic separation of the allele-specific products. It represents an improved and simplified modification of the allele-specific primer extension methods. (TONI, the acronym for the method, is also the given name of the first author.)

Grosveld et al. (1987) identified dominant control region (DCR) sequences that flank the human beta-globin locus and direct high-level, copy-number-dependent expression of the human beta-globin gene in erythroid cells in transgenic mice. By inserting a construct that included 2 human alpha genes and the defective human beta-sickle gene, all driven by the DCR sequences, Greaves et al. (1990) produced 2 mice with relatively high levels of human Hb S in their red cells. Use of this as an animal model for the study of this disease was suggested.

Turhan et al. (2002) presented evidence suggesting that a pathogenetic mechanism in sickle cell vasoocclusion may reside in adherent leukocytes. Using intravital microscopy in mice expressing human sickle hemoglobin, they demonstrated that SS red blood cells bind to adherent leukocytes in inflamed venules, producing vasoocclusion of cremasteric venules. SS mice deficient in P- and E-selectins, which display defective leukocyte recruitment to the vessel wall, were protected from vasoocclusion. Thus, drugs targeting SS RBC-leukocyte or leukocyte-endothelial interactions might prevent or treat the vascular complications of this disease.

Nitric oxide (NO), essential for maintaining vascular tone, is produced from arginine by NO synthase. Plasma arginine levels are low in sickle cell anemia, and Romero et al. (2002) reported that the sickle transgenic mouse model has low plasma arginine. They supplemented these mice with a 4-fold increase in arginine over a period of several months. Mean corpuscular hemoglobin concentration decreased and the percent high-density red cells was reduced. Romero et al. (2002) concluded that the major mechanism by which arginine supplementation reduces red cell density in these mice is by inhibiting the Ca(++)-activated K(+) channel.

In a Jamaican study, Serjeant et al. (1968) described 60 patients with homozygous sickle cell disease who were 30 years of age or older, and Platt et al. (1994) estimated a median survival of 42 to 48 years. Serjeant et al. (2007) stated that the sickle cell clinic at the University of West Indies had treated 102 patients (64.7% women) who survived beyond their 60th birthday. None of the patients received hydroxyurea, and only 2 patients with renal impairment received regular transfusions. The ages of the patients ranged from 60.2 to 85.6 years. Measurement of fetal hemoglobin levels suggested that higher fetal hemoglobin levels probably conferred protection in childhood. The major clinical problems emerging with age were renal impairment and decreased levels of hemoglobin.

Kwiatkowski (2005) noted that HbS homozygotes have sickle-cell disease, whereas heterozygosity confers a 10-fold increase in protection from life-threatening malaria (611162) and lesser protection against mild malaria.

Cholera et al. (2008) found that P. falciparum (Pf)-infected HbA/HbS erythrocytes did not bind to microvascular endothelial cells as well as Pf-infected HbA/HbA erythrocytes. Reduced binding correlated with altered display of the major Pf cytoadherence ligand on erythrocyte membranes. Cholera et al. (2008) noted that this protective mechanism had features in common with that of HbC (141900.0038), and they suggested that weakening of cytoadherence interactions may influence the degree of malaria protection in HbA/HbS children.

Modiano et al. (2008) adopted 2 partially independent haplotypic approaches to study the Mossi population in Burkina Faso, where both the HbS and HbC alleles are common. They showed that both alleles are monophyletic, but that the HbC allele has acquired higher recombinatorial and DNA slippage haplotypic variability or linkage disequilibrium decay and is likely older than HbS. Modiano et al. (2008) inferred that the HbC allele has accumulated mainly through recessive rather than a semidominant mechanism of selection.

Gouagna et al. (2010) used cross-sectional surveys of 3,739 human subjects and transmission experiments involving 60 children and over 6,000 mosquitoes in Burkina Faso, West Africa, to test whether the HBB variants HbC and HbS, which are protective against malaria, are associated with transmission of the parasite from the human host to the Anopheles mosquito vector. They found that HbC and HbS were associated with significant 2-fold in vivo (P = 1.0 x 10(-6)) and 4-fold ex vivo (P = 7.0 x 10(-5)) increases of parasite transmission from host to vector. In addition, mean oocyte densities were particularly high in mosquitoes fed from HbS carriers.

Ferreira et al. (2011) demonstrated that wildtype mice or mice expressing normal human Hb, but not mice expressing Hbs, developed experimental cerebral malaria (ECM) 6 to 12 days after infection with the murine malaria parasite, Plasmodium berghei. The Hbs mice eventually succumbed to the unrelated condition of hyperparasitemia-induced anemia. Tolerance to Plasmodium infection was associated with high levels of Hmox1 (141250) expression in hematopoietic cells, and mice expressing Hbs became susceptible to ECM when Hmox1 expression was inhibited. Hbs induced expression of Hmox1 in an Nrf2 (NFE2L2; 600492)-dependent manner, which inhibited the production of chemokines and Cd8-positive T cells associated with ECM pathogenesis. Ferreira et al. (2011) concluded that sickle hemoglobin suppresses the onset of ECM via induction of HMOX1 and the production of carbon monoxide, which inhibits the accumulation of free heme, affording tolerance to Plasmodium infection.

Cyrklaff et al. (2011) found that HbS and HbC affect the trafficking system that directs parasite-encoded proteins to the surface of infected erythrocytes. Cryoelectron tomography revealed that P. falciparum generates a host-derived actin cytoskeleton within the cytoplasm of wildtype red blood cells that connects the Maurer clefts with the host cell membrane and to which transport vesicles are attached. The actin cytoskeleton and the Maurer clefts were aberrant in erythrocytes containing HbS or HbC. Hemoglobin oxidation products, enriched in HbS and HbC erythrocytes, inhibited actin polymerization in vitro and may account for the protective role in malaria.


.0244   HEMOGLOBIN S (ANTILLES)

HBB, GLU6VAL AND VAL23ILE
SNP: rs334, rs33929459, gnomAD: rs334, rs33929459, ClinVar: RCV000016286, RCV000016573, RCV000016574, RCV000016575, RCV000016576, RCV000016577, RCV000016579, RCV000016580, RCV000016877, RCV000016879, RCV000030905, RCV000224000, RCV000477892, RCV000576548, RCV000623118, RCV000723337, RCV000736024, RCV001192494, RCV001255121, RCV001535873, RCV001824571, RCV002251908, RCV002288496, RCV003150808, RCV003407340

This variant has electrophoretic mobility in standard conditions identical to that of Hb S but shows a slightly higher pI than Hb S on isoelectric focusing. Heterozygous carriers of this variant hemoglobin exhibit sickling disorders. This observation may provide a clue to the unexplained clinical sickling disorders in some A/S carriers, in whom careful biochemical analyses may reveal other examples of double mutations in the beta chain. See Monplaisir et al. (1986). Pagnier et al. (1990) introduced the val23-to-ile mutation into beta-globin cDNA by site-directed mutagenesis. The beta-globin chain was synthesized using an expression vector and hemoglobin tetramers were reconstituted. When mixed with equal amounts of hemoglobin S, facilitation of polymerization was observed. Pagnier et al. (1990) listed 5 other hemoglobin variants which contain both the sickle mutation and a second amino acid substitution in the same beta chain.

Popp et al. (1997) bred 2 homozygous viable Hb S Antilles transgene insertions into a strain of mice that produce hemoglobins with a higher affinity for oxygen than normal mouse Hb. The rationale was that the high oxygen affinity hemoglobin, the lower oxygen affinity of Hb S Antilles, and the lower solubility of deoxygenated Hb Antilles than Hb S would favor deoxygenation and polymerization of human Hb S Antilles in the red cells of the high oxygen affinity mice. The investigators found that the mice produced a high and balanced expression of human alpha and human beta (S Antilles) globins, that 25 to 35% of their RBCs were misshapen in vivo, and that in vitro deoxygenation of their blood induced 30 to 50% of the RBCs to form classic elongated sickle cells with pointed ends. The mice exhibited reticulocytosis, an elevated white blood cell count, and lung and kidney pathology commonly found in sickle cell patients, which should make these mice useful for experimental studies on possible therapeutic intervention of sickle cell disease.


.0245   HEMOGLOBIN S (OMAN)

HEMOGLOBIN S/O (ARAB)
HBB, GLU6VAL AND GLU121LYS
SNP: rs334, rs33946267, gnomAD: rs334, rs33946267, ClinVar: RCV000016286, RCV000016524, RCV000016525, RCV000016573, RCV000016574, RCV000016575, RCV000016576, RCV000016577, RCV000016579, RCV000016580, RCV000016863, RCV000016877, RCV000016879, RCV000029993, RCV000030905, RCV000202511, RCV000224000, RCV000477892, RCV000508438, RCV000576548, RCV000587075, RCV000623118, RCV000723337, RCV001192494, RCV001255121, RCV001535873, RCV001824571, RCV002251908, RCV002288496, RCV002476974, RCV003150808, RCV003407340

Langdown et al. (1989) described a doubly substituted sickling hemoglobin with the change of glu-to-val at beta 6 (141900.0243) and glu-to-lys at beta 121 (141900.0202). The double substitution resulted in a variant with reduced solubility and apparent increase in red cell sickling tendency. Hemoglobin S (Oman) combines the classic Hb S mutation (glu6 to val), with the Hb O (Arab) mutation (glu121 to lys). Nagel et al. (1998) studied a pedigree of heterozygous carriers of Hb S (Oman) that segregated into 2 types of patients: those expressing about 20% Hb S (Oman) and concomitant -alpha/alpha-alpha thalassemia and those with about 14% of Hb S (Oman) and concomitant -alpha/-alpha thalassemia. The higher expressors of Hb S (Oman) had a sickle cell anemia clinical syndrome of moderate intensity, whereas the lower expressors had no clinical syndrome and were comparable to the solitary case first described in Oman. In addition, the higher expressors exhibited a unique form of irreversibly sickled cell reminiscent of a 'yarn and knitting needle' shape, in addition to folded and target cells. Purified Hb S (Oman) has a C(SAT) (solubility of the deoxy polymer) of 11 g/dL, much lower than Hb S alone (17.8 g/dL). Another double mutant, Hb S (Antilles) (141900.0244), has a similarly low C(SAT) and much higher expression (40 to 50%) in the trait form, but has a phenotype that is similar in intensity to the trait form of Hb S (Oman). Nagel et al. (1998) concluded that the pathology of heterozygous S (Oman) is the product of recipient properties of the classic mutation which are enhanced by the second mutation at beta-121. In addition, the syndrome is further enhanced by a hemolytic anemia induced by the beta-121 mutation. They speculated that the hemolytic anemia results from the abnormal association of the highly positively charged Hb S (Oman) (3 charges different from normal hemoglobin) with the RBC membrane.

To characterize better the clinical and laboratory aspects of Hb S (Oman), also called Hb S/O (Arab), Zimmerman et al. (1999) reviewed the Duke University Medical Center experience. They identified 13 African American children and adults with Hb S/O (Arab), ranging in age from 2.7 to 62.5 years. All patients had hemolytic anemia with a median hemoglobin of 8.7 gm/dL and a median reticulocyte count of 5.8%. The peripheral blood smear typically showed sickled erythrocytes, target cells, polychromasia, and nucleated red blood cells. All 13 patients had had significant clinical sickling events, including acute chest syndrome (11), recurrent vasoocclusive painful events (10), dactylitis (7), gallstones (5), nephropathy (4), aplastic crises (2), avascular necrosis (2), leg ulcers (2), cerebrovascular accident (1), osteomyelitis (1), and retinopathy (1). Death had occurred in 4 patients, including 2 from pneumococcal sepsis/meningitis at ages 5 and 10 years, 1 of acute chest syndrome at age 14 years, and 1 of multiorgan failure at age 35 years. Zimmerman et al. (1999) concluded that Hb S/O (Arab) disease is a severe sickling hemoglobinopathy with laboratory and clinical manifestations similar to those of homozygous sickle cell anemia.


.0246   HEMOGLOBIN S (PROVIDENCE)

HBB, GLU6VAL AND LYS82ASX
SNP: rs334, rs33991993, gnomAD: rs334, rs33991993, ClinVar: RCV000016286, RCV000016559, RCV000016573, RCV000016574, RCV000016575, RCV000016576, RCV000016577, RCV000016579, RCV000016580, RCV000016877, RCV000016879, RCV000030905, RCV000224000, RCV000477892, RCV000576548, RCV000623118, RCV000641585, RCV000723337, RCV001192494, RCV001255121, RCV001535873, RCV001824571, RCV002251908, RCV002288496, RCV003150808, RCV003407340

Gale et al. (1988) described a hemoglobin carrying 2 substitutions, the standard substitution of Hb S (beta6 glu-to-val) and the substitution of Hb Providence (beta82 lys-to-asx). (There is partial postsynthetic deamination of asparagine to aspartic acid.) The double mutation is electrophoretically silent; if hemoglobin electrophoresis alone were done, the abnormality would be missed.


.0247   HEMOGLOBIN S (TRAVIS)

HBB, GLU6VAL AND ALA142VAL
SNP: rs334, rs33921821, gnomAD: rs334, ClinVar: RCV000016286, RCV000016573, RCV000016574, RCV000016575, RCV000016576, RCV000016577, RCV000016579, RCV000016580, RCV000016877, RCV000016879, RCV000030905, RCV000224000, RCV000477892, RCV000576548, RCV000623118, RCV000723337, RCV001192494, RCV001255121, RCV001535873, RCV001824571, RCV002251908, RCV002288496, RCV003150808, RCV003407340

See Moo-Penn et al. (1977).


.0248   HEMOGLOBIN SABINE

HBB, LEU91PRO
SNP: rs33917785, ClinVar: RCV000016581, RCV000508375

The hemoglobin is unstable, causing hemolytic anemia in the heterozygote. See Schneider et al. (1969) and Bogoevski et al. (1983). Hull et al. (1998) reported 2 cases of Hb Sabine, in a mother in whom the mutation had apparently arisen de novo and her son. They stated that more than 100 unstable hemoglobins causing hemolytic anemia had been described. Less than 20% of the unstable hemoglobins that have been characterized affect the alpha-globin chain.


.0249   HEMOGLOBIN SAINT JACQUES

ERYTHROCYTOSIS 6, INCLUDED
HBB, ALA140THR
SNP: rs34980264, ClinVar: RCV000016582, RCV000641604

Produces erythrocytosis by alteration of the site of fixation of 2,3-diphosphoglycerate (Rochette et al., 1984).


.0250   HEMOGLOBIN SAITAMA

HBB, HIS117PRO
SNP: rs33935673, rs33978082, gnomAD: rs33978082, ClinVar: RCV000016583

See Ohba et al. (1983).


.0251   HEMOGLOBIN SAKI

HBB, LEU14PRO
SNP: rs33935445, ClinVar: RCV000016584, RCV000508682, RCV001527030, RCV001826467, RCV002490377

See Beuzard et al. (1975) and Milner et al. (1976).


.0252   HEMOGLOBIN SAN DIEGO

ERYTHROCYTOSIS 6, INCLUDED
HBB, VAL109MET
SNP: rs121909812, rs33969677, ClinVar: RCV000016585, RCV000169614, RCV000641606, RCV001553627, RCV003476897

This hemoglobin is characterized by high oxygen affinity, and erythrocytosis is associated. See Anderson (1974), Nute et al. (1974), and Harkness et al. (1981). Williamson et al. (1995) observed a 30-year-old man of West Indian origin who showed compound heterozygosity for Hb San Diego and Hb S (141900.0243). He had suffered for about 6 months from severe colicky abdominal pain in episodes of several hours duration. He showed erythrocytosis with a hemoglobin value of 18.8 g/dl. The Hb San Diego mutation represented a GTG-to-ATG change. The Hb S mutation was inherited from the mother; Williamson et al. (1995) suggested that the Hb San Diego mutation occurred de novo on the chromosome 11 derived from the father. DNA testing was consistent with the assumed paternity. The Hb San Diego mutation occurred at a CpG dinucleotide. It was concluded that the abdominal pain was due to increased blood viscosity and the symptoms were relieved by venesection.


.0253   HEMOGLOBIN SANTA ANA

HBB, LEU88PRO
SNP: rs33940204, ClinVar: RCV000016586, RCV000757364, RCV003137530

See Opfell et al. (1968) and Tanaka et al. (1985).


.0254   HEMOGLOBIN SAVANNAH

HBB, GLY24VAL
SNP: rs33968721, ClinVar: RCV000016587

See Huisman et al. (1971).


.0255   HEMOGLOBIN SAVERNE

HBB, 1-BP DEL, HIS143PRO, FS
SNP: rs63749858, gnomAD: rs63749858, ClinVar: RCV000016588

Probable frameshift mutation resulting from deletion of the second base of the triplet coding for beta his 143; CAC becomes CCA (PRO). The last part of the beta gene code, 143rd residue on, becomes CAC-AGT-ATC-ACT-AAG-CTC-GCT-TTC-TTG-CTG-TCC-AAT-TTC-TAT-TAA, which reads pro-ser-ile-thr-lys-leu-ala-phe-leu-leu-ser-asn-phe-tyr-stop (COOH). Thus, the beta chain is 156 amino acids long rather than 146. See Delanoe et al. (1984).


.0256   HEMOGLOBIN SEATTLE

HBB, ALA70ASP
SNP: rs33946401, ClinVar: RCV000016589

Hemoglobin Seattle was discovered by Stamatoyannopoulos et al. (1969), who showed that it is associated with a considerable decrease in oxygen affinity with almost normal heme-heme interaction and normal Bohr effect. It was their conclusion and that of Huehns et al. (1970) that the change was ala76-to-glu. However, studies reported by Kurachi et al. (1973) led to the conclusion that Hb Seattle has a substitution of alanine by aspartic acid at position 70 of the beta polypeptide. Chow et al. (1994) reported a second example of Hb Seattle in a Ukrainian family.


.0257   HEMOGLOBIN SENDAGI

HEMOGLOBIN WARSAW
HBB, PHE42VAL
SNP: rs33924146, ClinVar: RCV000016590

Ogata et al. (1986) and Honig et al. (1990) studied this unstable variant, which has low oxygen affinity and an increased susceptibility to methemoglobin formation.


.0258   HEMOGLOBIN SHANGHAI

HBB, GLN131PRO
SNP: rs33950778, ClinVar: RCV000016592

The proband had chronic hemolytic anemia aggravated by oxidated drugs and common colds. Her 10-year-old son was also affected. Biosynthesis studies indicated a normal rate of synthesis, but relatively fast degradation of the mutant beta chain (Zeng et al., 1987).


.0259   HEMOGLOBIN SHELBY

HEMOGLOBIN LESLIE
HEMOGLOBIN DEACONESS
HBB, GLN131LYS
SNP: rs33910209, ClinVar: RCV000016593, RCV000016594, RCV000016595, RCV000759798, RCV001001860

See Felice et al. (1978), Carcassi et al. (1980), and Moo-Penn et al. (1984). Deletion of glutamine at beta 131 in Hb Leslie was reported by Lutcher et al. (1976) and the same deletion was reported in Hb Deaconess by Moo-Penn et al. (1975). Later, Moo-Penn et al. (1984) showed that Hb Deaconess and Hb Leslie are identical to Hb Shelby. All three have substitution of lysine for glutamine at beta 131. Adachi et al. (1993) described a compound heterozygote for Hb S and Hb Shelby. Hb Shelby, like Hb A, can form hybrids with Hb S which participate in polymer formation in vitro. However, Hb S/Hb Shelby hybrids copolymerize with Hb S less than Hb A/S hybrids. The mild clinical presentation of the patient was attributed to this fact.


.0260   HEMOGLOBIN SHEPHERDS BUSH

HBB, GLY74ASP
SNP: rs33976006, ClinVar: RCV000016596

See White et al. (1970) and Sansone et al. (1977).


.0261   HEMOGLOBIN SHERWOOD FOREST

HBB, ARG104THR
SNP: rs33911434, ClinVar: RCV000016597, RCV000507183

See Ryrie et al. (1977).

Williamson et al. (1994) described a 22-year-old Pakistani male with polycythemia associated with homozygosity for this high-affinity hemoglobin mutant. Whereas 2 previously reported persons with the mutant hemoglobin were heterozygotes and were hematologically normal, the homozygous state was associated with compensatory erythrocytosis resulting from decreased delivery of oxygen to the tissues. Both parents and both sibs were heterozygous for the hemoglobin mutant and were hematologically normal. This may have been the first example of a beta-globin mutation producing polycythemia in homozygotes, but not in heterozygotes.


.0262   HEMOGLOBIN SHOWA-YAKUSHIJI

BETA-PLUS-THALASSEMIA
BETA-SHOWA-YAKUSHIJI THALASSEMIA
HBB, LEU110PRO
SNP: rs35256489, gnomAD: rs35256489, ClinVar: RCV000016598, RCV000016599, RCV000016600, RCV000589517, RCV001004561, RCV002476975

In a Japanese family, Kobayashi et al. (1987) and Naritomi et al. (1988) described a novel HBB mutation that produced the beta-thalassemia phenotype (613985) through a posttranslational mechanism. Substitution of proline for leucine at position 110 greatly reduced the molecular stability of the beta-globin subunit, leading to total destruction of the variant globin chains by proteolysis. The mutation could be identified after digestion with the restriction enzyme MspI. They named the variant Hb Showa-Yakushiji, after the 2 districts where the probands resided. Other variant hemoglobins that are very unstable and lead to thalassemia include Hb Indianapolis (141900.0117) and Hb Quong Sze (141900.0005).

In 4 unrelated individuals in India, Edison et al. (2005) found the hyper-unstable variant Hb Showa-Yakushiji in compound heterozygosity with other mutations producing beta-thalassemia or with Hb E (141900.0071). In all 4 patients, the mutation was found on the same haplotype, which differed from the Japanese haplotype, indicating its independent origin in India.


.0263   HEMOGLOBIN SIRIRAJ

HEMOGLOBIN G (HONAN)
HBB, GLU7LYS
SNP: rs34948328, ClinVar: RCV000016602, RCV001800303

This HBB gene variant was discovered in a Thai family by Tuchinda et al. (1965) and was subsequently identified in several Chinese by Blackwell et al. (1972). Chang et al. (1999) observed the same variant in a Taiwanese family. DNA analysis detected a G-to-A transition at the first base of codon 7 (GAG to AAG). This mutation creates an MboII site that is highly specific for Hb Siriraj.


.0264   HEMOGLOBIN SOGN

HBB, LEU14ARG
SNP: rs33935445, ClinVar: RCV000016604, RCV000588440, RCV001272129

Hb Sogn was first described in Norway by Monn et al. (1968). Fairbanks et al. (1990) described the first known instances of Hb Sogn outside of Norway, in 2 families, both of Norwegian descent. Hb Sogn has been described in Norwegian families and in American families from the upper midwest where settlement of Scandinavian families was common. Miller et al. (1996) described the hemoglobin variant in a family residing in Illinois; the proband's maternal grandfather was Norwegian. Codon 14 showed a CTG (leu)-to-CGG (arg) change. The proband married a person who was homozygous for alpha-thalassemia-2. The couple had 2 daughters who offered the opportunity of comparing data between Hb Sogn heterozygotes with 4 alpha-globin genes and 3 alpha-globin genes. Mild microcytosis and hypochromia in the father was due to the presence of alpha-thal-2 homozygosity and that in the mother to the presence of the mildly unstable Hb Sogn. Striking microcytosis and hypochromia in 1 daughter could be attributed to the combination of a the alpha-thal-2 trait and Hb Sogn heterozygosity.


.0265   HEMOGLOBIN SOUTHAMPTON

HEMOGLOBIN CASPER
HBB, LEU106PRO
SNP: rs33941844, ClinVar: RCV000016605, RCV000016606

See Hyde et al. (1972), Jones et al. (1973), and Koler et al. (1973), who described Hb Southampton (Casper) as a leu106-to-pro substitution in the HBB gene.

Nusapan and Conant (2023) noted that Hb Southampton (Casper) is a rare unstable hemoglobinopathy caused by a c.320T-C transition in the HBB gene, resulting in a leu107-to-pro (L107P) substitution. The mutation results in distortion of the tertiary structure of the hemoglobin molecule, leading to membrane damage and RBC destruction. Hepatosplenomegaly, chronic hemolytic anemia, and methemoglobinemia are common features. Macrocytosis is sometimes observed.


.0266   HEMOGLOBIN SOUTH FLORIDA

HBB, NH2 EXTENSION, VAL1MET, METi RETAINED
SNP: rs33958358, gnomAD: rs33958358, ClinVar: RCV000016609, RCV000508674, RCV001831572

The initiator methionine residue (METi) is preserved. This variant was first discovered in a patient who appeared to have markedly elevated Hb A(1c) as estimated by ion exchange chromatography. Glycosylated hemoglobin measured by a colorimetric method with thiobarbituric acid was normal, however. If it were not for the fact that methionine is 1 of the 4 N-terminal amino acids (alanine, glycine, serine, methionine) that participate in acetylation, this abnormal amino acid substitution would have gone unrecognized. Acetylation of the N-terminal methionine residue occurs less easily than in other amino acids; thus, hemoglobin South Florida could not be recognized by hemoglobin electrophoresis. In contrast, acetylation of alanine in hemoglobin Raleigh is 100% and that variant can be recognized by hemoglobin electrophoresis. See Boissel et al. (1985) and Shah et al. (1986). Malone et al. (1987) reported a family study. The fundamental change is not in the codon for the initiator mutation but in the codon for the first residue for the mature beta-globin chain, valine, which is converted to methionine. Because the initiator methionine is retained, this methionine is substituted for valine as residue 2 in the mature chain of Hb South Florida.


.0267   HEMOGLOBIN ST. ANTOINE

HBB, GLY74DEL AND LEU75DEL
SNP: rs63750968, ClinVar: RCV000016610

Two amino acids, glycine and leucine, are deleted from beta 74 and 75. See Wajcman et al. (1973).


.0268   HEMOGLOBIN ST. LOUIS

HEINZ BODY HEMOLYTIC ANEMIA
HBB, LEU28GLN
SNP: rs33916412, ClinVar: RCV000016611, RCV000016612

This is a form of Hb M, differing from other Hb M variants by the fact that the substitution is not for the histidine at E7 or F8. Hb M (Milwaukee) is another. Severe Heinz body anemia, in addition to methemoglobinemia, is associated with Hb St. Louis. The beta heme group is permanently in a ferric state. See Cohen-Solal et al. (1974), Anderson (1976), Thillet et al. (1976), and Wiedermann et al. (1986).


.0269   HEMOGLOBIN ST. MANDE

HBB, ASN102TYR
SNP: rs33927739, ClinVar: RCV000016603

This hemoglobin variant has a low oxygen affinity, resulting in cyanosis. See Arous et al. (1981). Poyart et al. (1990) found that the functional properties of St. Mande are intermediary between those of normal Hb A and Hb Kansas (0.0145).


.0270   HEMOGLOBIN STANMORE

HBB, VAL111ALA
SNP: rs35871407, ClinVar: RCV000016607

See Como et al. (1984).


.0271   HEMOGLOBIN STRASBOURG

HBB, VAL23ASP
SNP: rs33945546, ClinVar: RCV000016608, RCV000985755

Hb Strasbourg was first observed in a female from northern Portugal and in 1 of her 2 children. Garel et al. (1976) incorrectly thought that the valine at position 20 was substituted. See Forget (1977). Bisse et al. (1998) provided information on a German family with the same abnormality. This was the second observation of this hemoglobin variant. The 23-year-old propositus had a hemoglobin level of 19.8 g/dl. The variant was shown to have a high oxygen affinity. Codon 23 of the HBB gene was changed from GTT (val) to GAT (asp).


.0272   HEMOGLOBIN SUMMER HILL

HBB, ASP52HIS
SNP: rs33961886, gnomAD: rs33961886, ClinVar: RCV000016613, RCV000506716, RCV001284630, RCV001826468

No hematologic abnormality. See Wilkinson et al. (1980) and Cin et al. (1983).


.0273   HEMOGLOBIN SUNNYBROOK

HBB, PRO36ARG
SNP: rs33993004, ClinVar: RCV000016614

See Ali et al. (1988).


.0274   HEMOGLOBIN SYDNEY

HBB, VAL67ALA
SNP: rs33918343, ClinVar: RCV000016615

Like hemoglobins Koln and Genova, this hemoglobin has no electrophoretic abnormality but is unstable, forming intracellular precipitates. See Carrell et al. (1967) and Casey et al. (1978).


.0275   HEMOGLOBIN SYRACUSE

ERYTHROCYTOSIS 6, INCLUDED
HBB, HIS143PRO
SNP: rs121909805, rs33918338, gnomAD: rs33918338, ClinVar: RCV000016616, RCV000641613, RCV001001407

See Jensen et al. (1975).


.0276   HEMOGLOBIN T (CAMBODIA)

HBB, GLU26LYS AND GLU121GLN
SNP: rs33946267, rs33950507, gnomAD: rs33946267, rs33950507, ClinVar: RCV000016317, RCV000016329, RCV000016330, RCV000016331, RCV000016332, RCV000016617, RCV000016758, RCV000016858, RCV000029994, RCV000202465, RCV000202534, RCV000496072, RCV000506024, RCV000521111, RCV000723826, RCV000778329, RCV000778330, RCV000853358, RCV001175348, RCV001536065, RCV002247348, RCV002288495, RCV002415419, RCV003415712

See Barwick et al. (1985). Combines substitutions of Hb E and Hb O (Arab): substitution of lysine for glutamic acid at beta 26 and of glutamine for glutamic acid at beta 121.


.0277   HEMOGLOBIN TA-LI

HBB, GLY83CYS
SNP: rs33930385, gnomAD: rs33930385, ClinVar: RCV000016618, RCV000985740

See Blackwell et al. (1971).


.0278   HEMOGLOBIN TACOMA

HEINZ BODY HEMOLYTIC ANEMIA
HBB, ARG30SER
SNP: rs1135071, gnomAD: rs1135071, ClinVar: RCV000016619, RCV000016620, RCV000985758, RCV001831573, RCV002288497

See Baur and Motulsky (1965), Brimhall et al. (1969), Idelson et al. (1974), Deacon-Smith and Lee-Potter (1978), and Harano et al. (1985).


.0279   HEMOGLOBIN TAK

HBB, +8 RESIDUES
SNP: rs33999427, ClinVar: RCV000016621, RCV000506874, RCV001375559, RCV003313962

The usual terminal dipeptide 145-146 of the beta chain is lacking and is replaced by 10 residues attached to the C-terminal end. Hemoglobin Constant Spring is a termination defect of the alpha chain. See Flatz et al. (1971). Characterized on the basis of amino acid analysis, this variant was assumed to be due to an insertion of the dinucleotide CA into codon 146, CAC-to-CA(CA)C, which abolished the normal stop codon at position 147 and caused a frameshift with elongation of the beta chain by 11 amino acids. The variant had previously been described in a few Thai families. Hoyer et al. (1998) reported the DNA sequence of Hb Tak in an individual of Cambodian descent who was a Hb E/Tak compound heterozygote. In contrast with extended variants of the alpha-globin gene that are expressed as alpha-thalassemias, the hematologic effect of Hb Tak/Hb E was a mild polycythemia. The combination of Hb Tak/Hb E was not expressed as a thalassemia.

Shih et al. (2005) reported heterozygosity for Hb Tak in a Taiwanese individual.


.0280   HEMOGLOBIN TAKAMATSU

HBB, LYS120GLN
SNP: rs33924134, ClinVar: RCV000016622

See Iuchi et al. (1980) and Kawata et al. (1989).


.0281   HEMOGLOBIN TAMPA

HBB, ASP79TYR
SNP: rs33990858, ClinVar: RCV000016623, RCV001811164

See Johnson et al. (1980).


.0282   HEMOGLOBIN TIANSHUI

HBB, GLN39ARG
SNP: rs35973315, ClinVar: RCV000016624

In a healthy 34-year-old Chinese male of Han nationality, Li et al. (1990) identified a hemoglobin variant and showed that it had a replacement of glutamine by arginine at residue 39.


.0283   HEMOGLOBIN TILBURG

HBB, ASP73GLY
SNP: rs33967755, ClinVar: RCV000016625

This hemoglobin and 3 others with a single amino acid substitution at the same site have reduction in affinity for oxygen. See Bernini and Giordano (1988).


.0284   HEMOGLOBIN TOCHIGI

HBB, GLY56DEL, ASN57DEL, PRO58DEL, LYS59DEL
SNP: rs63751103, ClinVar: RCV000016626

Deletion of residues 56-59 of the beta chain. See Shibata et al. (1970).


.0285   HEMOGLOBIN TOURS

HBB, THR87DEL
SNP: rs63751171, ClinVar: RCV000016627

See Wajcman et al. (1973).


.0286   HEMOGLOBIN TOYOAKE

HBB, ALA142PRO
SNP: rs33931806, ClinVar: RCV000016628

See Hirano et al. (1981) and Imai et al. (1981).


.0287   HEMOGLOBIN TUBINGEN

HBB, LEU106GLN
SNP: rs33941844, ClinVar: RCV000016630

See Kohne et al. (1976). Philippe et al. (1993) described this hemoglobin variant, a cause of methemoglobinemia, in a 53-year-old Belgian woman. Her father had been cyanotic throughout his life. This was the second report of this hemoglobin variant.


.0288   HEMOGLOBIN TUNIS

HBB, PRO124SER
SNP: rs35461710, ClinVar: RCV000016631

See Mrad et al. (1988).


.0289   HEMOGLOBIN TY GARD

ERYTHROCYTOSIS 6, INCLUDED
HBB, PRO124GLN
SNP: rs33983276, ClinVar: RCV000016632, RCV000641615, RCV000759072

See Bursaux et al. (1978).


.0290   HEMOGLOBIN VAASA

HBB, GLN39GLU
SNP: rs11549407, gnomAD: rs11549407, ClinVar: RCV000016633

See Kendall et al. (1977).


.0291   HEMOGLOBIN VANCOUVER

HBB, ASP73TYR
SNP: rs33945705, gnomAD: rs33945705, ClinVar: RCV000016634

See Jones et al. (1976).


.0292   HEMOGLOBIN VANDERBILT

ERYTHROCYTOSIS 6, INCLUDED
HBB, SER89ARG
SNP: rs35351128, ClinVar: RCV000016635, RCV000641619

See Puett et al. (1977) and Paniker et al. (1978).


.0293   HEMOGLOBIN VICKSBURG

HBB, LEU75DEL
SNP: rs35452098, ClinVar: RCV000016636

See Adams et al. (1981). When they failed to find evidence of deletion of leu75 in genomic DNA, Coleman et al. (1988) proposed somatic mutation. A more plausible explanation, perhaps, is one parallel to that obtaining in the case of Hb Atlanta-Coventry (141900.0013).


.0294   HEMOGLOBIN VILLEJUIF

HBB, THR123ILE
SNP: rs33935383, gnomAD: rs33935383, ClinVar: RCV000016637, RCV000506551, RCV001277082, RCV003476898

This mutation was discovered as a silent and asymptomatic variant in an 87-year-old French woman who coincidentally had polycythemia vera (Wajcman et al., 1989).. Carbone et al. (2001) reported the second observation of this hemoglobin variant in 3 related subjects from Montesarchio in southern Italy. The DNA change was ACC to ATC.


.0295   HEMOGLOBIN VOLGA

HEMOGLOBIN DRENTHE
HBB, ALA27ASP
SNP: rs33954632, gnomAD: rs33954632, ClinVar: RCV000016638, RCV000016639, RCV001800304

See Kuis-Reerink et al. (1976), Ockelford et al. (1980), Sciarratta et al. (1985), and Falcioni et al. (1988). Blanke et al. (1989) reported a possible de novo mutation in a Dane.


.0296   HEMOGLOBIN WARWICKSHIRE

HBB, PRO5ARG
SNP: rs34769005, ClinVar: RCV000016640

See Wilson et al. (1984).


.0297   HEMOGLOBIN WIEN

HBB, TYR130ASP
SNP: rs35834416, ClinVar: RCV000016641

See Perutz and Lehmann (1968) and Lorkin et al. (1974).


.0298   HEMOGLOBIN WILLAMETTE

HBB, PRO51ARG
SNP: rs33969727, ClinVar: RCV000016629

See Jones et al. (1976-77), Quarum et al. (1983), and Martinez and Canizares (1984).


.0299   HEMOGLOBIN WINDSOR

HBB, VAL11ASP
SNP: rs35140348, ClinVar: RCV000016642

Gilbert et al. (1989) found this variant in a 9-month-old child who presented with hemolytic anemia in association with intercurrent viral infection. Instability of the hemoglobin molecule as well as increase in oxygen affinity was demonstrated.


.0300   HEMOGLOBIN WOOD

ERYTHROCYTOSIS 6, INCLUDED
HBB, HIS97LEU
SNP: rs33951978, ClinVar: RCV000016643, RCV000641622

See Taketa et al. (1975).


.0301   HEMOGLOBIN YAKIMA

ERYTHROCYTOSIS 6, INCLUDED
HBB, ASP99HIS
SNP: rs33954595, ClinVar: RCV000016644, RCV000641624

Polycythemia occurs with this hemoglobinopathy as with hemoglobin Chesapeake. See Jones et al. (1967), Novy et al. (1967), and Osgood et al. (1967).


.0302   HEMOGLOBIN YAMAGATA

HBB, LYS132ASN
SNP: rs33946775, ClinVar: RCV000016645

See Harano et al. (1990).

Hemoglobin Yamagata as reported by Harano et al. (1990) was caused by a change of codon 132 in the HBB gene from AAA (lys) to AAC (asn). Han et al. (1996) found the same amino acid substitution in a 37-year-old Korean woman to be caused by a change of codon 132 from AAA to AAT. No distinctive clinical abnormalities were detected.


.0303   HEMOGLOBIN YATSUSHIRO

HBB, VAL60LEU
SNP: rs33990253, ClinVar: RCV000016646

See Kagimoto et al. (1978).


.0304   HEMOGLOBIN YOKOHAMA

HBB, LEU31PRO
SNP: rs33920173, ClinVar: RCV000016647

See Nakatsuji et al. (1981). Plaseska et al. (1991) described a de novo mutation in a Yugoslavian boy with severe transfusion-dependent hemolytic anemia. The patients of Nakatsuji et al. (1981) were a 33-year-old Japanese woman with chronic hemolytic anemia and her son with milder symptoms.


.0305   HEMOGLOBIN YORK

ERYTHROCYTOSIS 6, INCLUDED
HBB, HIS146PRO
SNP: rs33954264, ClinVar: RCV000016648, RCV000641629

See Bare et al. (1976) and Kosugi et al. (1983).


.0306   HEMOGLOBIN YOSHIZUKA

HBB, ASN108ASP
SNP: rs33958637, ClinVar: RCV000016649

Reduced oxygen affinity like hemoglobin Kansas. See Imamura et al. (1969).


.0307   HEMOGLOBIN YPSILANTI

ERYTHROCYTOSIS 6, INCLUDED
HBB, ASP99TYR
SNP: rs33954595, ClinVar: RCV000016650, RCV000641630

Substitution in beta chain results in increased oxygen affinity leading to erythremia and abnormal polymerization manifested in heterozygotes by hybrid hemoglobin molecules containing both the Ypsi beta chain and the normal beta chain. See Glynn et al. (1968).


.0308   HEMOGLOBIN YUKUHASHI

HEMOGLOBIN DHOFAR
HBB, PRO58ARG
SNP: rs33991472, ClinVar: RCV000016651, RCV000030905, RCV002222352

See Yanase et al. (1968) and Marengo-Rowe et al. (1968).


.0309   HEMOGLOBIN YUSA

HBB, ASP21TYR
SNP: rs33950093, ClinVar: RCV000016653, RCV000759802

See Harano et al. (1981) and Ohba et al. (1990).


.0310   HEMOGLOBIN ZURICH

HBB, HIS63ARG
SNP: rs33985544, ClinVar: RCV000016654, RCV001284634

Drug-induced hemolysis results from this variant hemoglobin. The affinity of Hb Zurich for carbon monoxide is about 65 times that observed in normal hemoglobin A. Carboxyhemoglobin content in persons with Hb Zurich varied from 3.9 to 6.7% for nonsmokers and 9.8 to 19.7% for smokers. Hemolysis was less in smokers, presumably because of stabilization of Hb Zurich by CO. See Huisman et al. (1960), Muller and Kingma (1961), Frick et al. (1962), Rieder et al. (1965), Dickerman et al. (1973), Zinkham et al. (1979, 1980, 1983), Dlott et al. (1983), and Virshup et al. (1983).

Miranda et al. (1994) identified Hb Zurich in a 38-year-old woman who had a hemolytic crisis after administration of an antibiotic for urinary tract infection. This hemoglobin variant was first identified by protein analysis and then by DNA sequencing.

Aguinaga et al. (1998) studied 4 members of a Kentucky family whom they had identified as Hb Zurich carriers. During pregnancy, the proband developed hemolytic anemia with Heinz bodies when treated for a urinary tract infection with sulfonamide. Because of severe anemia, the patient was transfused several times and ultimately splenectomized. The Kentucky family studied in this report was part of a larger kindred that was known to contain 19 members who were Hb Zurich carriers.

Zinkham et al. (1979) demonstrated in vitro thermal denaturation of Hb Zurich as a cause of anemia during fever.


.0311   BETA-ZERO-THALASSEMIA

HBB, LYS17TER
SNP: rs33986703, gnomAD: rs33986703, ClinVar: RCV000016655, RCV000020337, RCV000507505, RCV000763255, RCV001004355, RCV002288498

This variant was found in Chinese with beta-zero-thalassemia (613985). Chang et al. (1979) and Chang and Kan (1979) presented evidence that beta-zero-thalassemia is a nonsense mutation, the first identified in man. By molecular hybridization they showed that the beta gene is present. In different patients variable amounts of beta-like globin mRNA is present. They sequenced mRNA and found that noncoding regions at both ends were normal but at the position corresponding to amino acid no. 17, the normal lysine codon AAG was converted to UAG, a terminator. Such a nonsense mutation should be overcome by means of suppressor tRNA which allows the ribosome to read through a terminator codon by inserting an amino acid. In vitro addition of a serine suppressor tRNA from yeast resulted in human beta-globin synthesis. Cell-free assays with suppressor tRNAs may be useful for detecting nonsense mutations in other human genetic disorders. Steger et al. (1993) showed that this AAG-to-TAG nonsense mutation and the hemoglobin E mutation, common causes of beta(+)-thalassemia and beta-zero-thalassemia in Southeast Asia, can be detected using allele-specific PCR, known also as the amplification refractory mutation system (ARMS).

Krawczak et al. (2000) pointed out that this was the first single basepair substitution in a human gene underlying a genetic disorder to be reported. Knowledge of the amino acid substitution responsible for sickle hemoglobin permitted imperfect inference of the nucleotide change because of redundancy of the code.


.0312   BETA-ZERO-THALASSEMIA

HBB, GLN39TER
SNP: rs11549407, gnomAD: rs11549407, ClinVar: RCV000016656, RCV000254827, RCV000379715, RCV001004570, RCV001197268, RCV002221479, RCV002288499, RCV002336086, RCV002476976, RCV003904844

Chehab et al. (1986) found evidence for new mutation in the codon at beta-39 from CAG (glutamine) to the stop codon TAG. The beta-39 nonsense mutation is the second most common beta-thalassemia (613985) lesion in Italy, accounting for a third of cases, and the most common in Sardinia, accounting for 90% of cases there. In Sardinia, the beta-39 mutation has been identified with 9 different haplotypes. All this suggested to Chehab et al. (1986) that beta-39 is a mutation hotspot. Trecartin et al. (1981) found that the form of beta-zero-thalassemia that is predominant in Sardinia is caused by a single nucleotide mutation at the position corresponding to amino acid number 39 and converting a glutamine codon (CAG) to an amber termination codon (UAG). (Epstein et al. (1963) described 'amber' mutants of phage T4 in a frequently cited paper in a Cold Spring Harbor Symposium on Quantitative Biology. The origin of the unusual name 'amber' is, as Witkowski (1990) called it, 'an interesting footnote in the history of molecular biology.' Edgar (1966) recounted that R. H. Epstein and C. M. Steinberg, then at the California Institute of Technology, had promised Harris Bernstein, then at Yale University, that the mutants, if any were found, would be named after his mother. They were found and were named 'amber,' the English equivalent of 'Bernstein.' The other 2 'stop' codons, UGA and UAA, are sometimes referred to as 'opal' and 'ochre,' respectively.) Rosatelli et al. (1992) used denaturing gradient gel electrophoresis (DGGE) followed by direct sequence analysis of amplified DNA to study 3,000 beta-thalassemia chromosomes in the Sardinian population. They confirmed that the predominant mutation, present in 95.7% of beta-thalassemia chromosomes, was gln39-to-ter.


.0313   BETA-ZERO-THALASSEMIA

HBB, TRP15TER
SNP: rs34716011, rs63750783, gnomAD: rs63750783, ClinVar: RCV000016657, RCV000508601, RCV000576738, RCV001004356, RCV003985073

The trp15-to-ter (W15X) mutation that Kazazian et al. (1984) demonstrated in Asian beta-thalassemia (613985) patients was the result of a TGG-to-TAG mutation. Ribeiro et al. (1992) demonstrated the frequent occurrence in central Portugal of beta-zero-thalassemia due to a change of codon 15 for tryptophan to a stop codon; the basis, however, was a TGG-to-TGA mutation.


.0314   BETA-THALASSEMIA, DOMINANT INCLUSION BODY TYPE

HBB, GLU121TER
SNP: rs33946267, gnomAD: rs33946267, ClinVar: RCV000016658, RCV000507274, RCV000984185, RCV001004560

See Kazazian et al. (1986), Fei et al. (1989) and Adams et al. (1990).

Thein et al. (1990) identified the E121X mutation in 3 British families with dominantly inherited inclusion body beta-thalassemia (603902). The clinical features were that of a dominant dyserythropoietic anemia associated with inclusion bodies in normoblasts. The condition was described originally by Weatherall et al. (1973) and was previously labeled dyserythropoietic, congenital, Irish or Weatherall type. The original family reported by Weatherall et al. (1973) was found by Thein et al. (1990) to carry an insertion/deletion mutation with frameshift in the HBB gene (141900.0520).


.0315   BETA-ZERO-THALASSEMIA

HBB, TRP37TER
SNP: rs33974936, ClinVar: RCV000016659, RCV000169502, RCV000506223, RCV000781456, RCV000999750

See Boehm et al. (1986).


.0316   BETA-ZERO-THALASSEMIA

HBB, GLU43TER
SNP: rs33922842, gnomAD: rs33922842, ClinVar: RCV000016660, RCV000506797, RCV000665678, RCV000780310, RCV001004568

Atweh et al. (1988) described a novel nonsense mutation in a Chinese patient with beta-zero-thalassemia (613985): a G-to-T substitution at the first position of codon 43, which changed the glutamic acid coding triplet (GAG) to a terminator codon (TAG). They incorrectly referred to a patient carrying both the beta-17 and the beta-43 nonsense mutation as being a double heterozygote rather than a compound heterozygote.


.0317   BETA-ZERO-THALASSEMIA

HBB, LYS61TER
SNP: rs33995148, ClinVar: RCV000016661, RCV000506527, RCV001078254, RCV002504795

See Gonzalez-Redondo et al. (1988).


.0318   BETA-ZERO-THALASSEMIA

HBB, TYR35TER
SNP: rs33982568, gnomAD: rs33982568, ClinVar: RCV000016662, RCV001078304, RCV001800305

See Fucharoen et al. (1989).


.0319   HEMOGLOBIN HOUSTON

BETA-PLUS-THALASSEMIA, DOMINANT
BETA-HOUSTON-THALASSEMIA
HBB, GLN127PRO
SNP: rs33910569, ClinVar: RCV000016664, RCV000022611, RCV001001456

In a person of British extraction, Kazazian et al. (1989) found a gln127-to-pro mutation as the basis of a 'dominant' form of beta-plus-thalassemia (613985). This form of thalassemia is due to instability of the beta-globin chains containing the particular mutation. Kazazian et al. (1992) again reported on the CAG-CGG missense mutation at codon 127 which caused thalassemia intermedia with hemolysis in 3 generations of a British-American family. They commented that the paucity of high-frequency exon 3 mutations and the worldwide distribution of the few that are observed are probably attributable to their phenotypic severity and lack of increased genetic fitness in relation to malaria.


.0320   BETA-PLUS-THALASSEMIA

HBB, GLN127PRO AND ALA128DEL
SNP: rs34502690, ClinVar: RCV000016665

In a Japanese patient with beta-plus-thalassemia (613985), Hattori et al. (1989) found deletion of nucleotides AGG from codons 127 and 128 (CAG to GCT) resulting in replacement of gln127 and ala128 by proline (CCT).


.0321   BETA-PLUS-THALASSEMIA

HEMOGLOBIN CAGLIARI
HBB, VAL60GLU
SNP: rs33931779, ClinVar: RCV000016666, RCV000016667

In an Italian with beta-plus-thalassemia (613985), Podda et al. (1989, 1991) found a val60-to-glu substitution.


.0322   BETA-ZERO-THALASSEMIA

HBB, LYS8FS
SNP: rs35497102, gnomAD: rs35497102, ClinVar: RCV000016669, RCV000029972, RCV000506563, RCV001004358, RCV002288500

A frameshift mutation, -AA in codon 8, AAG to G, in the HBB gene was found in a Turkish patient with beta-zero-thalassemia (613985) by Orkin and Goff (1981). This mutation was also found in homozygous state in DNA from the archaeologic remains of a child with severe bone pathology consistent with thalassemia (Filon et al., 1995). The remains came from a grave thought to date to the Ottoman period, sometime between the 16th and 19th centuries. From the tooth development, it was estimated that the child died at the age of about 8 years, whereas patients with this mutation would be expected to be transfusion-dependent from early infancy. Filon et al. (1995) also found a rare DNA polymorphism: a C-to-T transition in the second codon of the HBB gene that did not alter the corresponding amino acid. This polymorphism is found in 13% of present-day Mediterranean beta-thalassemia chromosomes and is part of a haplotype (haplotype IV) that is associated with relatively high levels of fetal hemoglobin. The disease may have run a milder course because of linkage to haplotype IV.


.0323   BETA-ZERO-THALASSEMIA

HBB, GLY16FS
SNP: rs35662066, gnomAD: rs35662066, ClinVar: RCV000016670, RCV000173145, RCV000590756, RCV000724162, RCV002336087, RCV002482874, RCV003227603, RCV003415713

A frameshift mutation, -C, codon 16, GGC to GG, in the HBB gene was found in Asian Indians with beta-zero-thalassemia (613985) by Kazazian et al. (1984).


.0324   BETA-ZERO-THALASSEMIA

HBB, SER44FS
SNP: rs80356820, gnomAD: rs80356820, ClinVar: RCV000016671, RCV000169145, RCV000507725, RCV001723571, RCV002504796

Frameshift, -C, codon 44, TCC to TC, was found in a Kurdish patient with beta-zero-thalassemia (613985) by Kinniburgh et al. (1982).


.0325   BETA-ZERO-THALASSEMIA

HBB, 1-BP INS, G, CODONS 8/9
SNP: rs35699606, gnomAD: rs35699606, ClinVar: RCV000016672, RCV000029974, RCV000368084, RCV000479091, RCV001004357, RCV002496455, RCV003221786, RCV003964816

Frameshift, +G, codons 8/9, AAGTCT to AAGGTCT was found in an Asian Indian with beta-zero-thalassemia (613985) by Kazazian et al. (1984).


.0326   BETA-ZERO-THALASSEMIA

HBB, 4-BP DEL, 41/42CTTT
SNP: rs80356821, ClinVar: RCV000016673, RCV000020328, RCV000508554, RCV001004569, RCV001262999, RCV002426507, RCV002465488, RCV002496380, RCV003914848

Frameshift, -4, codons 41/42, TTCTTT to TT, was found in an Asian Indian with beta-zero-thalassemia (613985) by Kazazian et al. (1984) and in Chinese by Kimura et al. (1983).

Lau et al. (1997) found that the deletion of CTTT at codons 41/42 accounted for 40% of all beta-thalassemia alleles in Hong Kong. Chiu et al. (2002) designed allele-specific primers and a fluorescent probe for detection of this mutation in the HBB gene from maternal plasma by real-time PCR. Using this method, they showed that beta-thalassemia major could be excluded from fetal inheritance by demonstrating absence of inheritance of the paternally transmitted mutation. By studying circulating fetal DNA in the maternal plasma for this mutation, Chiu et al. (2002) added beta-thalassemia to the list of disorders that could be prenatally diagnosed using this noninvasive method, which had previously demonstrated usefulness in diagnosing sex-linked diseases (Costa et al., 2002) and fetal rhesus D status (Lo et al., 1998).


.0327   BETA-ZERO-THALASSEMIA

HBB, GLU6FS
SNP: rs63749819, gnomAD: rs63749819, ClinVar: RCV000016674, RCV000576555, RCV001004359, RCV001008068, RCV002496381

Frameshift, -A, codon 6, GAG to GG, was found in Mediterranean patients by Kazazian et al. (1983). Bouhass et al. (1990) found the same mutation in an Algerian patient who was a genetic compound. Rosatelli et al. (1992) found that this mutation accounted for 2.1% of mutations carried by 3,000 beta-thalassemia chromosomes from the Sardinian population. Romey et al. (1993) described an improved procedure that allows the detection of single basepair deletions on nondenaturing polyacrylamide gels and demonstrated its applicability for identifying this mutation.


.0328   BETA-ZERO-THALASSEMIA

HBB, PHE71FS
SNP: rs33969853, ClinVar: RCV000016675, RCV000507557, RCV000576855, RCV002426508

Frameshift, +A, codons 71/72, TTAGT to TTTAAGT, was found in Chinese by Cheng et al. (1984).


.0329   BETA-ZERO-THALASSEMIA

HBB, LEU106FS
SNP: rs35225141, ClinVar: RCV000016668, RCV000506185, RCV000589491

Frameshift, +G, codons 106/107, CTGGGC to CTGGGGG, was found in American blacks by Wong et al. (1987).


.0330   BETA-ZERO-THALASSEMIA

HBB, ALA76FS
SNP: rs281864901, gnomAD: rs281864901, ClinVar: RCV000016676, RCV000169256, RCV000508493

Frameshift, -C, codon 76, GCT to GT, was found in an Italian by Di Marzo et al. (1988). Rosatelli et al. (1992) found that this mutation was responsible for 0.7% of the mutations carried by 3,000 beta-thalassemia chromosomes in the Sardinian population.


.0331   BETA-ZERO-THALASSEMIA

HBB, TRP37FS
SNP: rs63750532, ClinVar: RCV000016688, RCV000508367, RCV000781455, RCV001004345, RCV001078307, RCV002504797

Frameshift, -G, codon 37, TGG to G, was found in a Kurdish patient by Rund et al. (1989, 1991).


.0332   BETA-ZERO-THALASSEMIA

HBB, PRO5FS
SNP: rs34889882, gnomAD: rs34889882, ClinVar: RCV000016678, RCV000506399, RCV000586913, RCV001004360, RCV002476977, RCV003974832

Frameshift, -CT, codon 5, CCT to CC, was found in a Mediterranean patient by Kollia et al. (1989).


.0333   BETA-ZERO-THALASSEMIA

HBB, VAL11FS
SNP: rs34856846, gnomAD: rs34856846, ClinVar: RCV000016679, RCV000507506, RCV000781438, RCV001078331

Frameshift, -T, codon 11, GTT to GT, was found in a Mexican patient by Economou et al. (1990).


.0334   BETA-ZERO-THALASSEMIA

HBB, TYR35FS
SNP: rs267607297, gnomAD: rs267607297, ClinVar: RCV000016680, RCV000586096, RCV000759790

Frameshift, -C, codon 35, TAC to TA, was found in Indonesia by Yang et al. (1989).


.0335   BETA-ZERO-THALASSEMIA

HEMOGLOBIN GENEVA
HBB, ASP114FS
SNP: rs41443947, ClinVar: RCV000016681

Frameshift, -CT, codon 114, CTG to G, was found in a French patient by Beris et al. (1988). Hb Geneva is an unstable hemoglobin producing a hemolytic anemia with inclusion bodies in the peripheral blood after splenectomy. Heterozygotes show manifestations of a thalassemia-like disorder.


.0336   BETA-ZERO-THALASSEMIA

HBB, LEU14FS
SNP: rs35383398, gnomAD: rs35383398, ClinVar: RCV000016683, RCV000780312, RCV001078383, RCV003556029

Frameshift, +G, codon 14/15, CTGTGG to CTGGTGG, was found in Chinese by Chan et al. (1988).


.0337   BETA-ZERO-THALASSEMIA

HBB, TRP37FS
SNP: rs63750099, ClinVar: RCV000016684, RCV001078349, RCV003114196

Frameshift, -7 nucleotides from codons 37-39, TGGACCCAG, was found in a Turkish patient by Schnee et al. (1989).


.0338   BETA-ZERO-THALASSEMIA

HBB, ASP94FS
SNP: rs34533941, ClinVar: RCV000016685, RCV002513069

Frameshift, +TG, codon 94 (GAC), was found in a Mediterranean patient by Pirastu et al. (1990).


.0339   BETA-ZERO-THALASSEMIA

HBB, GLY64FS
SNP: rs36107977, ClinVar: RCV000016686, RCV001078257

Frameshift, -G, codon 64, GGC to GC, was found in a Swiss woman heterozygous for beta-thalassemia by Chehab et al. (1989). This was a spontaneous mutation as originally described by Tonz et al. (1973). The father was 45 years old when the proband was born. By haplotyping, Chehab et al. (1989) showed, furthermore, that the mutation had arisen on the father's chromosome 11.


.0340   BETA-ZERO-THALASSEMIA

HBB, VAL109FS
SNP: rs63751201, ClinVar: RCV000016687, RCV002284171

Frameshift, -G, codon 109, GTG to TG, found in a Lithuanian by Kazazian et al. (1989).


.0341   BETA-ZERO-THALASSEMIA

HBB, PRO36FS
SNP: rs63750532, ClinVar: RCV000016688, RCV000508367, RCV000781455, RCV001004345, RCV001078307, RCV002504797

Frameshift, -T, codon 36/37, CCTTGG to CCTGG, was found in Iranian Kurds by Rund et al. (1989, 1991).


.0342   BETA-ZERO-THALASSEMIA

HBB, ALA27FS
SNP: rs35532010, ClinVar: RCV000016689, RCV000169441, RCV000508423, RCV000780308, RCV001004352

Frameshift, +C, codons 27/28, GCCCTG to GCCCCTG, was found in Chinese by Cai et al. (1989).


.0343   BETA-ZERO-THALASSEMIA

HBB, PHE71FS
SNP: rs1554917888, rs33969853, ClinVar: RCV000016690, RCV001078312

Frameshift, +T, codon 71, TTT to TTTT, was found in Chinese by Kazazian (1990).


.0344   BETA-ZERO-THALASSEMIA

HBB, MET1ARG
SNP: rs33941849, ClinVar: RCV000016691, RCV000505904, RCV000664667, RCV001004361

This initiator codon mutant, ATG to AGG, was found in Chinese individuals by Kazazian (1990).


.0345   BETA-ZERO-THALASSEMIA

BETA-THALASSEMIA, LERMONTOV TYPE
HBB, MET1THR
SNP: rs33941849, ClinVar: RCV000016692, RCV000016693, RCV000029976, RCV000508042, RCV002465492

This initiator codon mutant, ATG to ACG, was found in Yugoslavians with beta-zero-thalassemia (613985) by Jankovic et al. (1989). The same mutation was found by Beris et al. (1993) in a father and daughter of a family originating from Bern, Switzerland. Unlike the first reported family, of Yugoslavian origin, the Swiss patients had high Hb F levels. The mutation converted the initiator methionine to threonine and abolished an NcoI recognition site.

(In the case of many other genes in which the mutations have been characterized on the basis of the gene itself, the codon count begins with the initiator methionine. In such a system, this mutation would be designated met1-to-thr and the hemoglobin S mutation would be designated glu7-to-val.)

Molchanova et al. (1998) characterized the beta-thalassemia present in 3 generations of a branch of the family of the Russian poet Mihail Yurievich Lermontov. The hematologic data for affected members of 3 generations were compatible with a beta-thal heterozygosity. Sequence analysis showed an ATG-to-ACG change in the initiation codon. The family in which it was first observed by Jankovic et al. (1989, 1990) was said to have been of Croatian origin. In that family, the mutation was accompanied by a CAC-to-CAT change in codon 2 of the same chromosome; this common polymorphism was not seen in the Russian family.


.0346   BETA-ZERO-THALASSEMIA

HBB, IVS1, G-A, +1
SNP: rs33971440, gnomAD: rs33971440, ClinVar: RCV000016694, RCV000020340, RCV000390929, RCV001004350, RCV001329338, RCV002288501, RCV002476978

Splice junction mutant, G to A, position 1 of IVS1, was found by Orkin et al. (1982) in a Mediterranean patient.


.0347   BETA-ZERO-THALASSEMIA

HBB, IVS1, G-T, +1
SNP: rs33971440, gnomAD: rs33971440, ClinVar: RCV000016695, RCV000169505, RCV000507580, RCV001004349, RCV002444432, RCV002482875, RCV003924839

Splice junction mutant, G to T, at position 1 of IVS1 was found in an Asian Indian and in Chinese by Kazazian et al. (1984).


.0348   BETA-ZERO-THALASSEMIA

HBB, IVS2, G-A, +1
SNP: rs33945777, gnomAD: rs33945777, ClinVar: RCV000016696, RCV000020332, RCV000255349, RCV001004566, RCV001723572, RCV001731303, RCV002288502, RCV002476979

A splice junction mutant, G to A, at position 1 of IVS2 was found in a Mediterranean by Treisman et al. (1982), in a Tunisian by Chibani et al. (1988), and in an American black by Thein et al. (1988). The same mutation was found by Hattori et al. (1992), who referred to the mutation as IVS2-1 (G-A).

This is one of the earliest mutations at a 5-prime splice site to be described. In an analysis of 101 different examples of point mutations that lie in the vicinity of mRNA splice junctions and that have been held to be responsible for human genetic disease by altering the accuracy or efficiency of mRNA splicing, Krawczak et al. (1992) found that 62 were located at 5-prime splice sites, 26 at 3-prime splice sites, and 13 resulted in the creation of novel splice sites. They estimated that up to 15% of all point mutations causing human genetic disease result in an mRNA splicing defect. Of the 5-prime splice site mutations, 60% involve the invariant GT dinucleotides.

Sierakowska et al. (1996) found that treatment of mammalian cells stably expressing the IVS2-654 beta HBB gene with antisense oligonucleotides targeted at the aberrant splice sites restored correct splicing in a dose-dependent fashion, generating correct human beta-globin mRNA and polypeptide. Both products persisted for up to 72 hours after treatment. The oligonucleotides modified splicing by a true antisense mechanism without overt unspecific effects on cell growth and splicing of other pre-mRNAs. Sierakowska et al. (1996) stated that this novel approach in which antisense oligonucleotides are used to restore rather than to downregulate the activity of the target gene is applicable to other splicing mutants and is of potential clinical interest.

This mutation is frequent among patients in southern China and Thailand, accounting for 20% of beta-thalassemia in some regions. It causes aberrant RNA splicing. Lewis et al. (1998) modeled this mutation in mice, replacing the 2 (cis) murine adult beta-globin genes with a single copy of the human mutant HBB gene. No homozygous mice survived postnatally. Heterozygous mice carrying this mutant gene produced reduced amounts of mouse beta-globin chains and no human beta globin, and had a moderately severe form of beta-thalassemia. Heterozygotes showed the same aberrant splicing as their human counterparts and provided an animal model for testing therapies that correct splicing defects at either the RNA or DNA level.


.0349   BETA-ZERO-THALASSEMIA

HBB, IVS1, T-G, +2
SNP: rs33956879, gnomAD: rs33956879, ClinVar: RCV000016697, RCV000759805, RCV001001413, RCV001078334

Splice junction mutant, T to G, at position 2 of IVS1 was found in a Tunisian by Chibani et al. (1988).


.0350   BETA-ZERO-THALASSEMIA

HBB, IVS1, T-C, +2
SNP: rs33956879, gnomAD: rs33956879, ClinVar: RCV000030003, RCV000506748, RCV002496456

Splice junction mutant, T to C, at position 2 of IVS1 was found in an American black by Gonzalez-Redondo et al. (1989). Of 33 thalassemic chromosomes in Algerian patients studied by Bouhass et al. (1990), 7 carried the T-to-C transition at position 2 in IVS1. Thus, the mutation may be common in the Algerian population. They observed 2 patients who were homozygous for the substitution and had no detectable Hb A by standard electrophoresis procedures. Interestingly, the other 2 possible changes at this position have also been observed; see 141900.0349 and 141900.0392.


.0351   BETA-ZERO-THALASSEMIA

HBB, IVS1, 17-BP DEL
SNP: rs1554918032, rs63750915, ClinVar: RCV000016699, RCV001078335

Deletion of 17 nucleotides that removed the acceptor splice site from IVS1 was found in a Kuwaiti by Kazazian and Boehm (1988).


.0352   BETA-ZERO-THALASSEMIA

HBB, IVS1, 25-BP DEL
SNP: rs193922563, rs63750223, ClinVar: RCV000016700, RCV000030009, RCV001052793, RCV001731304, RCV002371773, RCV002465489

Deletion of 25 nucleotides that removed the acceptor splice site of IVS1 was found in an Asian Indian by Orkin et al. (1983).


.0353   BETA-ZERO-THALASSEMIA

HBB, IVS2, A-G, -2
SNP: rs33914668, gnomAD: rs33914668, ClinVar: RCV000016701, RCV000020336, RCV000508360, RCV001004562, RCV002504815, RCV003389313

Change from CCACAGC to CCACGGC (A to G at position -2) in the acceptor splice site of IVS2 was found in American blacks by Antonarakis et al. (1984) and Atweh et al. (1985).

This is one of the earliest-described examples of mutation in the 3-prime splice site affecting mRNA splicing. In an analysis of 101 different examples of point mutations occurring in the vicinity of mRNA splice junctions and resulting in human genetic disease, Krawczak et al. (1992) found that 26 involved 3-prime splice sites.


.0354   BETA-ZERO-THALASSEMIA

HBB, IVS2, A-C, -2
SNP: rs33914668, gnomAD: rs33914668, ClinVar: RCV000016702, RCV000020335, RCV000507767, RCV001290616

Change from CCACAGC to CCACCGC (A to C at position -2) at acceptor splice site of IVS2 was found in American blacks by Padanilam and Huisman (1986).


.0355   BETA-ZERO-THALASSEMIA

HBB, IVS1, 44-BP, SS DEL
SNP: rs63751076, ClinVar: RCV000016703, RCV001078435, RCV003317038

Deletion of 44 nucleotides that removed the IVS1 donor splice site was found in a Mediterranean patient by Kazazian and Boehm (1988).


.0356   BETA-ZERO-THALASSEMIA

HBB, IVS1, G-A, -1
SNP: rs33943001, gnomAD: rs33943001, ClinVar: RCV000016704, RCV000508208, RCV000587419

In an Egyptian child with thalassemia major, Deidda et al. (1990) found heterozygosity for a G-to-A substitution at position -1 of IVS1, which altered the conserved dinucleotide AG present in the consensus acceptor sequence. The other chromosome carried the T-to-C mutation at position 6 of the first intervening sequence (IVS1) (141900.0360). The latter mutation was associated with haplotype 6, frequently observed in Mediterranean areas; the new mutation was associated with haplotype 1. This gene can be added to the list of mutations that can be identified by Southern analysis using AflII.


.0357   BETA-PLUS-THALASSEMIA

HBB, IVS1, G-C, +5
SNP: rs33915217, gnomAD: rs33915217, ClinVar: RCV000016705, RCV000020341, RCV000255746, RCV000763253, RCV001004348, RCV001794453, RCV002288503, RCV002444433, RCV003445071

A G-to-C change at position 5 of the donor site consensus sequence of IVS1 (CAG-GTTGGT to CAG-GTTGCT) was found in an Asian Indian with beta-plus-thalassemia (613985) by Kazazian et al. (1984) and in a Chinese with the same disorder by Cheng et al. (1984).


.0358   BETA-PLUS-THALASSEMIA

HBB, IVS1, G-T, +5
SNP: rs33915217, gnomAD: rs33915217, ClinVar: RCV000016706, RCV000030005, RCV000505898, RCV000984182

This mutation is a cause of beta-plus-thalassemia (613985). A G-to-T change at position 5 of the donor site consensus sequence of IVS1 (CAG-gttggt-to-CAG-gttgtt) was found in a Mediterranean patient and an Anglo-Saxon patient by Atweh et al. (1987) and in an American black by Gonzalez-Redondo et al. (1988). The 2 cases of Atweh et al. (1987) were in different RFLP backgrounds, suggesting that they represented independent mutations. Atweh et al. (1987) showed that after transfer of the cloned genes into HeLa cells, followed by transient expression, partial inactivation of the normal donor splice site of IVS1 and activation of 2 major and 1 minor cryptic splice sites occur. The effects of this mutation on mRNA splicing were similar to those of another beta-thalassemia gene with a G-to-C transition at the same position (141900.0357). In a rare case of beta-thalassemia in a German family, Eigel et al. (1989) found a G-to-T transversion at the intron 1 donor site of the beta-globin gene. This may be the same mutation. The patient was homozygous for this mutation and had died at age 27 of heart failure resulting from iron overload.


.0359   BETA-PLUS-THALASSEMIA

HBB, IVS1, G-A, +5
SNP: rs33915217, gnomAD: rs33915217, ClinVar: RCV000016707, RCV000030004, RCV001216321

A G-to-A change at position 5 of the donor site consensus sequence of IVS1 (CAG-GTTGGT to CAGGTTGAT) was found in an Algerian patient with beta-plus-thalassemia (613985) by Lapoumeroulie et al. (1986).


.0360   BETA-PLUS-THALASSEMIA

HBB, IVS1, T-C, +6
SNP: rs35724775, gnomAD: rs35724775, ClinVar: RCV000016708, RCV000415353, RCV000417932, RCV000763252, RCV001004347, RCV001107024, RCV001107025, RCV002247349, RCV002371774, RCV003398525

T-to-C change at position 6 of the donor site consensus sequence of IVS1 (CAG-GTTGGT to CAG-GTTGGC) was found in a Mediterranean patient by Orkin et al. (1982).


.0361   BETA-PLUS-THALASSEMIA

HBB, IVS2, C-A, -3
SNP: rs33913413, gnomAD: rs33913413, ClinVar: RCV000016709, RCV000029987, RCV000506607, RCV000984183, RCV002496382, RCV003398526

A C-to-A change at position -3 in the acceptor splice site of IVS2 (CAG to AAG) was found in an Iranian, an Egyptian, and an American black by Gonzalez-Redondo et al. (1988) and Wong et al. (1989).


.0362   BETA-PLUS-THALASSEMIA

HBB, IVS1, T-G, -3
SNP: rs34527846, gnomAD: rs34527846, ClinVar: RCV000016710, RCV000030011, RCV002222330, RCV002477023

A T-to-G change at position -3 in the acceptor splice site of IVS1 (TAG to GAG) was found in a Saudi Arabian patient with beta-plus-thalassemia (613985) by Wong et al. (1989). Indeed, Wong et al. (1989) identified 2 different nucleotide substitutions in consensus acceptor splice sequences of the beta-globin gene leading to beta-thalassemia. One was at the IVS1/exon 2 junction and the other at the IVS2/exon 3 junction (141900.0361). Both mutations were single nucleotide substitutions, T-to-G and C-to-A, at position -3 immediately adjacent to the invariant AG dinucleotide. For the IVS2/exon 3 mutation, abnormal splicing into the cryptic splice site at IVS2 nucleotide 579 was demonstrated.


.0363   BETA-PLUS-THALASSEMIA

HBB, IVS1, C-A, -8
SNP: rs34793594, ClinVar: RCV000016711, RCV001078323, RCV003556030

A C-to-A change at position -8 in the acceptor splice site of IVS2 was found in an Algerian patient with beta-plus-thalassemia (613985) by Beldjord et al. (1988).


.0364   BETA-PLUS-THALASSEMIA

HBB, IVS1, G-A, +110
SNP: rs35004220, gnomAD: rs35004220, ClinVar: RCV000016712, RCV000020343, RCV000030008, RCV000763251, RCV000799079, RCV001004346, RCV001262998, RCV002288504, RCV002371775

A G-to-A change at position 110 of IVS1 was found in a Mediterranean patient with beta-thalassemia (613985) by Spritz et al. (1981) and Westaway and Williamson (1981). The mutation created a new splice acceptor site.

Kaplan et al. (1990) studied the molecular basis of beta-thalassemia minor, which has a frequency of about 1% among French Canadians residing in Portneuf County of Quebec Province. They showed that there were 2 different beta-thalassemia mutations segregating in the population: an RNA processing mutation involving nucleotide 110 of IVS1 on haplotype 1 and a point mutation leading to chain termination through a nonsense codon at position 39 (141900.0312), occurring on haplotype 2.


.0365   BETA-ZERO-THALASSEMIA

HBB, IVS1, T-G, +116
SNP: rs35456885, ClinVar: RCV000016713, RCV000665080

A T-to-G change at position 116 of IVS1 in the HBB gene was found in a Mediterranean patient by Metherall et al. (1986). The mutation created a new acceptor splice site, which resulted in the inclusion of IVS1 sequences in mature mRNA, producing a frameshift within exon 2 and a termination codon 34 amino acids downstream from the abnormal splice.


.0366   BETA-PLUS-THALASSEMIA

HBB, IVS2, T-G, +705
SNP: rs35328027, ClinVar: RCV000016714, RCV000029979, RCV000985748

A T-to-G change at position 705 of IVS2 was found in a Mediterranean patient with beta-plus-thalassemia (613985) by Dobkin et al. (1983). The mutation created a new acceptor splice site.


.0367   BETA-PLUS-THALASSEMIA

HBB, IVS2, C-G, +745
SNP: rs34690599, ClinVar: RCV000016715, RCV000029978, RCV000506445, RCV001004564, RCV002272021, RCV002288505, RCV002476980

A C-to-G change at position 745 of IVS2 was found in a Mediterranean patient with beta-plus-thalassemia (613985) by Orkin et al. (1982). The mutation created a new acceptor splice site.


.0368   BETA-ZERO-THALASSEMIA

HBB, IVS2, C-T, +654
SNP: rs34451549, ClinVar: RCV000016716, RCV000020334, RCV000029984, RCV000794203, RCV001004565, RCV003407341

A C-to-T change at position 654 of IVS2 was found in a Chinese by Cheng et al. (1984).


.0369   BETA-PLUS-THALASSEMIA

HBB, GGT24GGA AND GLY24GLY
SNP: rs33951465, gnomAD: rs33951465, ClinVar: RCV000016717, RCV000030002, RCV000508672, RCV001004354, RCV002496383

In an American black patient with beta-plus-thalassemia (613985), Goldsmith et al. (1983) found a change in codon 24 from GGT to GGA. Although silent in terms of changing the amino acid sequence, the mutation affected processing of mRNA.


.0370   BETA-PLUS-THALASSEMIA

HBB, -101C-T, PROMOTER
SNP: rs63751208, gnomAD: rs63751208, ClinVar: RCV000016719, RCV000169081, RCV000820736, RCV002496384, RCV003904845

Gonzalez-Redondo et al. (1989) found a C-to-T change in nucleotide -101 in an asymptomatic Turkish carrier of beta-thalassemia. This is one of the transcriptional mutants causing beta-thalassemia. Ristaldi et al. (1990) showed that this mutation is a relatively frequent cause of beta-thalassemia in the Italian population, where it is always associated with haplotype 1. Compound heterozygosity for this promoter mutation and a mutation for severe beta-thalassemia results in a mild form of thalassemia intermedia (Murru et al., 1991). In studies of infants of Italian couples, 1 member of which was heterozygous for this promoter mutation, Murru et al. (1993) demonstrated that mutation leads to a more severe defect in beta-globin chain production in infancy than in adulthood. The moment of transition from the fetal-infant to the adult pattern of expression seems to be at about 2 years of age. This age-related pattern of expression had not been detected for other beta-thalassemia mutations. Assuming the existence of different distal CACCC box binding proteins with an activating function on the beta-globin gene promoter in fetal and adult ages, Murru et al. (1993) speculated that the fetal type interacts less efficiently with the mutated CACCC promoter as compared with the adult one. They suggested that the findings permit one to predict a mild phenotype even when HbA is absent in the newborn.

Maragoudaki et al. (1999) reported the clinical, hematologic, biosynthetic, and molecular data on 25 double heterozygote beta-thalassemia intermedia patients and 45 beta-thalassemia heterozygotes with the C-to-T substitution at nucleotide position -101 from the cap site, in the distal CACCC box of the HBB promoter. This mutation is considered the most common among the silent beta-thalassemia mutations in Mediterranean populations. Of the 25 compound heterozygotes for the promoter mutation and common severe beta-thalassemia mutations, all but 1 had mild thalassemia intermedia preserving hemoglobin levels around 9.5 g/dl and hemoglobin F levels less than 25%. Strict assessment of hematologic and biosynthetic findings in the heterozygotes for the promoter mutation demonstrated that less than half of them had completely normal (silent) hematology.


.0371   BETA-PLUS-THALASSEMIA

HBB, -92C-T
SNP: rs34883338, ClinVar: RCV000016720, RCV000445639, RCV000589915, RCV003476899

Kazazian (1990) found a C-to-T change at position -92 in a Mediterranean patient with beta-plus-thalassemia (613985).


.0372   BETA-PLUS-THALASSEMIA

HBB, -88C-T
SNP: rs33944208, gnomAD: rs33944208, ClinVar: RCV000016718, RCV000020324, RCV000507151, RCV000781453, RCV002390113

Orkin et al. (1984) found a C-to-T change at position -88 in an American black and an Asiatic Indian with beta-plus-thalassemia (613985).


.0373   BETA-PLUS-THALASSEMIA

HBB, -88C-A
SNP: rs33944208, gnomAD: rs33944208, ClinVar: RCV000016721, RCV000445645, RCV000505872, RCV000762846, RCV000781451, RCV003488595

In a Kurdish Jew with beta-plus-thalassemia (613985), Rund et al. (1989, 1991) found a C-to-A change at position -88.


.0374   BETA-PLUS-THALASSEMIA

HBB, -87C-G
SNP: rs33941377, gnomAD: rs33941377, ClinVar: RCV000016722, RCV000029951, RCV000445653, RCV000507653, RCV002496385

In a Mediterranean patient with beta-plus-thalassemia (613985), Orkin et al. (1982) found a C-to-G change at position -87.


.0375   BETA-PLUS-THALASSEMIA

HBB, -86C-G
SNP: rs33994806, ClinVar: RCV000016723, RCV000029948, RCV000505925

In a Lebanese patient with beta-plus-thalassemia (613985), Kazazian (1990) found a C-to-G change at position -86.


.0376   BETA-PLUS-THALASSEMIA

HBB, -31A-G
SNP: rs33981098, ClinVar: RCV000016724, RCV000445643, RCV000506722, RCV001255596

In a Japanese patient with beta-plus-thalassemia (613985), Takihara et al. (1986) found an A-to-G change at position -31. Also see Yamashiro et al. (1989).


.0377   BETA-PLUS-THALASSEMIA

HBB, -30T-A, PROMOTER
SNP: rs33980857, ClinVar: RCV000016725, RCV000029962, RCV000508486, RCV001000147

In a Turkish patient with beta-plus-thalassemia (613985), Fei et al. (1988) found a T-to-A change at position -30 (a TATA box mutation). Fedorov et al. (1992) found the T-30A mutation in a Karachai patient with beta-thalassemia intermedia.


.0378   BETA-PLUS-THALASSEMIA

HBB, -30T-C, PROMOTER
SNP: rs33980857, ClinVar: RCV000016726, RCV001078342, RCV001284493

In a Chinese with beta-plus-thalassemia (613985), Cai et al. (1989) demonstrated a new beta-thalassemia mutation: a T-to-C mutation at position -30 converting a normal TATA box sequence from ATAAA to ACAAA.


.0379   BETA-PLUS-THALASSEMIA

HBB, -29A-G, PROMOTER
SNP: rs34598529, gnomAD: rs34598529, ClinVar: RCV000016727, RCV000020326, RCV000810653, RCV002247350, RCV002415420, RCV002476981

An A-to-G change at position -29 (a TATA box mutation) was found in an American black by Antonarakis et al. (1984) and in a Chinese patient with beta-plus-thalassemia (613985) by Huang et al. (1986).


.0380   BETA-PLUS-THALASSEMIA

HBB, -28A-C, PROMOTER
SNP: rs33931746, gnomAD: rs33931746, ClinVar: RCV000016728, RCV000508592, RCV000589656, RCV001004363, RCV002482876

In a Kurdish Jew with beta-plus-thalassemia (613985), Poncz et al. (1982) found an A-to-C change at position -28 (a TATA box mutation).


.0381   BETA-PLUS-THALASSEMIA

HBB, -28A-G, PROMOTER
SNP: rs33931746, gnomAD: rs33931746, ClinVar: RCV000016729, RCV000029960, RCV000506257, RCV001004362

In Chinese patient with beta-plus-thalassemia, Orkin et al. (1983) found an A-to-G change at position -28 (a TATA box mutation).


.0382   BETA-PLUS-THALASSEMIA

HBB, 3-UNT, T-C, +3
SNP: rs33978907, gnomAD: rs33978907, ClinVar: RCV000016730, RCV000445649, RCV000506540, RCV001004557

In an American black patient with beta-plus-thalassemia (613985), Orkin et al. (1985) found a change from AATAAA to AACAAA in the 3-prime untranslated portion of the gene. This and several others are RNA cleavage and polyadenylation mutants.


.0383   BETA-PLUS-THALASSEMIA

HBB, 3-UNT, A-G, +6
SNP: rs33985472, ClinVar: RCV000016731, RCV000445642, RCV002513070

In a Kurdish patient with beta-plus-thalassemia (613985), Rund et al. (1989, 1991, 1992) found a change from AATAAA-to-AATAAG in the 3-prime untranslated portion of the gene. Rund et al. (1992) used this and another polyadenylation mutation (141900.0417) to investigate the function of the poly(A) signal in vivo and to evaluate the mechanism whereby these mutations lead to a thalassemic phenotype. Analysis of RNA derived from peripheral blood demonstrated the presence of elongated RNA species in patients carrying either mutation. Other aspects of RNA processing (initiation, splicing) were unimpaired.


.0384   BETA-PLUS-THALASSEMIA

HBB, 3-UNT, A DEL, +4
ClinVar: RCV000016732

In an Arab patient with beta-plus-thalassemia (613985), Kazazian (1990) found deletion of an A in the 3-prime RNA cleavage-polyadenylation signal, i.e., a change from AATAAA to AATAA.


.0385   BETA-PLUS-THALASSEMIA

HBB, 3-UNT, G INS, +4
ClinVar: RCV000016733

In a Mediterranean patient with beta-plus-thalassemia (613985), Jankovic et al. (1989) found a change from AATAA to AATGAA in the RNA cleavage-polyadenylation signal.


.0386   BETA-PLUS-THALASSEMIA

HBB, 3-UNT, A-G, +5
SNP: rs63750954, ClinVar: RCV000016734

In a Malaysian patient with beta-plus-thalassemia (613985), Jankovic et al. (1989) found a change from AATAAA to AATAGA in the RNA cleavage-polyadenylation signal.


.0387   BETA-PLUS-THALASSEMIA

HBB, CAP, A-C
SNP: rs34305195, gnomAD: rs34305195, ClinVar: RCV000029957, RCV000508619, RCV001838527

In an Asian Indian patient with beta-plus-thalassemia (613985), Wong et al. (1986) found a cap site mutation, specifically, an A-to-C change at position 1. The first nucleotide of the transcript is designated the cap site; it is usually 60-100 nucleotides 5-prime of the initiator methionine codon in the untranslated part of the transcript. The cap site is the nucleotide to which a 7-methyl-G cap is added to the mRNA transcript. The mutation reported by Wong et al. (1987) is the only cap site mutation reported to date (Kazazian, 1992).


.0388   MOVED TO 141900.0356


.0389   HEMOGLOBIN BIRMINGHAM

HBB, 9-BP DEL
SNP: rs34383403, ClinVar: RCV000016736

Wilson et al. (1990) found loss of leu-ala-his-lys at positions 141, 142, 143, and 144 and their replacement by a gln residue. The changes were the result of a deletion of 9 nucleotides, namely, 2 bp of codon 141, all of codons 142 and 143, and 1 bp of codon 144; the remaining CAG triplet (C from codon 141 and AG from codon 144) codes for the inserted glutamine.


.0390   HEMOGLOBIN GALICIA

HBB, 3-BP DEL
SNP: rs63750837, ClinVar: RCV000016737

In a Spanish patient, Wilson et al. (1990) found that his and val at positions 97 and 98 of the beta-chain had been replaced by a leu residue. The change resulted from the deletion of ACG in codons 97 and 98 and the creation of a remaining triplet CTG (C from codon 97 and TG from codon 98) which codes for the inserted leucine residue. Wilson et al. (1990) considered 2 mechanisms, namely, slipped mispairing in the presence of short repeats, and misreading by DNA polymerase due to a local distortion of the DNA helix, as the basis for the small deletions in hemoglobin Birmingham and hemoglobin Galicia.


.0391   HEMOGLOBIN SOUTH MILWAUKEE

HBB, LEU105PHE
SNP: rs34022507, gnomAD: rs34022507, ClinVar: RCV000016738, RCV000506082

In 4 generations of a family of English ancestry, Honig et al. (1990) found 15 persons with erythrocytosis. Elevated hemoglobin levels were accompanied by leftward-shifted whole blood oxygen equilibrium curves. Phlebotomies for relief of symptoms attributable to erythrocytosis had been necessary in 5 of the affected family members. In the affected individuals, 43% of the beta chains contained a leucine-to-phenylalanine substitution at position 105. Oxygen equilibrium curves demonstrated normal Bohr effect but decreased cooperativity.


.0392   BETA-ZERO-THALASSEMIA

HBB, IVS1, T-A, +2
SNP: rs33956879, gnomAD: rs33956879, ClinVar: RCV000016739, RCV000506130, RCV000665219

Bouhass et al. (1990) described an Algerian patient with beta-zero-thalassemia (613985) who was a genetic compound for the mutation listed as 141900.0327 and a new mutation consisting of a T-to-A transversion at position 2 of IVS1.


.0393   HEMOGLOBIN DHONBURI

HEMOGLOBIN NEAPOLIS
HBB, VAL126GLY
SNP: rs121909806, rs33925391, gnomAD: rs33925391, ClinVar: RCV000016741, RCV000674175, RCV000756239, RCV001260263

While investigating the mechanism of a beta-thalassemia intermedia phenotype in a 34-year-old Thai male, Bardakdjian-Michau et al. (1990) discovered a new beta-hemoglobin variant, val126-to-gly, which they called Hb Dhonburi. The variant was unstable but exhibited normal oxygen-binding properties. Pagano et al. (1991) found the same amino acid substitution in 3 unrelated families from southern Italy and dubbed it Neapolis. A GTG-to-GGG mutation was responsible for the change. The 8 heterozygous patients showed hematologic and biosynthetic alterations of mild beta-thalassemia. The characteristics were very similar to those of Hb E (141900.0071), Hb Knossos (141900.0149), and Hb Malay (141900.0168), all of which have a single base substitution causing amino acid replacement and alternative splicing of the precursor beta-mRNA by activating cryptic donor sites in exon 1.

Moghimi et al. (2004) demonstrated this variant in a family from northern Iran.


.0394   HEMOGLOBIN IOWA

HBB, GLY119ALA
SNP: rs33947020, gnomAD: rs33947020, ClinVar: RCV000016743

Plaseska et al. (1990) found a gly-to-ala mutation at position beta119 in a black infant and her mother. The baby was also heterozygous for Hb S (141900.0243). The change in hemoglobin Iowa did not affect stability or oxygen-carrying properties; hematologic data were normal in the mother and child.

Somjee et al. (2004) described Hb Iowa in compound heterozygous state, not with Hb S as in the initial report, but with Hb C (141900.0038). The patient was an African American girl, originally diagnosed as homozygous Hb C during neonatal screening. Both cases indicated that there were no abnormal hematologic manifestations associated with this rare hemoglobin variant. However, in both cases, Hb Iowa was mistaken for Hb F during routine neonatal screening. Neonatal misidentification of Hb Iowa led to misdiagnosis of sickle cell disease in the patient of Plaseska et al. (1990) and Hb C in the patient of Somjee et al. (2004).


.0395   BETA-THALASSEMIA

HBB, 1-BP INS, A, CODON 47
SNP: rs35894115, gnomAD: rs35894115, ClinVar: RCV000016744, RCV000505977

In a Suriname carrier of beta-thalassemia (613985), Losekoot et al. (1990) detected a frameshift insertion in the HBB gene: a single nucleotide (+A) at codon 47 which caused the formation of a termination codon at position 52.


.0396   HEMOGLOBIN CALAIS

HBB, ALA76PRO
SNP: rs35286210, gnomAD: rs35286210, ClinVar: RCV000016740

In a 43-year-old woman suffering from chronic anemia since the age of 20, Wajcman et al. (1991) found this new hemoglobin variant which displays decreased oxygen affinity.


.0397   HEMOGLOBIN ZENGCHENG

HBB, LEU114MET
SNP: rs33917394, gnomAD: rs33917394, ClinVar: RCV000016486, RCV000016745

This variant was detected in a cord blood sample from a Chinese newborn tested by IEF and reversed phase high performance liquid chromatography (Plaseska et al., 1990). This mutation occurs with another mutation in Hb Masuda (141900.0172).


.0398   HEMOGLOBIN TERRE HAUTE

BETA-PLUS-THALASSEMIA
HBB, LEU106ARG
SNP: rs33941844, ClinVar: RCV000016746, RCV000016747

Adams et al. (1978, 1979) described a hemoglobin variant responsible for severe beta-thalassemia with dominant inheritance. They concluded that the mutation, which they referred to as Hb Indianapolis (see 141900.0117), carried a cys112-to-arg mutation. Subsequent description of 2 families, which indeed carried this mutation but were minimally affected, prompted restudy of the original family. Both of the original carriers of the variants had succumbed to their severe anemia. However, by the use of PCR, enough DNA was recovered from a 10-year-old bone marrow microscope slide to sequence the third exon of the beta-globin gene. These studies showed substitution of arginine for leucine at position 106 of the beta-globin chain. In order to avoid confusion with the cys112-to-arg mutation, to which the name Hb Indianapolis was firmly attached, Coleman et al. (1991) renamed the original variant hemoglobin Hb Terre Haute. The dominantly inherited beta-thalassemias that are due to highly unstable variant beta chains, such as HB Indianapolis, result from the rapid catabolism of the beta chains and consequent erythroblast destruction within the bone marrow. These differ from the classic unstable hemoglobin variants in which most damage occurs to erythrocytes in the circulation, resulting in hemolytic anemia rather than impaired erythropoiesis.


.0399   BETA-PLUS-THALASSEMIA

HBB, 3-UNT, A-G, +4
SNP: rs63751128, ClinVar: RCV000016748, RCV000445654, RCV000506983, RCV001193152

In a Dutch patient with a mild, nontransfusion dependent beta-thalassemia phenotype (613985), Losekoot et al. (1991) found a mutation in the cleavage-polyadenylation sequence. The mutation, AATAAA-to-AATGAA, was detected using denaturing gradient gel electrophoresis (DGGE) and direct sequencing of genomic DNA amplified by PCR.


.0400   HEMOGLOBIN VALLETTA

HBB, THR87PRO
SNP: rs35553496, gnomAD: rs35553496, ClinVar: RCV000016749, RCV000029973, RCV000508492, RCV002504798

Kutlar et al. (1991) described a new hemoglobin variant called Hb Valletta, which is characterized by a threonine-to-proline substitution at position 87 of the beta chain. This mutation was found to be linked to that of the gamma-chain variant Hb F-Malta-I (142250.0014) which has a his-to-arg mutation at position 117 of the G-gamma chain. The 2 genes are 27 to 28 kb apart. No chromosomes with one or the other mutation alone were identified.


.0401   HEMOGLOBIN JACKSONVILLE

HBB, VAL54ASP
SNP: rs34037627, ClinVar: RCV000016750

In a 12-year-old black male with splenomegaly and anemia, Gaudry et al. (1990) found a hemoglobin variant manifest by electrophoretic abnormality. This unstable hemoglobin was found to have a substitution of aspartic acid for valine at position 54 of the beta chain.


.0402   HEMOGLOBIN CHESTERFIELD

HBB, LEU28ARG
SNP: rs33916412, ClinVar: RCV000016751

Thein et al. (1991) reported a patient with severe heterozygous beta-thalassemia characterized by large inclusion bodies and resulting in a single base substitution, CTG to CGG, in codon 28 in exon 1. The mutant hemoglobin, called Hb Chesterfield, had an unstable beta chain. The patient was a 34-year-old English woman who had presented at the age of 7 years with abdominal pain, anemia, jaundice, and hepatosplenomegaly. She had been transfusion-dependent since the age of 10. Because of increasing transfusion requirements, a splenectomy was performed at the age of 13. Cholecystectomy was required at the age of 28.


.0403   HEMOGLOBIN QUEBEC-CHORI

HEMOGLOBIN CHORI
HBB, THR87ILE
SNP: rs33993568, gnomAD: rs33993568, ClinVar: RCV000016753

Witkowska et al. (1991) found that sickle cell disease in a 3-year-old girl was due to compound heterozygosity for the Hb S gene and a new mutation called Hb Quebec-Chori. ('Chori' is an acronym for the Children's Hospital Oakland Research Institute.) Although the purified variant had gelling properties similar to those of Hb A, a mixture of it with Hb S resulted in a delay time of polymerization very similar to that of a homogeneous solution of Hb S. The sickle gene was inherited from the father, who was black and originally from Guyana. The new mutant was inherited from the mother, who was white and of English-Irish-French Canadian extraction. By peptide analysis, the new hemoglobin was found to have substitution of isoleucine for threonine-87.


.0404   HEMOGLOBIN REDONDO

HEMOGLOBIN ISEHARA
HBB, HIS92ASN-TO-ASP
SNP: rs33924775, ClinVar: RCV000016756

In a Portuguese patient suffering from a chronic hemolytic anemia, Wajcman et al. (1991) found an unstable hemoglobin which contained a his92-to-asn substitution. The variant readily loses its heme group and a rapid deamidation occurs in vitro, yielding an asp92 semihemoglobin. The oxygen affinity of the patient's red blood cells was increased, leading to stimulation of erythropoiesis and a macrocytic hemolytic disease. Harano et al. (1991) found the same unstable hemoglobin variant in a Japanese female with hemolytic anemia and called it Hb Isehara.

In addition to Hb Redondo, 6 other rare Hb variants had been reported in which deamidation of an asn residue to an asp occurred as a spontaneous posttranslational modification: Hb J (Sardegna) (141850.0036), Hb J (Singapore) (141800.0075), Hb La Roche-sur-Yon (141900.0482), Hb Osler (141900.0211), Hb Providence (141900.0227), and Hb Wayne (141850.0004).


.0405   HEMOGLOBIN COIMBRA

HBB, ASP99GLU
SNP: rs34013622, ClinVar: RCV000016757

In a Portuguese family living in Coimbra, Portugal, Tamagnini et al. (1991) identified a high oxygen affinity hemoglobin variant. Aspartic acid at residue 99 was replaced by glutamic acid in the beta chain. Two affected members had erythrocytosis with hemoglobin levels of 18 to 20 g/dl. A GAT-to-GAA mutation at codon 99 represented the seventh type of substitution at this specific location. From a survey of mutations, Tamagnini et al. (1991) suggested that codons GAC(asp), GAT(asp), GAG(glu), and GAA(glu) are particularly susceptible to mutational events.


.0406   BETA-PLUS-THALASSEMIA

HBB, -32C-A, PROMOTER
SNP: rs34500389, ClinVar: RCV000016752, RCV001078344, RCV003155028

Lin et al. (1992) described a mutation in the TATA box that has the sequence CATAAA and is located about 30 nucleotides upstream of the cap site. The mutation changed CATAAA to AATAAA.


.0407   HEMOGLOBIN CLEVELAND

HBB, CYS93ARG AND GLU121GLN
SNP: rs33972927, ClinVar: RCV000016317, RCV000016530, RCV000016617, RCV000016758, RCV000016858, RCV000029994, RCV000202465, RCV000723826, RCV000778329, RCV001175348, RCV002247348

See Wilson et al. (1991). This hemoglobin variant combines the mutations present in Hb D (glu121-to-gln; 141900.0065) and in Hb Okazaki (cys93-to-arg; 141900.0207).


.0408   HEMOGLOBIN GRENOBLE

HBB, PRO51SER AND ASP52ASN
SNP: rs281864894, rs33961886, gnomAD: rs281864894, rs33961886, ClinVar: RCV000016537, RCV000016759, RCV000029964, RCV001811161

See Lacombe et al. (1990). The asp52-to-asn mutation is also found in Hb Osu Christiansborg (141900.0212).


.0409   HEMOGLOBIN KODAIRA

HBB, HIS146GLN
SNP: rs33985739, ClinVar: RCV000016760

This abnormal hemoglobin was discovered in a 75-year-old Japanese male with an unusually low level of Hb A(1c) (Harano et al. (1990, 1992)). The patient was being treated for chronic renal failure. A CAC-to-CAA change in codon 146 was responsible for substitution of glutamine for histidine. Hb Kodaira was the fifth hemoglobin variant involving the terminal codon of the beta chain. The others are Hb Hiroshima (141900.0110), Hb York (141900.0305), Hb Cowtown (141900.0056), and Hb Cochin-Port Royal (141900.0051).


.0410   HEMOGLOBIN MONTREAL

HBB, 9-BP DEL AND 12-BP INS
ClinVar: RCV000016761

Plaseska et al. (1991) described a new variant with a beta chain 1 residue longer than the normal as a result of the deletion of asp, gly, and leu at positions 73, 74, and 75 and the insertion of ala, arg, cys, and gln in their place. Hb Montreal is unstable.


.0411   HEMOGLOBIN NIKOSIA

HBB, LYS17GLN
SNP: rs33986703, gnomAD: rs33986703, ClinVar: RCV000016762

See Spivak (1989).


.0412   HEMOGLOBIN ST. FRANCIS

HBB, GLU121GLY
SNP: rs33987957, gnomAD: rs33987957, ClinVar: RCV000016763

See Abourzik et al. (1991). This mutation is at the same nucleotide as that in Hb D (Los Angeles) (141900.0065).


.0413   HEMOGLOBIN YAHATA

HBB, CYS112TYR
SNP: rs33932908, ClinVar: RCV000016764

See Harano et al. (1991).


.0414   HEMOGLOBIN RANCHO MIRAGE

HBB, HIS143ASP
SNP: rs33929415, gnomAD: rs33929415, ClinVar: RCV000016765

A variant hemoglobin resulting from substitution of aspartic acid for histidine at residue 143 of the beta chain was detected in a 17-year-old male who had mild anemia (Moo-Penn et al., 1992).


.0415   BETA-ZERO-THALASSEMIA

HBB, GLU90TER
SNP: rs33913712, ClinVar: RCV000016766, RCV001078368, RCV003556031

In affected members in a Japanese family with beta-zero-thalassemia (613985), Hattori et al. (1992) found a GAG-to-TAG change in codon 90, substituting a stop codon for glutamic acid. The mutation had previously been found only in Japanese, the first case having been reported by Harano et al. (1989).


.0416   BETA-ZERO-THALASSEMIA

HBB, IVS2AS, -3, C-G
SNP: rs33913413, gnomAD: rs33913413, ClinVar: RCV000016767, RCV000759068, RCV001078322

Hattori et al. (1992) identified this mutation in a Japanese patient with beta-zero-thalassemia (613985). The abnormality was a substitution of guanine for cytosine at nucleotide 848 of IVS2. This nucleotide is at position -3 in the acceptor splice sequence. A C-to-A mutation at the same site in an Iranian patient had been reported by Wong et al. (1989); see 141900.0362.


.0417   BETA-PLUS-THALASSEMIA

HBB, 3-NT, 5-BP DEL, AATAAA-A
SNP: rs35949130, ClinVar: RCV000016768, RCV001078299

Rund et al. (1992) used a polyadenylation mutation involving the deletion of 5-bp (AATAAA-to-A) and another mutation (141900.0383) to study the function of the poly(A) signal in vivo and to evaluate the mechanism whereby polyadenylation mutations lead to a thalassemic phenotype.


.0418   BETA-ZERO-THALASSEMIA

HBB, IVS1AS, G-C, -1
SNP: rs33943001, gnomAD: rs33943001, ClinVar: RCV000016769, RCV000506434, RCV001078336, RCV001375484

In a Sicilian subject with beta-zero-thalassemia (613985), Renda et al. (1992) identified a G-C substitution in the invariant AG dinucleotide at the acceptor splice site of the first intron. In the same nucleotide, a G-A substitution is a frequent cause of beta-zero-thalassemia in Egyptians (see 141900.0356). Although mutations in the invariant GT or AG dinucleotide splice junctions are known to give rise to beta-zero-thalassemia, studies were not performed in the specific patient reported by Renda et al. (1992) to determine that this was in fact a beta-zero-thalassemia mutation.


.0419   BETA-ZERO-THALASSEMIA

HBB, 1-BP DEL, GTG-TG
SNP: rs63750475, gnomAD: rs63750475, ClinVar: RCV000016770, RCV001078428

In 3 out of 3,000 beta-thalassemia (613985) chromosomes in the Sardinian population, Rosatelli et al. (1992) found deletion of a single nucleotide G at codon 1 (GTG-to-TG), which resulted in both a frameshift and the formation of an in phase termination codon at codon 3. In addition, sequencing showed at codon 2 of the globin gene a single nucleotide substitution, C to T, which is a common silent substitution in the Mediterranean population (Orkin et al., 1982).


.0420   HEMOGLOBIN MUSCAT

HBB, LEU32VAL
SNP: rs33956555, rs34314652, gnomAD: rs33956555, ClinVar: RCV000016771

In 2 members of an Arabian family from Oman, Ramachandran et al. (1992) discovered a leu-to-val replacement at position beta-32 by reversed phase high performance liquid chromatography. In 1 person, it occurred with Hb S and in the other with Hb A. Although Hb Muscat was slightly unstable, its presence had no apparent adverse effect on the health of its carriers.


.0421   HEMOGLOBIN BAB-SAADOUN

HBB, LEU48PRO
SNP: rs33952850, ClinVar: RCV000016772

In a young Arabian boy living in Tunisia, Molchanova et al. (1992) detected a leu48-to-pro substitution in the beta chain. Since the parents did not have the variant, it presumably occurred by spontaneous mutation. It was thought not to be the cause of hemolytic anemia.


.0422   HEMOGLOBIN MANHATTAN

HBB, 1-BP DEL, -G, CODON 109
SNP: rs63751201, ClinVar: RCV000016687, RCV002284171

As alleles of the HBB gene producing beta-thalassemia were discovered, it became evident that there is a relative paucity of beta-thalassemia mutations in exon 3 of HBB even though this exon accounts for about 30% of the coding region. It appears to be a general rule that 1-bp frameshift mutations and nonsense mutations early in exon 3 produce a chronic hemolytic anemia in the heterozygous state. On the other hand, mutations of this type in exons 1 and 2 in the heterozygous state produce beta-thalassemia trait with mild phenotypic deviations from the normal. Kazazian et al. (1992) reported another example of this rule: in a 78-year-old Lithuanian Ashkenazi Jew with chronic hemolytic anemia, they demonstrated a -1 frameshift (-G) in codon 109. The globin was termed beta-Manhattan for the site of residence of the patient.


.0423   BETA-ZERO-THALASSEMIA

HBB, IVS2, G-C, -1
SNP: rs33952266, gnomAD: rs33952266, ClinVar: RCV000016774, RCV001078268, RCV001800306

In 4 members of a Yugoslavian family who exhibited severe microcytosis and hypochromic anemia (613985), Jankovic et al. (1992) found heterozygosity for a G-C mutation in the last nucleotide of IVS2. This change of the invariant AG dinucleotide of the acceptor splice site of intron 2 abolished normal splicing. Two other mutations of the IVS2 acceptor splice site have been identified as causes of beta-zero thalassemia; see 141900.0353 and 141900.0354.


.0424   BETA-THALASSEMIA INTERMEDIA

HEMOGLOBIN BRESCIA
HEMOGLOBIN DURHAM-N.C.
HBB, LEU114PRO
SNP: rs36015961, ClinVar: RCV000016775, RCV000016776, RCV000016777, RCV000759070, RCV001731305, RCV001826469

In a family of northern Italian descent (Brescia-Lombardia), Murru et al. (1992) found that a 14-year-old girl with the clinical phenotype of severe thalassemia intermedia (613985) had a heterozygous CTG-to-CCG change at codon 114 resulting in substitution of proline for leucine in the beta-globin chain. The resulting hemoglobin tetramer was highly unstable and precipitated to form inclusion bodies in peripheral red blood cells. The unusually severe phenotype present in this heterozygote was thought to be explained by the coinheritance of a triple alpha-globin locus.

In a 29-year-old female of Irish descent with thalassemia-like anemia during her first pregnancy, deCastro et al. (1992) found no gross structural alteration on Southern blot analysis of the globin genes but found an alpha:beta globin chain synthesis ratio of 0.91 (control = 0.94). Because they suspected an unstable hemoglobinopathy and because many of these disorders are due to point mutations in exon 3 of the beta-globin chain, they performed PCR-SSCP analysis, which showed an abnormality. Sequencing demonstrated a T-to-C transition at codon 114 resulting in a leucine-to-proline substitution. They called the hemoglobin variant Durham-N.C. to distinguish it from hemoglobin Durham, named for the city in England. The mutation created a novel MspI restriction site in exon 3 of the HBB gene. De Castro et al. (1994) demonstrated that this hemoglobinopathy, like several others within exon 3 of the beta-globin gene, e.g., Hb Showa-Yakushiji (leu110-to-pro; 141900.0262), result in a thalassemic and/or hemolytic phenotype with moderately severe microcytic anemia inherited as an autosomal dominant.

Kim et al. (2001) described the molecular and hematologic characteristics of a Korean family with a dominantly inherited beta-thalassemia. Carriers were characterized by moderate anemia, hypochromia, microcytosis, elevated Hb A2 and Hb F levels, and splenomegaly. A CTG (leu) to CCG (pro) change at codon 114 of the HBB was demonstrated. They referred to the abnormal hemoglobin as Hb Durham-N.C./Brescia.


.0425   BETA-PLUS-THALASSEMIA

HBB, -90C-T, PROMOTER
SNP: rs34999973, gnomAD: rs34999973, ClinVar: RCV000016778, RCV000029954, RCV000202364, RCV001069376, RCV002260510, RCV002288506

In an asymptomatic Portuguese female with beta-plua-thalassemia (613985), Faustino et al. (1992) found heterozygosity for a C-to-T transition at position -90 in the proximal CACCC box.


.0426   BETA-THALASSEMIA INTERMEDIA, DOMINANT

HBB, IVS2DS, 2-BP DEL, AG
SNP: rs34750035, ClinVar: RCV000016779, RCV001078289

In a Portuguese family with 'dominant' beta-thalassemia intermedia (613985), Faustino et al. (1992) found deletion of nucleotides 4 and 5 (AG) in IVS2 of the HBB gene, converting GTGAGT to GTGTCT.

In a 5-generation Portuguese family, Faustino et al. (1998) described an autosomal dominant form of beta-thalassemia intermedia. Carriers showed moderate anemia, hypochromia, microcytosis, elevated Hb A2 and Hb F, splenomegaly, hepatomegaly, and inclusion bodies in peripheral red blood cells after splenectomy. The molecular basis was found to be deletion of 2 nucleotides, AG, within the 5-prime splice site consensus sequence of intron 2 of the HBB gene. The fourth and fifth nucleotides in the sequence GTGAG were deleted. Reticulocyte RNA studies performed by RT-PCR and primary extension analysis showed 3 abnormally processed transcripts, which, upon sequencing, were shown to correspond to (1) skipping of exon 2, and (2) activation of 2 cryptic splice sites (between codons 59 and 60), and at nucleotide 47 in the second intron. In vitro translation studies showed that at least 1 of these aberrant mRNA species is translated into an abnormally elongated peptide whose cytotoxic properties could, in part, be causing the atypical dominant mode of inheritance observed in this family. Faustino et al. (1998) suggested that this elongated beta chain is unable to combine with an alpha-globin chain to form a functional hemoglobin molecule. Its degradation would, then, exhaust the proteolytic defense mechanism of the erythroid precursors, leading to inefficient proteolysis of the free alpha chains in excess.


.0427   HEMOGLOBIN DUINO

HBB, HIS92PRO AND ARG104SER
SNP: rs33914944, rs33974325, gnomAD: rs33914944, ClinVar: RCV000016293, RCV000016518, RCV000016780

Wajcman et al. (1992) demonstrated that Hb Duino, an unstable hemoglobin, carries 2 point mutations, the his92-to-pro mutation of Hb Newcastle (141900.0197) and the arg104-to-ser mutation of Hb Camperdown (141900.0042). Family studies demonstrated that the Hb Newcastle abnormality was a de novo mutation of a gene already carrying the Hb Camperdown substitution. One member of the Italian family studied by Wajcman et al. (1992) had hemolytic anemia.


.0428   HEMOGLOBIN BADEN

HBB, VAL18MET
SNP: rs35802118, ClinVar: RCV000016781

Divoky et al. (1992) analyzed the hemoglobin of a child of German descent living in the former German Democratic Republic and exhibiting typical clinical features of beta-thalassemia intermedia. One of his chromosomes 11 and 1 of his mother's carried a GTG-to-ATG mutation at codon 18, resulting in the replacement of a valine residue by a methionine residue. Called Hb Baden, the newly discovered beta-chain variant represented only 2 to 3% of the hemoglobin in both the patient and his mother because of the presence of an IVS1 +5 G-to-C thalassemic mutation (141900.0357) on the same chromosome. On the other chromosome, inherited from the father, the boy carried the val126-to-gly mutation of Hb Dhonburi (141900.0393), which itself is slightly unstable and associated with mild thalassemic features.


.0429   HEMOGLOBIN GRAZ

HBB, HIS2LEU
SNP: rs33983205, gnomAD: rs33983205, ClinVar: RCV000016782

Liu et al. (1992) accidentally detected 2 abnormal hemoglobins by cation exchange high performance liquid chromatography performed with an automated system designed to quantitate Hb A1c in blood samples from patients with diabetes mellitus. The variants eluted together with the fast-moving Hb A1c. One of the variants, found in 4 healthy, apparently unrelated adults, involved a change from a histidine to a leucine residue at position 2 of the beta chain. The second variant was identical to Hb Sherwood Forest (141900.0261).


.0430   BETA-ZERO-THALASSEMIA

HBB, MET1ILE
SNP: rs33930702, ClinVar: RCV000016783, RCV000506641, RCV000508308, RCV001078376, RCV002222353

In a typical beta-thalassemia (613985) carrier of Italian descent, Saba et al. (1992) demonstrated a G-to-A transition in the initiation codon of the HBB gene, producing a substitution of isoleucine for methionine. The absence of the initiation methionine led to defective beta-globin mRNA translation and probably determined the complete absence of beta-chain production. Indeed, initiation of translation may have occurred at the first downstream ATG sequence, which is located at codon 21-22; the resulting out-of-frame reading probably terminates at the new UGA termination codon at codon 60-61. Initiation codon mutations previously described in both the alpha (141850.0022) and beta (141900.0344) globin genes all result in complete inactivation of the affected globin gene.

In 7 members of 3 generations of a family living in northern Sweden, Landin et al. (1995) found an initiation codon mutation ATG-to-ATA of the HBB gene. The mutation changed the initiation codon from methionine to isoleucine and resulted in a beta-zero-thalassemic phenotype. The affected family members all presented hematologic findings typical for the beta-thalassemic trait, with slight anemia, marked microcytosis, and increased levels of Hb A2. See 141900.0345 for an initiation codon mutation ATG-to-ACG, which changes methionine to threonine.


.0431   HEMOGLOBIN KARLSKOGA

HBB, ASP21HIS
SNP: rs33950093, ClinVar: RCV000016784

In the course of quantification of Hb A(1c) in a 48-year-old Swedish woman, Landin (1993) discovered a variant hemoglobin that comprised approximately 39% of the total hemoglobin. A study demonstrated a GAT-to-CAT mutation in codon 21, corresponding to an asp21-to-his substitution. As predicted from the location of the substitution in the molecule, it was not associated with any overt hematologic abnormalities.


.0432   HEMOGLOBIN MUSKEGON

HBB, GLY83ARG
SNP: rs121909821, rs33930385, gnomAD: rs33930385, ClinVar: RCV000016785, RCV001283988

During a routine hematologic evaluation of a 1-year-old boy and his father, Broxson et al. (1993) found a variant hemoglobin that produced a band on electrophoresis in the same position as that for sickle hemoglobin. Screening of other family members showed that the paternal grandmother and an uncle also had the variant. Amino acid analysis demonstrated that glycine at position 83 of the beta-globin chain had been substituted by arginine. This gly83 is an external residue with no significant inter- or intra-molecular contacts, and mutation at this residue would not be expected to cause any changes in the functional properties of the variant.


.0433   HEMOGLOBIN TIGRAYE

HBB, ASP79HIS
SNP: rs33990858, ClinVar: RCV000016786, RCV001001454

In a healthy 36-year-old male of Ethiopian descent with normal hematologic findings, Molchanova et al. (1993) found a hemoglobin variant with electrophoretic mobility on cellulose acetate like that of Hb S. DNA studies demonstrated a GAC-to-CAC transversion leading to an asp79-to-his amino acid substitution.

Pistidda et al. (2001) identified the same mutation in a Caucasian in the Sassari district of Sardinia.


.0434   REMOVED FROM DATABASE


.0435   HEMOGLOBIN SARREBOURG

HBB, GLN131ARG
SNP: rs33950778, ClinVar: RCV000016787

Duwig et al. (1987) found a new unstable hemoglobin in a boy of 9 years hospitalized for hematuria and diffuse pains. Clinical examination demonstrated isolated splenomegaly without hepatomegaly or adenopathy. He was anemic and the variant hemoglobin constituted 30% of total hemoglobin. Molecular studies revealed a substitution of arginine for glutamine-131.


.0436   HEMOGLOBIN SAINT NAZAIRE

HBB, PHE103ILE
SNP: rs33921589, ClinVar: RCV000016788

In 4 apparently unrelated French families, Wajcman et al. (1993) found 5 patients carrying a hemoglobin variant associated with moderate erythrocytosis. The structural abnormality was a replacement of phenylalanine-103 by isoleucine. The residue involved was the same as that in Hb Heathrow (141900.0102), which is a phe103-to-leu substitution. The increase in oxygen affinity is much lower in Hb Saint Nazaire than in Hb Heathrow. The replacement of phenylalanine G5, which is located within the heme pocket, by leucine abolishes several contacts between heme and globin and leads to an environment of the heme with similarities to that observed in myoglobin. In contrast, the replacement of G5 by an isoleucine is likely to introduce less structural modifications.


.0437   HEMOGLOBIN HRADEC KRALOVE

HEMOGLOBIN HK
HBB, ALA115ASP
SNP: rs35485099, ClinVar: RCV000016791, RCV002284172

In a Czech family, Divoky et al. (1993) found a GCC-to-GAC mutation in codon 115 of the beta-globin gene as the cause of dominant beta-thalassemia trait. The variant hemoglobin was markedly unstable. A mother and daughter, who were heterozygotes, showed moderate anemia, reticulocytosis, nucleated red cells, target cells, Heinz body formation, and splenomegaly. Both had marked increase in fetal hemoglobin synthesis.


.0438   HEMOGLOBIN MANUKAU

HBB, VAL67GLY
SNP: rs33918343, ClinVar: RCV000016792, RCV002466407

Fay et al. (1993) described hemoglobin Manukau in 2 brothers presenting with nonspherocytic hemolytic anemia who became transfusion-dependent by 6 months of age. The severity of clinical expression seemed to be modulated by coexisting alpha-thalassemia. The brothers had a Niuean mother and a New Zealand Maori father. A second unusual feature was a modification of beta-141 leu, which appeared to be deleted because posttranslational modification had changed leu-141 to a residue (probably hydroxyleucine) that was not detected by standard amino acid analysis and sequencing methods. The same feature occurs in Hb Coventry (141900.0055).


.0439   HEMOGLOBIN VILLAVERDE

HBB, SER89THR
SNP: rs33917628, ClinVar: RCV000016793

In a 41-year-old man in Spain with severe erythrocytosis, Wajcman et al. (1993) found an electrophoretically silent hemoglobin variant with very high oxygen affinity and markedly reduced cooperativity. The structural abnormality was determined by mixing normal and abnormal beta chains, isolating the abnormal tryptic peptide by reversed-phase HPLC, and sequencing the peptide by mass spectrometry. Serine-89 was replaced by threonine.


.0440   HEMOGLOBIN HOWICK

HBB, TRP37GLY
SNP: rs33994623, ClinVar: RCV000016794

During routine hematologic investigation of a 44-year-old man, Owen et al. (1993) found a novel hemoglobin with high oxygen affinity and a substitution of glycine for tryptophan-37. This change would be expected to result in a destabilization of the deoxyhemoglobin form because of the reduced number of hydrogen bonds, salt bridges, and van der Waal contacts between the alpha-1 and beta-2 chains. Hemoglobin was 16.3 g/dL. The variant constituted 29% of the hemoglobin, indicating either reduced stability of the nascent Hb Howick chain or an impaired expression level.


.0441   HEMOGLOBIN DENVER

HBB, PHE41SER
SNP: rs33926796, ClinVar: RCV000016795, RCV000587370

Stabler et al. (1994) reported a 16-year-old white boy from Denver, Colorado, in whom cyanosis of the skin, lips, mucous membranes, conjunctivas, and nail beds was noted at the time of a dental extraction. The mother also had lifelong cyanosis and, although asymptomatic, had had severe anemia during pregnancy. The maternal grandmother and maternal aunt had chronic cyanosis and mild anemia. No abnormal hemoglobin band separate from that of hemoglobin A was found on electrophoresis, HPLC, and isoelectric focusing. However, a heat test showed hemoglobin instability, and O2 studies disclosed an appreciably right-shifted dissociation curve. On chromatography, the new variant--hemoglobin Denver--was found to carry a substitution of serine for phenylalanine at position 41 in the beta chain. In addition to reduction in O2 affinity, hemoglobin Denver was accompanied by moderate reticulocytosis and mild anemia. The corresponding substitution in the hemoglobin gamma gene is found in hemoglobin F (Cincinnati) (HBG2; 142250.0041) and is associated with cyanosis.


.0442   HEMOGLOBIN BECKMAN

HBB, ALA135GLU
SNP: rs35669628, gnomAD: rs35669628, ClinVar: RCV000016796

Rahbar et al. (1991) discovered Hb Beckman, an alanine-to-glutamic acid mutation at position 135 of the HBB gene, in a 32-year-old African American woman with chronic anemia and microcytosis and a palpable spleen. While substitution of proline at position 135 (Hb Altdorf; 141900.0007) results in an unstable hemoglobin variant with increased affinity for oxygen, substitution of glutamic acid has a reverse effect, i.e., Hb Beckman has reduced oxygen affinity.


.0443   HEMOGLOBIN KOREA

HBB, VAL33DEL OR VAL34DEL
SNP: rs35699671, ClinVar: RCV000016797

A de novo mutation was reported by Park et al. (1991) in an 8-year-old boy who presented with symptoms of mild anemia and was found to be icteric with moderate splenomegaly. PCR followed by DNA sequencing of the HBB gene demonstrated that the mutation results in a deletion of valine (GGT) at amino acid position 33 or 34 without altering the reading frame in the remainder of the subunit. The deletion appears to disrupt the globin structure badly, producing a clinical phenotype of beta-thalassaemia resembling that of an ineffective erythropoiesis.


.0444   MOVED TO 141900.0452


.0445   HEMOGLOBIN D (NEATH)

HBB, GLU121ALA
SNP: rs33987957, gnomAD: rs33987957, ClinVar: RCV000016799

During the course of a genetic survey of the first-year students at a London Medical School, Hb D (Neath) was discovered in an 18-year-old Caucasian female by Welch and Bateman (1993). In the variant HBB chain, the glutamic acid residue at position 121 is replaced with alanine.


.0446   HEMOGLOBIN WASHTENAW

HBB, VAL11PHE
SNP: rs33974228, gnomAD: rs33974228, ClinVar: RCV000016800, RCV000759071

Krishnan et al. (1993, 1994) reported a val-to-phe mutation at position 11 of the HBB chain in 6 members in 3 generations of a family of Hungarian-American descent. The proband had primary pulmonary hypertension, and other members of the family were mildly anemic. At least one other Hb variant, Hb Warsaw (141900.0257), has been reported to be associated with pulmonary hypertension. Hb Washtenaw is slightly unstable and has a low oxygen affinity.


.0447   HEMOGLOBIN ALESHA

HBB, VAL67MET
SNP: rs36008922, ClinVar: RCV000016276, RCV000016801

Molchanova et al. (1993) discovered Hb Alesha in a 15-year-old Russian patient with severe hemolytic disease, anemia, splenomegaly, Heinz body formation, and continued requirement for blood transfusions despite a splenectomy at age 3. PCR amplification and sequence analysis of the hemoglobin beta gene indicated a GTG-to-ATG point mutation at codon 67, causing a valine-to-methionine transition. Molchanova et al. (1993) postulated that the replacement of valine by the larger methionyl residue significantly reduces the stability of the hemoglobin molecule by disrupting the apolar bonds between the valine and the heme group.


.0448   HEMOGLOBIN DIEPPE

HBB, GLN127ARG
SNP: rs33910569, ClinVar: RCV000016802, RCV001078371

Girodon et al. (1992) reported Hb Dieppe in a 31-year-old French female with chronic anemia. DNA sequencing revealed a missense mutation (GAG-to-CGG) at position 127 of the beta-globin gene, causing a glutamine-to-arginine transition. The hemoglobin variant is highly unstable; the introduction of a positively charged hydrophilic residue at position 127 disrupts the tight contacts between the alpha and beta subunits.


.0449   HEMOGLOBIN HIGASHITOCHIGI

HEMOGLOBIN HT
HBB, GLY24DEL OR GLY25DEL
SNP: rs63749918, ClinVar: RCV000016803, RCV000016804

Hb Higashitochigi was discovered by Fujisawa et al. (1993) in a 2-year-old Japanese boy with chronic cyanosis. The variant is missing a glycine residue, due to a deletion of 3 nucleotides in the genomic DNA (codons 24-25: GGTGGT-to-GGT). It is likely that the absence of glycine indirectly distorts the heme pocket, causing decreased oxygen binding of the beta chain and impaired oxygen release of the normal alpha chain in the tetrameric molecule.


.0450   HEMOGLOBIN TROLLHAETTAN

HBB, VAL20GLU
SNP: rs33918474, ClinVar: RCV000016805

Landin et al. (1994) added another example to the more than 40 hemoglobin variants with increased oxygen affinity associated with erythrocytosis. In 3 generations of the family of a 23-year-old male from Trollhaettan in Sweden, Landin et al. (1994) observed heterozygosity for a GTG-to-GAG transition at codon 20 that predicted a val-to-glu substitution, which was confirmed at the protein level. The mutation occurred in the same codon as hemoglobin Olympia (141900.0210), which shows a val20-to-met amino acid substitution.


.0451   HEMOGLOBIN TYNE

HBB, PRO5SER
SNP: rs33912272, gnomAD: rs33912272, ClinVar: RCV000016806, RCV000756240, RCV001826470, RCV002271370

In a variant hemoglobin designated Hb Tyne, Langdown et al. (1994) observed a CCT-to-TCT change in codon 5 predicting substitution of serine for proline. The variant was first found in a 66-year-old diabetic male after an inappropriately low level of glycosylated hemoglobin was detected by enzyme immunoassay, and confirmatory ion exchange high performance liquid chromatography revealed the presence of an abnormal hemoglobin. Consequently, Langdown et al. (1994) identified the same mutation in an apparently unrelated diabetic male. Neither occurrence of the variant was associated with any abnormal hematologic findings.


.0452   HEMOGLOBIN MEDICINE LAKE

HBB, VAL98MET AND LEU32GLN
ClinVar: RCV000016443, RCV000016446, RCV000016807, RCV001811076, RCV001811157, RCV001826464

Coleman et al. (1993, 1995) investigated the molecular basis of transfusion-dependent hemolytic anemia in a Caucasian female infant who rapidly developed the phenotype of beta-thalassemia major. Both the father and mother were normal hematologically. The DNA sequence of one HBB allele demonstrated 2 mutations, one for the moderately unstable Hb Koln (141900.0151) and another for a novel leu32-to-gln change resulting from a CTG to CAG transversion. The new hemoglobin was called Hb Medicine Lake. The hydrophilic gln32 has an uncharged polar side chain that may distort the B helix and provoke further molecular instability. Biosynthesis studies of this mutation showed a deficit of beta-globin synthesis with early loss of beta-globin chains. Coleman et al. (1995) pointed to 14 previously described hemoglobin variants with 2 mutations in the same polypeptide chain. Most of these rare disorders had probably arisen via homologous crossing over. Such a mechanism, however, could not account for the Hb Medicine Lake, since neither parent had a detectable abnormal hemoglobin gene. Therefore, it was presumed that this was a true double de novo mutation.


.0453   HEMOGLOBIN YAIZU

HBB, ASP79ASN
SNP: rs33990858, ClinVar: RCV000016341, RCV000030906, RCV000507382

Harano et al. (1995) used the designation Hb Yaizu, after the city where the carrier lived, for a new beta-chain variant found in a Japanese female who was apparently healthy. Isoelectric focusing showed an abnormal hemoglobin band between the normal A2 and A bands. An asp79-to-asn amino acid substitution was demonstrated.


.0454   BETA-ZERO-THALASSEMIA

HBB, IVS2AS, G-A, -1
SNP: rs33952266, gnomAD: rs33952266, ClinVar: RCV000668023, RCV000736022, RCV001199849, RCV003558495

Curuk et al. (1995) described an American family of English-Scottish descent in which 6 members were found to be heterozygous for beta-thalassemia (613985). Sequencing of the HBB gene showed a G-to-A transition at the splice acceptor site of the second intron, changing the canonical AG to AA. Nucleotide 850 was involved; Curuk et al. (1995) commented that a G-to-C change in the same nucleotide had been found in a Yugoslavian family, whereas a frameshift due to deletion of nucleotide 850 was found in an Italian family. All 3 nucleotide changes lead to beta-zero thalassemia and are rare in the populations in which they were discovered.


.0455   HEMOGLOBIN HAKKARI

HBB, LEU31ARG
SNP: rs33920173, ClinVar: RCV000016810

Gurgey et al. (1995) observed a highly unstable hemoglobin variant in a 5-year-old Turkish girl with severe hemolytic anemia without Heinz body formation. A modest increase in liver and spleen size was present and level of Hb F was 33%. The variant could not be observed in red cells and was only detected through sequencing of the amplified beta-globin gene and also by hybridization with specific oligonucleotide probes. The variant was presumably a de novo mutation, since the parents were normal. Smears from bone marrow aspirates showed numerous inclusion bodies in erythroblasts and, as a result, erythroid hyperplasia. It was suggested that this hemoglobin variant was unstable and readily lost its heme group because one of the heme-binding sites had been lost and that, as a result, it precipitates in erythroblasts, thus interfering with the maturation process and causing severe anemia.


.0456   MOVED TO 141900.0430


.0457   HEMOGLOBIN PUTTELANGE

HBB, ALA140VAL
SNP: rs33927093, ClinVar: RCV000016811, RCV003234910

In 2 sibs with polycythemia in a French family, Wajcman et al. (1995) found a de novo ala140-to-val mutation. The hemoglobin displayed increased oxygen affinity, thus explaining the polycythemia. Both parents were phenotypically normal and study of polymorphic markers from several chromosomes were consistent with paternity. Since 2 brothers were affected, it was considered likely that the mutation had occurred in the germline of the father.


.0458   HEMOGLOBIN ARTA

HBB, PHE45CYS
SNP: rs33978338, ClinVar: RCV000016812

In a 22-year-old Caucasian female, known to be anemic from early childhood and showing scleral subicterus and slightly enlarged spleen on physical examination, Vassilopoulos et al. (1995) described a new unstable hemoglobin variant with reduced oxygen affinity. A phe45-to-cys amino acid substitution was found in beta-globin. The other chromosome 11 carried the gln39-to-ter (141900.0312) mutation that causes beta-zero-thalassemia. The new variant was named for the Greek city where the patient was born.


.0459   HEMOGLOBIN AURORA

HBB, ASN139TYR
SNP: rs33910475, ClinVar: RCV000016813

In a 73-year-old female of Dutch descent, Lafferty et al. (1995) found that a high oxygen affinity hemoglobin variant resulted from an AAT-to-TAT transversion of codon 139, resulting in an asn139-to-tyr amino acid substitution. See 141900.0092 for the asn139-to-asp mutation and 141900.0108 for the asn139-to-lys mutation involving the same codon.


.0460   HEMOGLOBIN NAKANO

HBB, LYS8MET
SNP: rs33932981, ClinVar: RCV000016814

During the assay of glycated hemoglobin by HPLC, Harano et al. (1995) identified a new hemoglobin named Hb Nakano for the district of Tokyo where healthy, 46-year-old Japanese woman lived and showed that it was due to a change of codon 8 from lysine to methionine. See 141900.0135 for the lys8-to-gln mutation, 141900.0191 for the lys8-to-glu mutation, and 141900.0237 for the lys8-to-thr mutation.


.0461   HEMOGLOBIN HINWIL

HBB, THR38ASN
SNP: rs34703513, ClinVar: RCV000016815

Frischknecht et al. (1996) found a new hemoglobin variant in the course of investigation of mild erythrocytosis. Mutation mapping of the beta-globin gene by PCR and denaturing gradient gel electrophoresis (DGGE) followed by sequence analysis revealed a C-to-A transversion at codon 38, predicting a thr38-to-asn substitution. In contrast to the other known mutation at codon 38, thr38-to-pro (known as Hb Hazebrouck; 141900.0101), Hb Hinwil was found to be stable and showed elevated oxygen affinity.


.0462   HEMOGLOBIN DEBROUSSE

HBB, LEU96PRO
SNP: rs36081208, ClinVar: RCV000016816

Lacan et al. (1996) described an unstable variant hemoglobin with high oxygen affinity responsible, in the steady state, for an apparently well-compensated chronic hemolytic anemia. The defect was shown to be a leu96-to-pro substitution in the HBB gene. The hemoglobin was named for the hospital in Lyon, France where the patient was observed. This electrophoretically neutral hemoglobin was found as a de novo case in a 6-year-old girl suffering from severe anemia with hemolysis and transient aplastic crisis following infection by parvovirus B19.


.0463   BETA-THALASSEMIA

HBB, 2-BP DEL, CC, CODONS 38-39
SNP: rs267607291, gnomAD: rs267607291, ClinVar: RCV000016817

In 3 members of an indigenous Belgian family with beta-thalassemia (613985), Heusterspreute et al. (1996) found a deletion of 2 nucleotides, CC, from codons 38 and 39. The mutation eliminates an AvaII restriction site and so can be routinely investigated by AvaII digestion of amplified DNA.


.0464   HEMOGLOBIN TSURUMAI

HBB, LYS82GLN
SNP: rs33940051, ClinVar: RCV000016818

In a 46-year-old Japanese male with plethora and erythrocytosis, Ohba et al. (1996) found a lys82gln amino acid substitution in the beta-globin chain. A son also had erythremia due to this hemoglobin variant.


.0465   HEMOGLOBIN J (EUROPA)

HBB, ALA62ASP
SNP: rs34151786, gnomAD: rs34151786, ClinVar: RCV000016819

In a 27-year-old man of Italian origin living in Belgium investigated because of mild polycythemia with microcytosis, Kiger et al. (1996) found that the hemoglobin had a negatively charged residue near the distal histidine and an ala62-to-asp substitution. The variant was called Hb J-Europa, presumably because it was found in the proband during a systematic physical examination performed before employment at the headquarters of the European Economic Community (EEC) in Luxembourg.


.0466   HB AUBENAS

HBB, GLU26GLY
SNP: rs33915112, ClinVar: RCV000016820

Lacan et al. (1996) found this mildly unstable variant in a French family without hematologic or clinical features. Although the substitution involves the same residue as in Hb E (141900.0071), the new sequence in this case did not create an additional out-of-frame splice site. The mutated chain was, therefore, normally synthesized.


.0467   HB CAMPERDOWN

HBB, ARG104SER
SNP: rs33914944, gnomAD: rs33914944, ClinVar: RCV000016789, RCV000508224

Miranda et al. (1996) described Hb Camperdown in a 24-year-old Brazilian woman of Italian origin. Although carriers do not show significant clinical alterations, Hb Camperdown is considered an unstable Hb.


.0468   BETA-THALASSEMIA, DOMINANT

HBB, 3-BP INS, CGG, CODON 30
SNP: rs35348864, ClinVar: RCV001078385, RCV001732037

Negri Arjona et al. (1996) described a Spanish family with a dominant type of beta-thalassemia (613985). Carriers were characterized by mild anemia, hyperchromia, microcytosis, elevated Hb A2 and Hb F levels, reticulocytosis, and splenomegaly. They found that the molecular basis was the introduction of a CGG triplet between codons 30 and 31 of the HBB gene; this was determined by sequencing of amplified DNA and confirmed by dot-blot analysis. The abnormal mRNA was stable and present in quantities similar to that of normal mRNA. The abnormal mRNA translated into a beta-chain that was 147 amino acid residues long and carried an extra arginine residue between residues 30 and 31. The abnormal beta chain may be unstable and does not bind to the alpha-chain. It probably is continuously digested by proteolytic enzymes in red cell precursors in the bone marrow. The abnormal chain probably binds haem that is excreted after proteolysis causing a darkening of urine, which was a clinical characteristic of the disorder. The insertion occurred at the 3-prime end of IVS1 and the 5-prime end of exon 2. The insertion may have an addition of CGG between codons 30 and 31 or an insertion of GGC between IVS1 129/130.


.0469   HEMOGLOBIN COSTA RICA

HBB, HIS77ARG
SNP: rs33952543, ClinVar: RCV000016822

Rodriguez Romero et al. (1996) discovered an abnormal beta-chain hemoglobin Hb Costa Rica, or beta-his77arg, in a healthy young Costa Rican female. This stable hemoglobin, termed Hb Costa Rica, was present in only 6 to 8% of hemoglobin and was not observed in any relative (the father was not available for study). The expected CAC-to-CGC mutation could not be detected in genomic DNA. Smetanina et al. (1996) presented convincing evidence that the CAG-to-CGC mutation at codon 77 of the HBB gene had occurred as a somatic mutation during embryonic development and resulted in mosaicism with only 6 to 8% of the abnormal Hb Costa Rica in circulating red cells. Bradley et al. (1980) had described an instance of gonadal mosaicism accounting for an unusual pedigree pattern in a family with Hb Koln (141900.0151). Smetanina et al. (1996) incorrectly stated that theirs was the first example of mosaicism in a hematopoietic system.


.0470   BETA-THALASSEMIA, ASHKENAZI JEWISH TYPE

HBB, 1-BP INS, CODON 20/21, FS
SNP: rs1554918165, ClinVar: RCV000666440, RCV002284203

Beta-thalassemia (613985) alleles are uncommon among Ashkenazi Jews as compared with Sephardic Jews and other populations. Oppenheim et al. (1993) described a rare allele, a single-base insertion resulting in a frameshift at codon 20/21, in an Ashkenazi Jewish proband with beta-thalassemia (613985) living in Israel. Martino et al. (1997) independently discovered this allele (called fs20/21 by them) in a Montreal Ashkenazi pedigree and investigated the possibility of genealogic connections between the 2 families. They showed by analysis of the mutation and the associated marker haplotype that the Israeli and Montreal probands appeared to be identical by descent and certainly had identity by state at the HBB locus. Genealogic reconstruction suggested that the 2 families had a shared origin in time and space.


.0471   HB NIIGATA

HBB, VAL1LEU
SNP: rs33958358, gnomAD: rs33958358, ClinVar: RCV000016824

Ohba et al. (1997) reported the fifth variant with retention of the initiator methionine and partial acetylation. The proband, a 37-year-old Japanese male, was subjected to detailed studies because of an unexpectedly high HbA1c value on cation exchange high performance liquid chromatography. The findings of their subsequent studies, as well as previous reports, suggested that retention of the initiator methionine and acetylation have no physiologic or pathologic significance, at least on human hemoglobin. The authors found that the variant hemoglobins were not unstable in in vitro tests. Ohba et al. (1997) stated that they must be almost as stable as normal HbA in vivo because they comprise over 40% of total Hb in the peripheral blood. The 4 previously reported Hb variants with retention of initiator methionine were Hb Thionville (141800.0168), Hb Marseille (141900.0171), Hb Doha (141900.0069), and Hb South Florida (141900.0266).

This variant was numbered based on the first amino acid of the mature protein. In the gene-based system of counting, this variant is VAL2LEU.


.0472   BETA-ZERO-THALASSEMIA

HBB, 5-BP DEL AND 1-BP INS
SNP: rs63751218, ClinVar: RCV000016826, RCV001078313

Waye et al. (1997) described a beta-thalassemia (613985) trait in a Caucasian woman of British descent living in Ontario, Canada. The 48-year-old woman presented with typical high Hb A2 beta-thalassemia trait. All known family members were of British ancestry. Her father had normal hematologic indices and her mother was deceased. There was no family history of anemia. Direct nucleotide sequencing demonstrated a complex frameshift mutation due to deletion of 5 nucleotides (AGTGA) and insertion of 1 nucleotide (T) at codons 72/73 of the HBB gene. This introduced a premature stop codon (TGA) at codon 88, resulting in beta-zero-thalassemia.


.0473   HB GAMBARA

HBB, LYS82GLU
SNP: rs33940051, ClinVar: RCV000016827

In a Lombardy family (from Gambara, near Brescia in Northern Italy), Ivaldi et al. (1997) described a 45-year-old man and his 2 daughters who carried an abnormal hemoglobin resulting in modest erythrocytosis and mild, compensated hemolysis with slight splenomegaly. The abnormal hemoglobin represented about 52% of the total hemoglobin, and was shown to be stable by the isopropanol test. Sequencing demonstrated a change in the HBB gene of codon 82 from AAG (lys) to GAG (glu) in heterozygous state.


.0474   BETA-ZERO-THALASSEMIA

HBB, IVS1AS, A-G, -2
SNP: rs63750513, gnomAD: rs63750513, ClinVar: RCV000016828, RCV000988481, RCV003476900

Waye et al. (1998) studied the hemoglobin of a 37-year-old woman who presented during pregnancy with the beta-thalassemia (613985) trait. The father and mother were Sephardic Jews whose families had lived for many generations in Tangiers and Gibraltar, respectively. The HBB gene was found to have a single basepair substitution at codon 30: AGG (arg) to GGG (gly). The mutation changed the sequence immediately upstream of the 5-prime splice junction of the first intron: A-to-G at position -2 of IVS1. The authors stated that although mutations had been found at positions -1 and -3 of IVS1, no mutation had been described at the -2 position. The authors thought it unlikely that an arg30-to-gly substitution was responsible for the abnormality and favored the possibility that the mutation impaired the normal splicing of the beta-globin pre-mRNA.

Li et al. (1998) identified the same mutation in a Chinese man whose wife carried the 4-bp deletion at codons 41/42 (141900.0326) that is a common beta-thal mutation in Japanese. Their son had died of severe anemia at age 4 and the authors speculated that he had beta-0-thalassemia due to compound heterozygosity for these mutations.


.0475   BETA-ZERO-THALASSEMIA

HBB, 1-BP INS, T, CODON 26
SNP: rs35477349, ClinVar: RCV000016829, RCV001078437

Hattori et al. (1998) identified a new beta-thalassemia (613985) allele in a 31-year-old Japanese man who was found to have microcytosis and erythrocytosis during a health check-up. His red blood cell count was 6.53 x 10(12) per liter. The HBB gene in 1 allele was found to have an insertion of T at codon 26: GAG-to-GTAG. The frameshift mutation was expected to result in beta-zero-thalassemia because the translation of the abnormal mRNA produced a peptide with an abnormal amino acid sequence from codon 26 to 42 where it terminates. Such a truncated peptide of 42 residues would be immediately eliminated by proteolysis. Codon 26 is involved in the consensus sequence for cryptic splicing at codon 25. The insertion of T at codon 26 breaks the consensus sequence and is unlikely to affect the alternative splicing. Results of SSCP analysis indicated that the patient was heterozygous for the frameshift.


.0476   HEMOGLOBIN SILVER SPRINGS

HBB, GLN131HIS
SNP: rs34188626, ClinVar: RCV000016830

Hoyer et al. (1998) described a new hemoglobin variant called Hb Silver Springs which resulted from a CAG (gln)-to-CAC (his) change at codon 131 of the beta chain. It was detected only by cationic exchange high performance liquid chromatography. This was the fifth reported substitution at codon 131. The variant did not appear to have any clinical or hematologic manifestations. It was found in 6 African Americans from 4 presumably unrelated families.


.0477   HEMOGLOBIN BURTON-UPON-TRENT

HEMOGLOBIN OLD DOMINION
HBB, HIS143TYR
SNP: rs33929415, gnomAD: rs33929415, ClinVar: RCV000016831, RCV001811165

In investigating the nature of the unique hemoglobin variant that caused a spurious increase in glycated hemoglobin, Hb A(1c), Elder et al. (1998) found a CAC-to-TAC mutation in the HBB gene that resulted in a his143-to-tyr substitution in the beta-globin peptide. This amino acid substitution affected an important 2,3-diphosphoglycerate binding site and slightly increased the oxygen affinity of the hemoglobin variant. Despite the slight increase in oxygen affinity, the mutation was without hematologic effect, and its only clinical significance was that it coeluted with Hb A(1c) on ion-exchange chromatography and compromised the use of this analyte to monitor the treatment of diabetes mellitus. The variant was encountered in 4 unrelated persons of Irish or Scottish-Irish ancestry.

Gilbert et al. (2000) reported 2 unrelated cases of Hb Old Dominion/Burton-upon-Trent.

Plaseska-Karanfilska et al. (2000) found the same mutant hemoglobin in a 72-year-old Korean woman with type II diabetes (125853).


.0478   HEMOGLOBIN RIO CLARO

HBB, VAL34MET
SNP: rs1141370, ClinVar: RCV000016833, RCV000781454

By globin chain electrophoresis, Grignoli et al. (1999) detected a novel silent hemoglobin variant in a 4-year-old Caucasian Brazilian boy of Italian descent, and in his mother. Sequencing of the HBB gene revealed a G-to-A transition at the first position of codon 34, resulting in a val-to-met substitution. In the boy, this variant was found to be associated with Hb Hasharon (141850.0012) and alpha-thalassemia-2 (rightward deletion).


.0479   HEMOGLOBIN NIJKERK

HBB, 4-BP DEL/1-BP INS, CODONS 138/139, GCTA/T
SNP: rs34359964, ClinVar: RCV000016834, RCV000132763

Van den Berg et al. (1999) identified a novel Hb B variant, termed Hb Nijkerk, in a Caucasian Dutch girl who was slightly icteric at birth and developed hemolytic anemia and hepatosplenomegaly at about 5 months of age. Red cell transfusions were necessary every 3 to 4 weeks. Erythromorphology was markedly abnormal, with large numbers of red cells with inclusion bodies. Splenectomy was performed at the age of 18 months, after which the need for transfusions decreased and they were finally discontinued. Although still anemic, the child's growth was otherwise normal. Repeated hemoglobin electrophoresis on cellulose acetate revealed no abnormalities. At the age of 17 years, a minor abnormal band, migrating slightly faster than Hb A2, was detected on starch gel electrophoresis. Sequencing of the HBB gene revealed heterozygosity for a 4-bp deletion (GCTA) in combination with a 1-bp insertion (T) at codons 138/139. This event eliminated 2 amino acids (ala and asn) and introduced a new residue (tyr) into the protein. The parents did not carry the mutation and paternity analysis showed no discrepancies, indicating that Hb Nijkerk should be considered as a de novo event.


.0480   HEMOGLOBIN CHILE

HBB, LEU28MET
SNP: rs33958088, gnomAD: rs33958088, ClinVar: RCV000016835

Hojas-Bernal et al. (1999) identified a novel Hb B gene variant, termed Hb Chile, in a 57-year-old Native American living in Chile who was known to be chronically cyanotic. He was hospitalized for elective surgery of left pyeloureteral stenosis. Prior to surgery, he was given sulfonamides. Surgery was terminated when the dark color of his blood was noted. Arterial oxygen saturation was 80%. His blood contained 18% methemoglobin. Repeated intravenous methylene blue was given for the methemoglobinemia but to no avail. Sulfhemoglobin was not increased. Subsequently, an acute episode of hemolytic anemia occurred. Red cell glucose-6-phosphate dehydrogenase and methemoglobin reductase were normal. The patient's father and 1 of his 2 children also showed cyanosis. Tryptic digestion of the beta-globin chain and subsequent chromatography revealed an abnormal beta-T-3 peptide; sequencing revealed a leu-to-met substitution at position 28, predicted to be caused by a CTG-to-ATG transversion in the HBB gene. Hojas-Bernal et al. (1999) concluded that Hb Chile is an unstable hemoglobin that forms methemoglobin in vivo spontaneously at an accelerated rate and predisposes to drug-induced hemolytic anemia.


.0481   HEMOGLOBIN TENDE

HBB, PRO124LEU
SNP: rs33983276, ClinVar: RCV000016836, RCV000759073, RCV001000143

By chromatographic measurement of glycated Hb in a 90-year-old woman of French origin, Wajcman et al. (1998) identified a novel hemoglobin variant, termed Hb Tende, that showed a moderate increase in oxygen affinity. Sequencing of the HBB gene revealed a CCA-to-CTA transition, resulting in a pro124-to-leu substitution. Three hemoglobin variants at amino acid 124 had been previously described: Hb Tunis (pro124 to ser; 141900.0288) is asymptomatic; Hb Khartoum (pro124 to arg; 141900.0148) is mildly unstable; and Hb Ty Gard (pro124 to gln; 141900.0289) is responsible for increased oxygen affinity leading to erythrocytosis. Wajcman et al. (1998) suggested that the absence of erythrocytosis in the Hb Tende carrier whom they studied was likely due to the relatively low proportion of abnormal Hb (34%), possibly explained by the mild instability revealed by the isopropanol test, and to the normal cooperativity of the variant.


.0482   HEMOGLOBIN LA ROCHE-SUR-YON

HBB, LEU81HIS
SNP: rs33936967, ClinVar: RCV000016837

Wajcman et al. (1992) identified Hb La Roche-sur-Yon, an unstable hemoglobin variant resulting from a leu81-to-his substitution in the HBB gene. The variant displayed a moderately increased oxygen affinity. in addition to the substitution at beta-81, about half the abnormal hemoglobin carried a deamidation of the neighboring asparagine residue at beta-80. The authors concluded that the deamidation depends not only on the flexibility of the polypeptide region but also on the presence of a neighboring histidine residue to catalyze the reaction. See also Hb Redondo (141900.0404).


.0483   HEMOGLOBIN IRAQ-HALABJA

HBB, ALA10VAL
SNP: rs33947457, ClinVar: RCV000016838

In a family originating from Iraq, Deutsch et al. (1999) identified a novel beta-chain silent variant, a change of codon 10 from GCC to GTC (ala10 to val), in association with thalassemia. The variant, which they designated Hb Iraq-Halabja, gave a normal oxygenation curve, a normal heterotopic action of 2,3-DPG, and normal heat stability and isopropanol precipitation tests. The variant showed a clear difference in migration properties compared to normal beta chain only when run on PAGE urea Triton. The codon involved in Hb Iraq-Halabja is the same as that mutant in Hb Ankara (141900.0009), in which the substitution is ala10 to asp.


.0484   HEMOGLOBIN LUCKNOW

HBB, LYS8ARG
SNP: rs33932981, ClinVar: RCV000016839

Agarwal et al. (1999) found an A-to-G transition in exon 1 of the HBB gene at codon 8 which resulted in a lys8-to-arg amino acid substitution. This change was associated with a splice mutation and was speculated to produce a thalassemia intermedia phenotype in the subject.


.0485   HEMOGLOBIN SAGAMI

HBB, ASN139THR
SNP: rs34407387, ClinVar: RCV000016840

Miyazaki et al. (1999) described compound heterozygosity for a beta(+)-thalassemia mutation and a new beta variant with low oxygen affinity, Hb Sagami (asn139 to thr).


.0486   HEMOGLOBIN HARROW

HBB, PHE118CYS
SNP: rs33928092, ClinVar: RCV000016841

Henthorn et al. (1999) reported a new beta-globin variant, phe118 to cys, found in a newborn male of Indian Gujerati origin, living in the Harrow area of London, England. This variant was observed during a systematic program of neonatal screening. The mother also carried the abnormal hemoglobin.


.0487   HEMOGLOBIN BRIE COMTE ROBERT

HBB, PRO36ALA
SNP: rs33948615, gnomAD: rs33948615, ClinVar: RCV000016842

Wajcman et al. (1999) described a beta-globin variant in a 36-year-old French Caucasian male who presented with polycythemia. The variant was named Hb Brie Comte Robert for the place where the carrier resided. It was shown to have high oxygen affinity.


.0488   HEMOGLOBIN BARBIZON

HBB, LYS144MET
SNP: rs33996892, ClinVar: RCV000016843

In several members of a French family, Kister et al. (1999) identified a lys144-to-met mutation in the HBB gene. The mutation is a clinically silent variant in which the structural modification disturbs the oxygen-linked chloride binding.


.0489   HEMOGLOBIN BOLOGNA-ST. ORSOLA

HBB, HIS146TYR
SNP: rs33961444, ClinVar: RCV000016844

In 3 members of a family from Bologna, Italy, Ivaldi et al. (1999) demonstrated that erythrocytosis was the result of a variant beta-globin chain, a CAC-to-TAC mutation in codon 146 leading to a his146-to-tyr amino acid substitution. Ivaldi et al. (1999) pointed out that this was the sixth substitution that had been identified in the C-terminal residue of the beta-globin chain, the others being his146-to-asp (141900.0110), his146-to-pro (141900.0305), his146-to-leu (141900.0056), his146-to-arg (141900.0051), and his146-to-gln (141900.0409).

Gilbert et al. (2000) described a second case of Hb Bologna-St. Orsola in a family of Anglo-Celtic origin.


.0490   HEMOGLOBIN VILA REAL

HBB, PRO36HIS
SNP: rs33993004, ClinVar: RCV000016845, RCV001029750, RCV003886362

In a 15-year-old Portuguese girl with erythrocytosis, Bento et al. (2000) found a new high oxygen affinity variant called Hb Vila Real and characterized by a pro36-to-his (P36H) missense mutation of the HBB gene. The patient's mother had undergone regular phlebotomies over the previous 20 years for polycythemia, with an obstetric history of 2 miscarriages, a stillborn baby, and 2 normal children by elective Cesarean section. A transversion converted codon 36 from CCT to CAT. The variant was named after the city in Portugal where the carrier was born.

Salzano et al. (2002) reported the same rare high oxygen affinity hemoglobin variant in a 22-year-old male patient from Naples, Italy, affected by erythrocytosis. The DNA mutation was identified as a change in codon 36 of the HBB gene from CCT to CAT. The father carried the same hemoglobin variant in heterozygous state.


.0491   HEMOGLOBIN SAALE

HBB, THR84ALA
SNP: rs35960772, ClinVar: RCV000016846, RCV000759063

In a 3-year-old anemic German girl, Bisse et al. (2000) detected an abnormal hemoglobin by cation-exchange high performance liquid chromatography. Further studies characterized the variant as a thr84-to-ala replacement in the HBB gene, which the authors named Hb Saale for the river crossing the city in which the proband lived. Hb Saale could be not be separated by electrophoresis or isoelectric focusing. It was found to be slightly unstable, exhibiting a moderate tendency to autooxidize. Functional properties and the heterotropic interactions were similar to those of hemoglobin A.


.0492   HEMOGLOBIN BUSHEY

HBB, PHE122LEU
SNP: rs33971848, rs33973589, ClinVar: RCV000016847, RCV000016848

Wajcman et al. (2000) found a hemoglobin variant, designated Hb Bushey, in a Chinese baby and his father. The variant was found to be caused by a point mutation leading to a phe122-to-leu substitution in the HBB gene. The same amino acid substitution was found in Hb Casablanca (141900.0493), in combination with another abnormality in the HBB gene, i.e., a lys65-to-met amino acid substitution (Hb J (Antakya); 141900.0121).


.0493   HEMOGLOBIN CASABLANCA

HBB, LYS65MET AND PHE122LEU
SNP: rs33932548, rs33971848, rs33973589, ClinVar: RCV000016398, RCV000016847, RCV000016848

Wajcman et al. (2000) found a hemoglobin variant in a family in Morocco and designated it Hb Casablanca. It was found to be another example of a hemoglobin variant with 2 abnormalities in the same chain: the first was identical to that of Hb Bushey (phe122 to leu; 141900.0492) and the second to that of Hb J (Antakya) (lys65 to met; 141900.0121). The stability and oxygen-binding properties of Hb Bushey and Hb Casablanca were identical to those of Hb A.


.0494   HEMOGLOBIN TSUKUMI

HBB, HIS117TYR
SNP: rs33935527, rs34049764, ClinVar: RCV000016849

Oribe et al. (2000) found a new hemoglobin variant in a Japanese male: a change at codon 117 of the HBB gene from CAC (his) to TAC (tyr). The authors designated this variant Hb Tsukumi after the patient's place of residence. Two other hemoglobin variants have a change in his117: a change to arg in the case of Hb P (Galveston) (141900.0213), and a change to pro in the case of Hb Saitama (141900.0250).

North et al. (2001) found Hb Tsukumi in a Moroccan woman.


.0495   HEMOGLOBIN ERNZ

HBB, THR123ASN
SNP: rs33935383, gnomAD: rs33935383, ClinVar: RCV000016851, RCV001563767, RCV001778656, RCV002482877

Analysis of globin chains by reversed phase high performance liquid chromatography, used as an additional tool for characterizing hemoglobin variants, led to the discovery of a new class of variants that display only differences in hydrophobicity. Groff et al. (2000) described 2 such variants: Hb Ernz and Hb Renert (141900.0496). Hb Ernz, a thr123-to-asn substitution, was found in a man of Italian origin who was polycythemic and in 2 of his 3 daughters who were hematologically normal. See 141900.0294 for a thr123-to-ile substitution.


.0496   HEMOGLOBIN RENERT

HBB, VAL133ALA
SNP: rs35825479, ClinVar: RCV000016852

Groff et al. (2000) identified Hb Renert, a val133-to-ala substitution in the HBB gene, in a man from Cape Verde who also carried Hb S (141900.0243) and presented with chronic hemolysis.

Wilson et al. (2001) described a second case of Hb Renert. They commented that this was only the second hemoglobin variant involving beta-133, the other being Hb Extremadura (V1133L; 141900.0074).


.0497   HEMOGLOBIN WATFORD

HBB, VAL1GLY
SNP: rs121909815, rs33949930, gnomAD: rs33949930, ClinVar: RCV000016854

Four hemoglobin variants had previously been described that involve the first codon of the HBB gene: Hb Doha (141900.0069), Hb South Florida (141900.0266), Hb Niigata (141900.0471), and Hb Raleigh (141900.0233). Although none of these variants cause any significant clinical problems, mutations of the first codon are of interest because of their potential interference with cotranslational modification at this site during beta-globin synthesis. In eukaryotes, the translation of all peptide mRNAs starts at an AUG codon, producing methionine at the beginning of the nascent peptide chain. In most proteins, including alpha-, beta-, and gamma-globin, this methionine is cotranslationally cleaved when the chain is 20 to 30 amino acids long. This results in the first amino acid being valine in alpha-, beta-, and delta-globin, and glycine in gamma-globin. When the peptide chain is 40 to 50 amino acids long, further modification occurs with acetylation at the NH2-terminal residue. The extent of the acetylation depends on the identity of the N-terminal amino acid; valine is strongly inhibitory to this process, leading to little acetylation of alpha- and beta-globin. However, the N-terminal glycine of gamma-globin is less inhibitory, resulting in about 15% acetylation. Fisher et al. (2000) identified a new Hb variant, Hb Watford, in which a GTG-to-GGG substitution caused a change of the first amino acid of the beta-globin chain from methionine to glycine, mimicking the gamma-globin chain. The proband was a 48-year-old female of Jewish extraction who was evaluated for chronic mild anemia. Another mutation was found in cis with the val1-to-gly mutation: Cap+36G-A.


.0498   HEMOGLOBIN YAOUNDE

HBB, VAL134ALA
SNP: rs33966761, gnomAD: rs33966761, ClinVar: RCV000016855, RCV000588829, RCV000855596, RCV001835629

Yapo et al. (2001) described a val134-to-ala missense mutation of the HBB gene in a 45-year-old man originating from Cameroon, a migrant worker in France. He was a compound heterozygote for this mutation, designated Hb Yaounde, and for Hb Kenitra (141900.0147). Hb Kenitra had previously been described only in persons of Moroccan origin. Hb Yaounde appeared to be neutral; Hb Kenitra is associated with expression at a level slightly higher than that of Hb A.

Faustino et al. (2004) described Hb Yaounde in a 3-generation Portuguese family. The proband had compound heterozygosity for this hemoglobin variant and for hemoglobin C (glu6 to lys; 141900.0038). Hb Yaounde was associated with the Mediterranean haplotype II, supporting the hypothesis of a genetic origin independent of the African origin.


.0499   HEMOGLOBIN SITIA

HBB, ALA128VAL
SNP: rs33957286, ClinVar: RCV000016850, RCV003230367

Papassotiriou et al. (2001) identified hemoglobin Sitia, an ala128-to-val missense mutation in the HBB gene, in a Greek female with slightly reduced red blood cell indices.


.0500   HEMOGLOBIN MONT SAINT-AIGNAN

HBB, ALA128PRO
SNP: rs34139813, gnomAD: rs34139813, ClinVar: RCV000016856

In a 33-year-old French Caucasian woman displaying a well-tolerated chronic anemia, Wajcman et al. (2001) found Hb Mont Saint-Aignan, a mildly unstable variant associated with hemolytic anemia, marked microcytosis, and increased alpha/beta biosynthetic ratio. The molecular defect was an ala128-to-pro missense mutation of the HBB gene.


.0501   HEMOGLOBIN 'T LANGE LAND

HBB, GLY136ARG
SNP: rs33984863, ClinVar: RCV000016857

In a Dutch patient of Chinese origin, Harteveld et al. (2001) identified a new hemoglobin variant, Hb 't Lange Land, caused by a GGT-to-CGT transversion at codon 136 in exon 3 of the HBB gene, predicted to result in a gly136-to-arg (G136R) substitution. The authors stated that 3 mutations inducing a single amino acid substitution at codon 136 were known: Hb Hope (gly136 to asp; 141900.0112), and 2 others based on personal communication from H. Wajcman, Hb Petit Bourg (gly136 to ala) and Hb Perpignan (gly136 to ser).


.0502   HEMOGLOBIN D (AGRI)

HBB, SER9TYR AND GLU121GLN
SNP: rs33918131, gnomAD: rs33918131, ClinVar: RCV000016317, RCV000016617, RCV000016758, RCV000016858, RCV000016886, RCV000029994, RCV000202465, RCV000723826, RCV000778329, RCV001175348, RCV002247348

In an asymptomatic Indian male belonging to the Agri caste group and originating from Mumbai in Maharashtra State, India, Colah et al. (2001) found a new hemoglobin variant, Hb D (Agri), with 2 amino acid substitutions in the same beta chain: glu121 to gln (141900.0065) and ser9 to tyr.


.0503   HEMOGLOBIN ANTALYA

HBB, 9-BP DEL/INS
SNP: rs2133589604, rs34058656, rs63750729, gnomAD: rs34058656, rs63750729, ClinVar: RCV001078387, RCV001789802

Keser et al. (2001) identified a 9-bp (TCTGACTCT) deletion/insertion at codons 3-5 of the HBB gene in a 26-year-old woman with beta-thalassemia trait. The change was found to be the result of a deletion of cytosine (-C) at codon 5 (1 of the nucleotides in the thirteenth or fourteenth position of exon 1), and an insertion of thymine (+T) in front of codon 3 at the tenth nucleotide in exon 1 of the HBB gene. As a result of these mutations, the amino acids at codons 3-5 were changed from leu-thr-pro to ser-asp-ser. This partial frameshift mutation led to a very unstable beta-globin chain.


.0504   HEMOGLOBIN LIMASSOL

HBB, LYS8ASN
SNP: rs35198910, gnomAD: rs35198910, ClinVar: RCV000016860

Kyrri et al. (2001) found a nonpathologic Hb variant in a Greek Cypriot male originating from Limassol, a town on the south coast of Cyprus. A G-to-C substitution in codon 8 (AAG to AAC) led to a lys8-to-asn (K8N) amino acid substitution. The 4 previously described amino acid substitutions at residue 8 of the beta-globin chain (lys8 to thr, 141900.0237; lys8 to gln, 141900.0135; lys8 to glu, 141900.0191; and lys8 to met, 141900.0460), and the 2 hemoglobin variants with amino acid substitutions at the equivalent residue of the alpha-globin chain (lys7 to asn, 141800.0187 and lys7 to glu, 141800.0192) are nonpathologic as well.


.0505   THALASSEMIA INTERMEDIA

HBB, DEL, SOMATIC
SNP: rs34533941, ClinVar: RCV000016861

Badens et al. (2002) described a 'new' mechanism leading to thalassemia intermedia (613985), a moderate form of thalassemia: a somatic deletion of the HBB gene in the hemopoietic lineage of a heterozygous beta-thalassemic patient. The deletion occurred on the chromosome 11 inherited from the mother, who had no abnormality of the HBB gene. The father had a beta-thalassemic trait due to the Mediterranean HBB nonsense mutation (141900.0312). The deletion gave rise to a mosaic of cells with either 1 or no functional beta-globin gene and it extended to a region of frequent loss of heterozygosity called LOH11A, which is located close to the HBB locus. Thus, loss of heterozygosity can be a cause of nonmalignant genetic disease.


.0506   HEMOGLOBIN CANTERBURY

HBB, CYS112PHE
SNP: rs33932908, ClinVar: RCV000016862

Brennan et al. (2002) found hemoglobin Canterbury by chance when a supposedly normal lysate was used as a control for an isopropanol stability test. The sample came from a 55-year-old man with Cowden disease (601728). The isopropanol stability test showed a precipitate, suggesting a slightly unstable hemoglobin.


.0507   HEMOGLOBIN O (TIBESTI)

HBB, GLU121LYS, VAL11ILE
SNP: rs33946267, rs33974228, gnomAD: rs33946267, rs33974228, ClinVar: RCV000016370, RCV000016524, RCV000016525, RCV000016577, RCV000016863, RCV000029993, RCV000202511, RCV000508438, RCV000587075, RCV000756241, RCV001104053, RCV001107684, RCV001107685, RCV001107686, RCV001778655, RCV002476974, RCV002482873

Prehu et al. (2002) described a heterozygous hemoglobin variant that combined the change of Hb O-Arab (141900.0202) and Hb Hamilton (141900.0099) on the same HBB allele. The other allele carried the Hb S mutation (141900.0243). The patient was a child of Chad-Sudanese descent, suffering from a sickle cell syndrome. Compared to the classic description of the Hb S/Hb O-Arab association, the additional Hb Hamilton mutation did not seem to modify the clinical presentation.


.0508   HEMOGLOBIN MOLFETTA

HBB, VAL126LEU
SNP: rs35658323, ClinVar: RCV000016864

Qualtieri et al. (2002) identified a new neutral hemoglobin variant in a pregnant Italian woman that resulted from a GTG-to-CTG replacement at codon 126 of the HBB gene, corresponding to a val-to-leu amino acid change. Thermal and isopropanol stability tests were normal and there were no abnormal clinical features.


.0509   BETA-THALASSEMIA, DOMINANT

HBB, 1-BP DEL
ClinVar: RCV001731306

Waye et al. (2002) described a case of dominant beta-thalassemia (613985) in a 38-year-old Canadian male of northern European extraction. He was anemic at birth and required periodic blood transfusions until about 2 years of age. Subsequently, he was under close medical supervision for his anemia and thrombocytosis, but did not require further transfusions. He had been asymptomatic throughout childhood. At age 20 years, he was found to have splenomegaly, and splenectomy was performed at age 23 because of mild symptoms and to prevent splenic rupture during karate competitions. After surgery he received Pneumovax, a prophylaxis against pneumococcal infections. He remained on folic acid supplementation, which had been started in childhood. The family history was negative for hematologic disorders. He was shown to have the normal complement of 4 alpha-globin genes. He was heterozygous for a single-nucleotide deletion in the HBB gene converting codon 113 from GTG to TG. This frameshift mutation was predicted to give rise to an extended beta chain of 156 amino acid residues. It was considered to be a de novo mutation. The mutation in this case most closely resembled that of Hb Geneva (141900.0335), an unstable beta-chain variant due to a complex rearrangement at codon 114. Both mutations give rise to extended beta chain variants of 156 amino acids differing only at residues 113 and 114 (cys-val for the codon 113 mutation and val-gly for the codon 114 mutation). In both instances, it was not possible to detect even a trace of the predicted Hb variant in carriers of the mutation.

Waye et al. (2002) stated that more than 30 dominant beta-thalassemia alleles had been reported.


.0510   HEMOGLOBIN KODAIRA II

HBB, HIS146GLN
SNP: rs33985739, ClinVar: RCV000016868

So et al. (2002) described a 35-year-old woman in whom a beta-chain variant was found on assay for Hb A(1c) performed because of impaired glucose tolerance during pregnancy. The raised hemoglobin level was suggestive of a hemoglobin variant with high oxygen affinity. The patient was heterozygous for a CAC-to-CAG transversion at codon 146, corresponding to a substitution of histidine by glutamine in the beta-globin chain. The same amino acid substitution at codon 146 occurs in the high oxygen affinity variant Hb Kodaira (141900.0409); however, Hb Kodaira resulted from a point mutation of CAC-to-CAA at codon 146. Not unexpectedly, the phenotypic manifestation of the 2 mutations was identical. This second form of his146 to gln (H146Q) was referred to as hemoglobin Kodaira II.

Ngiwsara et al. (2003) described a case of Hb Kodaira II in Thailand.


.0511   HEMOGLOBIN ILMENAU

HBB, PHE41CYS
SNP: rs33926796, ClinVar: RCV000016865

Prehu et al. (2002) described a novel unstable hemoglobin variant with low oxygen affinity and called it Hb Ilmenau for the city where the patient lived. The variant hemoglobin had a phe41-to-cys (F41C) substitution due to a TTC-to-TGC transversion in codon 41. The patient was a 29-year-old man who had suffered from anemia since childhood. When he was 4 years old, a nonspherocytic anemia was diagnosed with hepatosplenomegaly and cyanosis for which no cardiac origin could be found. He was splenectomized at the age of 8 years, without any significant clinical or biologic improvement.


.0512   HEMOGLOBIN AUBAGNE

HBB, GLY64ALA
SNP: rs33922018, ClinVar: RCV000016866, RCV001811166

In a 32-year-old woman from Provence, southeast France, Lacan et al. (2002) found a novel unstable beta-chain variant with a GGC-GCC transversion resulting in a gly64-to-ala (G64A) substitution. The presence of Heinz bodies and reduced percentage (23 to 35%) of the abnormal hemoglobin fraction suggested a moderate instability in the hemoglobin, which the authors designated Hb Aubagne.


.0513   HEMOGLOBIN COLIMA

HBB, SER49CYS
SNP: rs33960931, ClinVar: RCV000016869, RCV003476901

Cobian et al. (2002) found Hb Colima, a ser49-to-cys change (S49C) of the beta-globin chain, in a 52-year-old Mestizo female who was born in Colima, Mexico. This was the second mutation at beta-49, the first being Hb Las Palmas (ser49 to phe), a slightly unstable variant (141900.0155).


.0514   HEMOGLOBIN POCOS DE CALDAS

HBB, LYS61GLN
SNP: rs33995148, ClinVar: RCV000016870

During a screening for hemoglobinopathies in blood donors in Brazil, Kimura et al. (2002) identified a beta-globin variant in a 30-year-old Caucasian woman of mixed Native Indian and Italian origin. The base substitution in codon 61 of the HBB gene from AAG to CAG caused a lys-to-gln (K61Q) change. This was the fourth description of a missense mutation at lys61 of the HBB gene: see Hb N-Seattle (K61E; 141900.0190), found in a black American blood donor; Hb Hikari (K61N; 141900.0106), found in a Japanese family; and Hb Bologna (K61M; 141900.0024), found in a northern Italian family. The missense mutations found at this position (external contacts of the Hb molecule) did not cause clinical manifestations; all the carriers described had been asymptomatic.


.0515   HEMOGLOBIN TRENTO

HBB, 1-BP DEL, 144A
SNP: rs63751425, ClinVar: RCV000016871

In a 31-year-old woman from Trento in northeastern Italy, Ivaldi et al. (2003) found anomalous hemoglobin: an elongated C-terminal variant due to deletion of an A in codon 144. The deletion led to the replacement of lysine by serine at residue 144, the disappearance of the stop codon at position 147, and the presence of 12 additional residues, identical to those observed in hemoglobins Saverne (141900.0255), Tak (141900.0279), and Cranston (141900.0057), which result from a similar mechanism. Hb Trento, amounting to 29% of the total hemoglobin, was unstable and, like the other variants of this group, had an increased oxygen affinity. It led to a mild compensated hemolytic anemia with red cell inclusion bodies.


.0516   HEMOGLOBIN SANTANDER

HBB, VAL34ASP
SNP: rs1135101, ClinVar: RCV000016872

In a 22-year-old Spanish male presenting with jaundice and suffering from hemolytic crises during infections, Villegas et al. (2003) identified an unstable Hb variant in which the valine residue at position 34 of the beta-globin chain was replaced by aspartic acid (val34 to asp; V34D).


.0517   HEMOGLOBIN BUZEN

HBB, ALA138THR
SNP: rs33919821, ClinVar: RCV000016873

During glycohemoglobin determination by HPLC in a 76-year-old Japanese woman, Miyazaki et al. (2003) identified a homozygous change of codon 138 of the HBB gene from GCT (ala) to ACT (thr) (A138T). No information on the clinical state of the patient was provided. In Hb Brockton (141900.0032), ala138 is changed to pro. Heinz body hemolytic anemia has been observed with that mutation.


.0518   HEMOGLOBIN SANTA CLARA

HBB, HIS97ASN
SNP: rs33950993, ClinVar: RCV000016874

In a 6-month-old infant and in her mother of Mexican ancestry who lived in San Jose, California, Hoyer et al. (2003) identified a hemoglobin variant with abnormal oxygen affinity, designated Hb Santa Clara. A change of codon 97 of the HBB gene from CAC to AAC resulted in a his97-to-asn (H97N) change. Both the infant and her mother exhibited mild erythrocytosis.


.0519   HEMOGLOBIN SPARTA

HBB, PHE103VAL
SNP: rs33921589, ClinVar: RCV000016875

In a 29-year-old Caucasian woman who lived near Sparta, Michigan, Hoyer et al. (2003) identified a hemoglobin variant with high oxygen affinity, designated Hb Sparta. A smoker of 1 pack per day for 15 years, she was found to have mild erythrocytosis. A change of codon 103 of the HBB gene from TTC to GTC resulted in a phe103-to-val (F103V) change. Phe103 is replaced by leu in Hb Heathrow (141900.0102), and by ile in Hb Saint Nazaire (141900.0436); both variants are associated with erythrocytosis.


.0520   BETA-THALASSEMIA, DOMINANT INCLUSION BODY TYPE

HBB, INS/DEL, EX3
SNP: rs281864904, rs63750860, ClinVar: RCV001078374, RCV001789787

Weatherall et al. (1973) described an Irish family with an unusual form of beta-thalassemia (613985) that was characterized by anemia, splenomegaly, and gross abnormalities of the erythrocytes and their precursors; the disorder was transmitted through several generations in an autosomal dominant fashion. Initially the disorder was labeled dyserythropoietic anemia, congenital, Irish or Weatherall type (603902). Thein et al. (1990) restudied the Irish family and 3 similarly affected kindreds, all of Anglo-Saxon origin, and pointed to similar cases reported by others and to the fact that the designation inclusion body beta-thalassemia had been proposed (Stamatoyannopoulos et al., 1974). All affected members of the original Irish family had a moderate anemia with splenomegaly, increased levels of Hb A2 and Hb F, and increased alpha/beta chain synthesis ratios. Two family members had undergone splenectomy. By the time of the report of Thein et al. (1990), 1 family member had died, showing at autopsy extensive extramedullary hemopoiesis and iron overload in parenchymal tissues in a pattern typical of excessive iron absorption rather than transfusion. The family had a complex rearrangement in the third exon of the HBB gene that involved 2 deletions, 1 of 4 bp in codons 128 and 129 and the other of 11 bp in codons 132-135. The deletions were interrupted by an insertion of 5 bp, CCACA, followed by the normal sequence of 8 nucleotides. The modification resulted in a frameshift reading through to codon 153, predicting the synthesis of a variant beta-globin 7 residues longer than normal. Thein et al. (1990) suggested that the phenotypic difference between this condition and the more common recessive forms of beta-thalassemia lies mainly in the length and stability of the abnormal translation products that are synthesized and, in particular, whether they are capable of binding heme and producing aggregations that are relatively resistant to proteolytic degradation.


.0521   HEMOGLOBIN S (CAMEROON)

HBB, GLU6VAL AND GLU90LYS
SNP: rs334, rs33913712, gnomAD: rs334, ClinVar: RCV000016244, RCV000016286, RCV000016573, RCV000016574, RCV000016575, RCV000016576, RCV000016577, RCV000016579, RCV000016580, RCV000016877, RCV000016879, RCV000030905, RCV000224000, RCV000477892, RCV000576548, RCV000623118, RCV000723337, RCV000756232, RCV001192494, RCV001255121, RCV001535873, RCV001824571, RCV001835627, RCV002222351, RCV002251908, RCV002288496, RCV003150808, RCV003407340

Bundgaard et al. (2004) described a hemoglobin variant with 2 amino acid substitutions: Hb S, which is a glu6-to-val substitution (G6V; 141900.0243), and Hb Agenogi, which is a glu90-to-lys substitution (G90K; 141900.0003). As the patient originated from Cameroon, the variant was designated Hb S (Cameroon). The authors stated that 4 double mutations on the same allele with the Hb S variant had previously been described: Hb S (Antilles) (141900.0244), Hb S (Providence) (141900.0246), Hb S (Oman) (141900.0245), and Hb S (Travis) (141900.0247).


.0522   HEMOGLOBIN CARDARELLI

HBB, ALA86PRO
SNP: rs33952147, gnomAD: rs33952147, ClinVar: RCV000016553, RCV000016878

In several members of a family from Naples, Italy, Pagano et al. (2004) identified a change of codon 86 of the HBB gene from GCC (ala) to CCC (pro) (A86P). The variant, which is unstable and has high oxygen affinity, was designated Hb Cardarelli. The A86P mutation had previously been found in the doubly substituted, unstable, and hyperaffine variant Hb Poissy (141900.0223), in which it occurs in combination with gly56-to-arg of Hb Hamadan (G56R; 141900.0098).


.0523   HEMOGLOBIN JAMAICA PLAIN

HBB, GLU6VAL AND LEU68PHE
SNP: rs334, rs33961459, gnomAD: rs334, ClinVar: RCV000016286, RCV000016573, RCV000016574, RCV000016575, RCV000016576, RCV000016577, RCV000016579, RCV000016580, RCV000016877, RCV000016879, RCV000016880, RCV000030905, RCV000224000, RCV000477892, RCV000576548, RCV000623118, RCV000723337, RCV001192494, RCV001255121, RCV001535873, RCV001811167, RCV001824571, RCV002251908, RCV002288496, RCV002482878, RCV003150808, RCV003407340

Geva et al. (2004) described a girl of Puerto Rican descent who presented with symptomatic sickle cell disease exacerbated by mild hypoxemia, despite a newborn screening diagnosis of sickle cell trait. The child was found to be heterozygous for mutations in the HBB gene: the sickle cell mutation glu6 to val (G6V; 141900.0243), and a neutral leu68-to-phe (L68F; 141900.0524) mutation. Analysis of the patient's hemoglobin demonstrated that the doubly mutant protein, which the authors called hemoglobin Jamaica Plain (Hb JP) for Jamaica Plain, Massachusetts, had severely reduced oxygen affinity, especially in the presence of 2,3-diphosphoglycerate. Structural modeling suggested destabilization of the oxy conformation as a molecular mechanism for sickling in a heterozygote at an ambient partial pressure of oxygen. The patient's sickle cell disease was exacerbated by intercurrent respiratory infection, and she developed splenomegaly. The splenomegaly and anemia were recurrent. At the age of 19 months, during her first airplane trip, the child became acutely ill, with her spleen reaching the pelvic brim, as reported by a physician on board. After landing, she was hospitalized and found to have a hematocrit of 18%. Packed red cells were transfused; the hematocrit then rose to 28% with resolution of symptoms and a decrease in splenomegaly. Because of the apparent splenic sequestration crisis, a splenectomy was performed when she was 2 years old. Since that time, she had been asymptomatic and required no transfusions in the previous 24 months. In a commentary on the work of Geva et al. (2004), Benz (2004) noted that by itself, the L68F mutation is known as hemoglobin Rockford, a member of a class of 'low affinity hemoglobins' with reduced affinity for oxygen. These hemoglobins cause few symptoms, if any. When the L68F and G6V mutations coexist in the same beta-globin molecule, the L68F mutation causes Hb JP to desaturate easily and therefore to sickle more readily than ordinarily occurs with Hb S (G6V).


.0524   HEMOGLOBIN ROCKFORD

HBB, LEU68PHE
SNP: rs33961459, ClinVar: RCV000016879, RCV000016880, RCV001811167, RCV002482878

Perrault et al. (1997) described a low-affinity, stable hemoglobin variant that did not result in hemolysis, which they designated Hb Rockford; the variant is caused by a 335C-T transition in the HBB gene, resulting in a leu68-to-phe (L68F) substitution. Geva et al. (2004) described a hemoglobin variant with 2 amino acid substitutions, Hb Rockford and Hb S (G6V; 141900.0243), which they designated Hb Jamaica Plain (141900.0523).


.0525   HEMOGLOBIN TRIPOLI

HBB, GLU26ALA
SNP: rs33915112, ClinVar: RCV000016881

In a 5-year-old boy of Libyan origin living in Tripoli, Libya, Lacan et al. (2004) identified a change of codon 26 of the HBB gene from GAG (glu) to GCG (ala) (glu26 to ala). They designated this hemoglobin variant Hb Tripoli.


.0526   HEMOGLOBIN TIZI-OUZOU

HBB, GLY29SER
SNP: rs33974277, ClinVar: RCV000016882

In a 66-year-old man born in Tizi-Ouzou in northeastern Algeria, Lacan et al. (2004) described abnormal hemoglobin with change of codon 29 in the first exon of the HBB gene from GGC (gly) to AGC (ser) (gly29 to ser). The carrier showed hematologic abnormalities; the presence of microcytosis and hypochromia was explained by an additional homozygous 3.7 kb alpha(+)-thalassemic deletion.


.0527   BETA-PLUS-THALASSEMIA

HBB, 3-UNT, T-A, +3
SNP: rs33978907, gnomAD: rs33978907, ClinVar: RCV000016883

In a Tunisian patient with thalassemia intermedia (613985), Jacquette et al. (2004) identified compound heterozygosity for mutations in the HBB gene: a change from AATAAA to AAAAAA in the polyadenylation site of the gene and a 2-bp insertion (25insTA) in codon 9 (141900.0528), causing a frameshift with a premature termination at codon 19.


.0528   BETA-PLUS-THALASSEMIA

HBB, 2-BP INS, 25TA
SNP: rs1847587286, ClinVar: RCV001078420, RCV002280787

See 141900.0527 and Jacquette et al. (2004).


.0529   BETA-PLUS-THALASSEMIA

HBB, 1-BP DEL, C
SNP: rs281865475, ClinVar: RCV001001032, RCV002280785, RCV002282367, RCV002477786

In 4 members of a Mexican family with beta-plus-thalassemia (613985), Perea et al. (2004) identified heterozygosity for a 1-bp deletion (a cytosine) in the HBB gene, resulting in a frameshift. The 1-bp deletion was either in codon 77, changing CAC (his) to CA, or in codon 78, changing CTG (leu) to TG.


.0530   BETA-PLUS-THALASSEMIA

HBB, -101C-G, PROMOTER
SNP: rs63751208, gnomAD: rs63751208, ClinVar: RCV000016853

The expression 'silent beta-thalassemia' (613985) is used to indicate a group of thalassemia mutations that, in the heterozygous state, are characterized by normal hematologic indices, normal or borderline HbA2 (141850) and HbF levels, and a slight imbalance of beta-globin chain synthesis (Weatherall and Clegg, 2001). These mutations are usually identified by genetic and molecular analysis of families in which a proband is affected by thalassemia intermedia resulting from a compound heterozygous state for a typical beta-thalassemia and silent beta-thalassemia. One of the most common silent beta-thalassemia mutations, described in several Mediterranean populations, is the C-to-T substitution at position -101 in the distal CACCC box (141900.0370), which leads to a moderate reduction of the expression level of the beta-globin gene. In a silent beta-thalassemia carrier of Ashkenazi Jewish descent, Moi et al. (2004) identified a C-to-G transversion at the -101 position within the distal CACCC box of the HBB gene.


.0531   HEMOGLOBIN HOKUSETSU

HBB, ASP52GLY
SNP: rs33919924, ClinVar: RCV000016825

During the assay of Hb A(1c) in a diabetic patient, Nakanishi et al. (1998) identified a beta-chain variant: a change of codon 52 in exon 2 of the HBB gene from asp (GAT) to gly (GGT) (asp52 to gly). The patient was hematologically normal.


.0532   HEMOGLOBIN KOCHI

HBB, LEU141VAL, LYS144TER
SNP: rs33964352, rs33970699, ClinVar: RCV000016884, RCV003478200

In a 53-year-old Japanese woman who underwent routine Hb A(1c) assay, Miyazaki et al. (2005) identified 2 mutations in the same HBB gene: codon 141 was changed from CTG (leu) to GTG (val) (L141V), and codon 144 was changed from AAG (lys) to TAG (stop) (K144X), leading to deletion of the last 3 amino acids of the beta-globin chain, lys-tyr-his. The increased oxygen affinity of the hemoglobin was consistent with the presence of mild erythrocytosis.


.0533   HEMOGLOBIN ZOETERWOUDE

HBB, VAL23ALA
SNP: rs33945546, ClinVar: RCV000016885

In a 77-year-old Dutch woman with erythrocytosis, Harteveld et al. (2005) identified heterozygosity for a GTT-to-GCT transition at codon 23 of the HBB gene, causing a valine-to-alanine (V23A) amino acid change. This was the fourth single-nucleotide substitution at codon 23 of the HBB gene and the second that was associated with erythrocytosis.


.0534   HEMOGLOBIN BREM-SUR-MER

HBB, SER9TYR
SNP: rs33918131, gnomAD: rs33918131, ClinVar: RCV000016858, RCV000016886

In a 69-year-old man, Lacan et al. (2005) identified a TCT-to-TAT transversion in codon 9 of the HBB gene, resulting in a ser9-to-tyr (S9Y) amino acid change. No hematologic abnormalities were found. The patient lived in the town of Brem-sur-Mer on the Atlantic coast of France.


.0535   HEMOGLOBIN GELDROP ST. ANNA

HBB, ASP94TYR
SNP: rs33959340, ClinVar: RCV000016887

Harteveld et al. (2005) observed an abnormal hemoglobin fraction during an HPLC assay for Hb A(1c) control for diabetes mellitus in a 56-year-old northern European woman. This same abnormal fraction was found in 3 of her 5 sibs and in her son. There was no history of anemia, hemolytic, or circulatory episodes. Direct sequencing of the HBB gene revealed a GAC-to-TAC transversion in heterozygous form at codon 94. They concluded that the variant is a stable hemoglobin associated with a slightly elevated oxygen affinity. Harteveld et al. (2005) noted that this was the fourth mutation known to involve the asp94 residue of the HBB gene; see 141900.0016, 141900.0035, and 141900.0045. A frameshift mutation has also been reported at this position (141900.0338).


.0536   HEMOGLOBIN MARINEO

HBB, ALA70VAL
SNP: rs33946401, ClinVar: RCV000016888

In a 3-generation family from western Sicily, Giambona et al. (2006) identified heterozygosity for a GCC-GTC transition in the HBB gene, resulting in an ala70-to-val (A70V) substitution. Three mutations at codon 70 of the HBB gene had been previously described, all presenting with hemolytic anemia. In the new case, no anemia or other alteration of hematologic indices was found. The family lived in the town of Marineo near Palermo, Sicily.


.0537   HEMOGLOBIN LA CORUNA

HBB, THR38ILE
SNP: rs34703513, ClinVar: RCV000016889

Ropero et al. (2006) described Hb La Coruna, a novel hemoglobin variant with increased oxygen affinity, leading to erythrocytosis. It is an electrophoretically silent variant that can be detected by reversed-phase high performance liquid chromatography (HPLC) and characterized by DNA sequencing. The patient was a 22-year-old Spanish male whose family lived in La Coruna in the northwest of Spain. The mother was also a carrier.


.0538   HEREDITARY PERSISTENCE OF FETAL HEMOGLOBIN

DELTA/BETA THALASSEMIA, INCLUDED
HBB, 106-KB DEL
ClinVar: RCV000169772, RCV001814971

Kan et al. (1975) analyzed the DNA from a black patient with hereditary persistence of fetal hemoglobin (141749) and found evidence for a deletion of the beta-globin gene. Gallienne et al. (2009) cited several reports in which patients with delta/beta thalassemia (see 141749) or hereditary persistence of fetal hemoglobin had a 106-kb deletion of the beta globin gene cluster. This mutation has been designated HPFH1.


.0539   HEMOGLOBIN HANA

HBB, HIS63ASN
ClinVar: RCV000855777

In a Czech proband and her sister with Heinz body hemolytic anemia (140700) and elevated levels of methemoglobin, Mojzikova et al. (2010) identified a his63-to-asn (H63N) mutation in the HBB gene. Their mother carried the same mutation but had no anemia or evidence of hemolysis. Biochemical measurements of several erythrocyte antioxidant parameters revealed decreased glutathione reductase (GSR; 138300) activity in both affected sisters but not in their asymptomatic mother. Treatment of the patients with riboflavin increased GSR activity and ameliorated clinical manifestation of Heinz body hemolytic anemia due to unstable hemoglobinopathy.


.0540   BETA-THALASSEMIA, DOMINANT INCLUSION BODY TYPE

HBB, 11-BP DEL
ClinVar: RCV001549283

In a 51-year-old Spanish man with inclusion body beta-thalassemia (603902), Ropero et al. (2005) identified a heterozygous 11-basepair deletion in exon 3 of the HBB gene by direct sequencing. The deletion from codon 131 to codon 134 (-CAGAAAGTGGT) was predicted to produce a frameshift and synthesis of an abnormal and likely unstable beta-chain variant of 134 amino acids instead of the normal 146 amino acids. Inheritance could not be determined because the parents were deceased. The patient was diagnosed with beta-thalassemia in adulthood with marked siderosis, slight microcytic anemia that never needed transfusion, moderate hemolysis, subclinical jaundice, painful splenomegaly, and hepatomegaly. The patient was also homozygous for the H63D substitution in the HFE gene (613609.0002); the authors noted that the HFE variant increases the probability of developing iron overload when it is associated with beta-thalassemia, and suggested that it could contribute to siderosis.


.9999   HEMOGLOBIN BETA VARIANTS, MOLECULAR DEFECT UNKNOWN

HEMOGLOBIN CASERTA. Beta chain anomaly. See Ventruto et al. (1965) and Quattrin et al. (1970).

HEMOGLOBIN D (FRANKFURT). Beta chain anomaly. See Martin et al. (1960) and Gammack et al. (1961).

HEMOGLOBIN DURHAM-I (HEMOGLOBIN R). Beta chain anomaly. See Chernoff and Weichselbaum (1958) and Chernoff and Pettit (1964).

HEMOGLOBIN J (JAMAICA). Beta chain anomaly. See Gammack et al. (1961).

HEMOGLOBIN K. Beta chain anomaly. See O'Gorman et al. (1963).

HEMOGLOBIN KINGS COUNTY. Probably beta chain defect. Observed in an American black family. Affected persons had nonspherocytic hemolytic Heinz body anemia. See Sathiapalan and Robinson (1968).

HEMOGLOBIN L. Beta chain anomaly. See Ager and Lehmann (1957) and Gammack et al. (1961).


See Also:

Antonarakis et al. (1984); Antonarakis et al. (1982); Arous et al. (1982); Bank et al. (1980); Barwick et al. (1985); Bernards et al. (1979); Blackwell et al. (1971); Blackwell et al. (1972); Blackwell et al. (1970); Blackwell et al. (1972); Blackwell et al. (1970); Blackwell et al. (1969); Blackwell et al. (1969); Blackwell et al. (1969); Blouquit et al. (1984); Boyer et al. (1963); Brennan et al. (1977); Cai et al. (1989); Cai Yin Lin et al. (1982); Camaschella et al. (1987); Cao et al. (1981); Chang et al. (1983); Chang and Kan (1982); Charache et al. (1977); Chen et al. (1985); Chifu et al. (1992); Cole-Strauss et al. (1996); Collins et al. (1987); Ding et al. (2004); Driscoll et al. (1981); Efstratiadis et al. (1980); Enver et al. (1990); Forget (1979); Fritsch et al. (1980); Gacon et al. (1977); Garel et al. (1976); Gilbert et al. (2000); Gonzalez-Redondo et al. (1989); Gusella et al. (1979); Harano et al. (1985); Harano et al. (1990); Harano et al. (1991); Harano et al. (1990); Harano et al. (1990); Harano et al. (1983); Harano et al. (1981); Hebbel et al. (1977); Heller et al. (1966); Honig et al. (1990); Horst et al. (1983); Housman (1979); Idelson et al. (1974); Jeffreys and Flavell (1977); Johnson et al. (1980); Jones et al. (1967); Kan et al. (1977); Kan et al. (1975); Kan et al. (1980); Kaufman et al. (1980); Kohen et al. (1982); Lacombe et al. (1987); Lawn et al. (1980); Lebo et al. (1979); Li et al. (1990); Makhoul et al. (2005); Maniatis et al. (1980); Miyaji et al. (1968); Moo-Penn et al. (1977); Moo-Penn et al. (1976); Moo-Penn et al. (1977); Moo-Penn et al. (1980); Moo-Penn et al. (1978); Nakatsuji et al. (1981); Necheles et al. (1969); Novy et al. (1967); Ohba et al. (1983); Ohba et al. (1989); Ohba et al. (1985); Ohba et al. (1975); Ohta et al. (1971); Old et al. (1982); Orkin et al. (1978); Orkin et al. (1982); Orkin et al. (1980); Orkin et al. (1982); Orkin et al. (1983); Ottolenghi et al. (1976); Ottolenghi and Giglioni (1982); Ottolenghi et al. (1974); Pirastu et al. (1984); Plaseska et al. (1991); Plaseska et al. (1991); Plaseska et al. (1990); Prehu et al. (2002); Premawardhena et al. (2005); Proudfoot et al. (1980); Rahbar et al. (1981); Ricco et al. (1974); Rochette et al. (1984); Sanders-Haigh et al. (1980); Schiliro et al. (1981); Schneider et al. (1969); Scott et al. (1979); Shibata et al. (1961); Shibata et al. (1961); Smith and Conley (1959); Spritz (1981); Studencki et al. (1985); Tamagnini et al. (1983); Taylor et al. (1974); Tilghman et al. (1978); Tuan et al. (1985); Vella et al. (1967); Verma and Edwards (1978); Villegas et al. (1989); Weatherall and Clegg (1981); Williamson et al. (1983); Williamson et al. (1981); Yoon et al. (1996); Zeng and Huang (1982); Zhao et al. (1990); Zinkham et al. (1979)

REFERENCES

  1. Abourzik, N. N., Conlon, M., Zordon, G., Hine, T. K., Johnson, M. H., Jue, D. L., Moo-Penn, W. F. Hb St. Francis [beta-121(GH4)glu-to-gly]: a new mutation at the same site as Hb D-Los Angeles. Hemoglobin 15: 115-117, 1991. [PubMed: 1917532] [Full Text: https://doi.org/10.3109/03630269109072491]

  2. Adachi, K., Surrey, S., Tamary, H., Kim, J., Eck, H. S., Rappaport, E., Ohene-Frempong, K. Hb Shelby [beta-131(H9)gln-to-lys] in association with Hb S [beta-6(A3)glu-to-val]: characterization, stability, and effects on Hb S polymerization. Hemoglobin 17: 329-343, 1993. [PubMed: 8226094] [Full Text: https://doi.org/10.3109/03630269308997486]

  3. Adams, J. G., Boxer, L. A., Baehner, R. L., Forget, B. G., Tsistrokis, G. A., Steinberg, M. H. Hemoglobin Indianapolis: post-translational degradation of an unstable beta-chain variant producing a phenotype of severe heterozygous beta-thalassemia. (Abstract) Clin. Res. 26: 501A, 1978.

  4. Adams, J. G., Heller, P. Hemoglobin Arlington Park: a new hemoglobin variant with two amino acid substitutions in the beta chain. Hemoglobin 1: 419-426, 1977. [PubMed: 893139] [Full Text: https://doi.org/10.3109/03630267709027860]

  5. Adams, J. G., III, Morrison, W. T., Pullen, D. J., Abney, R. L., III, Steinberg, M. H. Hemoglobin Mississippi (MS): a new hemoglobin variant with three distinct electrophoretic mobilities. (Abstract) Clin. Res. 33: 603A, 1985.

  6. Adams, J. G., III, Przywara, K. P., Heller, P., Shamsuddin, M. Hemoglobin J Altgeld Gardens, a hemoglobin variant with a substitution of the proximal histidine of the beta-chain. Hemoglobin 2: 403-415, 1978. [PubMed: 721609] [Full Text: https://doi.org/10.3109/03630267809007075]

  7. Adams, J. G., III, Przywara, K. P., Shamsuddin, M., Heller, P. Hemoglobin J Altgeld Gardens (beta 92 (F8) his-to-asp): a new hemoglobin variant involving a substitution of the proximal histidine. (Abstract) Blood 46: 1029, 1975.

  8. Adams, J. G., III, Steinberg, M. H., Kazazian, H. H., Jr. Isolation and characterization of the translation product of a beta-globin gene nonsense mutation (beta121 GAA-to-TAA). Brit. J. Haemat. 75: 561-567, 1990. [PubMed: 2207008] [Full Text: https://doi.org/10.1111/j.1365-2141.1990.tb07799.x]

  9. Adams, J. G., III, Steinberg, M. H., Newman, M. V., Morrison, W. T., Benz, E. J., Jr., Iyer, R. Beta-thalassemia present in cis to a new beta-chain structural variant, Hb Vicksburg (beta-75(E19)leu-to-0). Proc. Nat. Acad. Sci. 78: 469-473, 1981. [PubMed: 6165992] [Full Text: https://doi.org/10.1073/pnas.78.1.469]

  10. Adams, J. G., III, Winter, W. P., Tausk, K., Heller, P. Hemoglobin Rush (beta 101 (G-3) glu-to-gln): a new unstable hemoglobin causing mild hemolytic anemia. Blood 43: 261-269, 1974. [PubMed: 4129558]

  11. Adams, J. G., Smith, C. M., Hedlund, B., Olson, M., Cich, J. A., Tukey, D. P., Steinberg, M. H. Hb North Shore: a hemoglobin variant which produces the phenotype of beta(+)-thalassemia. (Abstract) Clin. Res. 30: 499A, 1982.

  12. Adams, J. G., Steinberg, M. H., Boxer, L. A., Baehner, R. L., Forget, B. G., Tsistrakis, G. A. The structure of hemoglobin Indianapolis (beta112(G14) arginine): an unstable variant detectable only by isotopic labeling. J. Biol. Chem. 254: 3479-3482, 1979. [PubMed: 429365]

  13. Adamson, J. W., Hayashi, A., Stamatoyannopoulos, G., Burger, W. F. Erythrocyte function and marrow regulation in hemoglobin Bethesda (beta 145 histidine). J. Clin. Invest. 51: 2883-2888, 1972. [PubMed: 5080413] [Full Text: https://doi.org/10.1172/JCI107111]

  14. Adamson, J. W., Parer, J. T., Stamatoyannopoulos, G. Erythrocytosis associated with hemoglobin Rainier: oxygen equilibria and marrow regulation. J. Clin. Invest. 48: 1376-1386, 1969. [PubMed: 5796352] [Full Text: https://doi.org/10.1172/JCI106103]

  15. Agarwal, A., Guindo, A., Cissoko, Y., Taylor, J. G., Coulibaly, D., Kone, A., Kayentao, K., Djimde, A., Plowe, C. V., Doumbo, O., Wellems, T. E., Diallo, D. Hemoglobin C associated with protection from severe malaria in the Dogon of Mali, a West African population with a low prevalence of hemoglobin S. Blood 96: 2358-2363, 2000. [PubMed: 11001883]

  16. Agarwal, S., Hattori, Y., Gupta, U. R., Agarwal, S. S. A novel Indian beta-thalassemia mutation: Hb Lucknow (beta-8(A5)lys-to-arg). Hemoglobin 23: 263-265, 1999. [PubMed: 10490139] [Full Text: https://doi.org/10.3109/03630269909005707]

  17. Ager, J. A. M., Lehmann, H. Haemoglobin L: a new haemoglobin found in a Punjabi Hindu. Brit. Med. J. 2: 142-143, 1957. [PubMed: 13436881] [Full Text: https://doi.org/10.1136/bmj.2.5037.142]

  18. Ager, J. A. M., Lehmann, H. Observations on some 'fast' haemoglobins: K, J, N and 'Bart's'. Brit. Med. J. 1: 929-931, 1958. [PubMed: 13523233] [Full Text: https://doi.org/10.1136/bmj.1.5076.929]

  19. Aguinaga, M. P., Wright, C. J., Roa, P. D., Terrell, F., Turner, E. A., Houston, M. Molecular diagnosis and characterization of Hb Zurich [beta-63(E7)his to arg] carriers in a Kentucky family. Hemoglobin 22: 509-515, 1998. [PubMed: 9859934] [Full Text: https://doi.org/10.3109/03630269809071548]

  20. Ahern, E., Ahern, V., Hilton, T., Serjeant, G. R., Serjeant, B. E., Seakins, M., Lang, A., Middleton, A., Lehmann, H. Haemoglobin Caribbean beta 91(F7) leu-to-arg: a mildly unstable haemoglobin with a low oxygen affinity. FEBS Lett. 69: 99-102, 1976. [PubMed: 992050] [Full Text: https://doi.org/10.1016/0014-5793(76)80662-x]

  21. Akar, E., Ozdemir, S., Timur, I. H., Akar, N. First observation of homozygous hemoglobin Hamadan (B 56 (D7) gly-arg) and beta thalassemia (-29 G-A)-hemoglobin Hamadan combination in a Turkish family. Am. J. Hemat. 74: 280-282, 2003. [PubMed: 14635211] [Full Text: https://doi.org/10.1002/ajh.10404]

  22. Akar, N., Ozden, A., Akar, E., Cin, S., Arcasoy, A. Discrimination of Hb D Los Angeles (B121 glu-to-gln) and Hb Beograd (B121 glu-to-val) by dual restriction enzyme analysis. Am. J. Hemat. 48: 280-281, 1995. [PubMed: 7717379] [Full Text: https://doi.org/10.1002/ajh.2830480415]

  23. Aksoy, M., Erdem, S., Efremov, G. D., Wilson, J. B., Huisman, T. H. J., Schroeder, W. A., Shelton, J. R., Shelton, J. B., Ulitin, O. N., Muftuoglu, A. Hemoglobin Istanbul: substitution of glutamine for histidine in a proximal histidine (F8(92)beta). J. Clin. Invest. 51: 2380-2387, 1972. [PubMed: 4639022] [Full Text: https://doi.org/10.1172/JCI107050]

  24. Aksoy, M., Erdem, S. Differences between individuals with hemoglobins Istanbul and Saint-Etienne (beta 92 his-to-gln). Acta Haemat. 61: 295-297, 1979. [PubMed: 111458] [Full Text: https://doi.org/10.1159/000207675]

  25. Alami, R., Greally, J. M., Tanimoto, K., Hwang, S., Feng, Y.-Q., Engel, J. D., Fiering, S., Bouhassira, E. E. Beta-globin YAC transgenes exhibit uniform expression levels but position effect variegation in mice. Hum. Molec. Genet. 9: 631-636, 2000. [PubMed: 10699186] [Full Text: https://doi.org/10.1093/hmg/9.4.631]

  26. Ali, M. A. M., Pinkerton, P., Chow, S. W. S., Zaetz, S. D., Wilson, J. B., Webber, B. B., Hu, H., Kutlar, A., Kutlar, F., Huisman, T. H. J. Some rare hemoglobin variants with altered oxygen affinities: Hb Linkoping (beta36(C2)pro-to-thr), Hb Caribbean (beta91(F7)leu-to-arg), and Hb Sunnybrook (beta36(C2)pro-to-arg). Hemoglobin 12: 137-148, 1988. [PubMed: 3384706] [Full Text: https://doi.org/10.3109/03630268808998020]

  27. Allan, N., Beale, D., Irvine, D., Lehmann, H. Three haemoglobins K: Woolwich, an abnormal, Cameroon and Ibadan, two unusual variants of human haemoglobin A. Nature 208: 658-661, 1965.

  28. Allison, A. C. Protection afforded by sickle-cell trait against subtertian malarial infection. Brit. Med. J. 1: 290-294, 1954. [PubMed: 13115700] [Full Text: https://doi.org/10.1136/bmj.1.4857.290]

  29. Altay, C., Altinoz, N., Wilson, J. B., Bolch, K. C., Huisman, T. H. J. Hemoglobin Hacettepe or alpha-2-beta-2 127(H5) gln-to-glu. Biochim. Biophys. Acta 434: 1-3, 1976. [PubMed: 938658] [Full Text: https://doi.org/10.1016/0005-2795(76)90029-5]

  30. Amselem, S., Nunes, V., Vidaud, M., Estivill, X., Wong, C., d'Auriol, L., Vidaud, D., Galibert, F., Baiget, M., Goossens, M. Determination of the spectrum of beta-thalassemia genes in Spain by use of dot-blot analysis of amplified beta-globin DNA. Am. J. Hum. Genet. 43: 95-100, 1988. [PubMed: 2897787]

  31. Andersen, C. B. F., Torvund-Jensen, M., Nielsen, M. J., de Oliveira, C. L. P., Hersleth, H.-P., Andersen, N. H., Pedersen, J. S., Andersen, G. R., Moestrup, S. K. Structure of the haptoglobin-haemoglobin complex. Nature 489: 456-459, 2012. [PubMed: 22922649] [Full Text: https://doi.org/10.1038/nature11369]

  32. Anderson Fernandes, B. L. Hb N-Baltimore or beta95 (FG2) lys-to-glu in Portugal. Hemoglobin 13: 83-87, 1989. [PubMed: 2703368] [Full Text: https://doi.org/10.3109/03630268908998056]

  33. Anderson, N. L. Hemoglobin San Diego (beta 109 (G11) val-to-met). Crystal structure of the deoxy form. J. Clin. Invest. 53: 329-333, 1974. [PubMed: 4808645] [Full Text: https://doi.org/10.1172/JCI107554]

  34. Anderson, N. L. Hemoglobin St. Louis (beta 28 (B10) leu-to-gln): crystal structure of the fully reduced (deoxy) form. J. Clin. Invest. 58: 1107-1109, 1976. [PubMed: 993333] [Full Text: https://doi.org/10.1172/JCI108562]

  35. Antonarakis, S. E., Boehm, C. D., Giardina, P. J. V., Kazazian, H. H., Jr. Non-random association of the polymorphic restriction sites in the beta-globin gene cluster. Proc. Nat. Acad. Sci. 79: 137-141, 1982. [PubMed: 6275383] [Full Text: https://doi.org/10.1073/pnas.79.1.137]

  36. Antonarakis, S. E., Boehm, C. D., Serjeant, G. R., Theisen, C. E., Dover, G. J., Kazazian, H. H., Jr. Origin of the beta-S-globin gene in blacks: the contribution of recurrent mutation or gene conversion or both. Proc. Nat. Acad. Sci. 81: 853-856, 1984. [PubMed: 6583683] [Full Text: https://doi.org/10.1073/pnas.81.3.853]

  37. Antonarakis, S. E., Orkin, S. H., Cheng, T.-C., Scott, A. F., Sexton, J. P., Trusko, S., Charache, S., Kazazian, H. H., Jr. Beta-thalassemia in American blacks: novel mutations in the TATA box and an acceptor splice site. Proc. Nat. Acad. Sci. 81: 1154-1158, 1984. [PubMed: 6583702] [Full Text: https://doi.org/10.1073/pnas.81.4.1154]

  38. Antonarakis, S. E., Orkin, S. H., Kazazian, H. H., Jr., Goff, S. C., Boehm, C. D., Waber, P. G., Sexton, J. P., Ostrer, H., Fairbanks, V. F., Chakravarti, A. Evidence for multiple origins of the beta-E-globin gene in Southeast Asia. Proc. Nat. Acad. Sci. 79: 6608-6611, 1982. [PubMed: 6292908] [Full Text: https://doi.org/10.1073/pnas.79.21.6608]

  39. Arcasoy, A., Casey, R., Lehmann, H., Cavdar, A. O., Berki, A. A new hemoglobin J from Turkey--Hb Ankara (beta 10 ala-to-asp). FEBS Lett. 42: 121-123, 1974. [PubMed: 4850241] [Full Text: https://doi.org/10.1016/0014-5793(74)80766-0]

  40. Arends, T., Castillo, O., Garlin, G., Maleh, Y., Anchustegui, M., Salazar, R. Hemoglobin Alamo (beta 19 (B1) asn-to-asp) in a Venezuelan family. Hemoglobin 11: 135-138, 1987. [PubMed: 3623973] [Full Text: https://doi.org/10.3109/03630268709005787]

  41. Arends, T., Garlin, G., Guevara, J. M., Amesty, C., Perez-Bandez, O., Lorkin, P. A., Lehmann, H., Castillo, O. Hemoglobin Hofu associated with beta-zero-thalassemia. Acta Haemat. 73: 51-54, 1985. [PubMed: 3923770] [Full Text: https://doi.org/10.1159/000206274]

  42. Arends, T., Lehmann, H., Plowman, D., Stathopoulou, R. Haemoglobin North Shore--Caracas (beta 134 (H12) valine-to-glutamic acid). FEBS Lett. 80: 261-265, 1977. [PubMed: 891976] [Full Text: https://doi.org/10.1016/0014-5793(77)80453-5]

  43. Arous, N., Braconnier, F., Thillet, J., Blouquit, Y., Galacteros, F., Chevrier, M., Bordahandy, C., Rosa, J. Hemoglobin Saint Mande beta102 (G4) asn-to-tyr: a new low oxygen affinity variant. FEBS Lett. 126: 114-116, 1981. [PubMed: 7238856] [Full Text: https://doi.org/10.1016/0014-5793(81)81046-0]

  44. Arous, N., Galacteros, F., Fessas, P., Loukopoulos, D., Blouquit, Y., Komis, G., Sellaye, M., Boussiou, M., Rosa, J. Hemoglobin Knossos, beta27 ala-to-ser (B9): a new hemoglobinopathy presenting as a silent beta-thalassemia. (Abstract) Blood 60: 51A, 1982.

  45. Arous, N., Galacteros, F., Fessas, P., Loukopoulos, D., Blouquit, Y., Komis, G., Sellaye, M., Boussiou, M., Rosa, J. Structural study of hemoglobin Knossos, beta27(B9) ala-to-ser: a new abnormal hemoglobin present as a silent beta-thalassemia. FEBS Lett. 147: 247-250, 1982. [PubMed: 7173395] [Full Text: https://doi.org/10.1016/0014-5793(82)81052-1]

  46. Arrizabalaga, B., Erkiaga, A., Villegas, A., Carreno, D. L. A case of Hb J-Chicago [beta-76(E20)ala-to-asp] in a Spanish family. Hemoglobin 22: 75-78, 1998. [PubMed: 9494051] [Full Text: https://doi.org/10.3109/03630269809071520]

  47. Asakura, T., Adachi, K., Schwartz, E., Wiley, J. Molecular stability of Hb Philly (beta 35 (C1) tyr-to-phe): the relationship of hemoglobin stability to ligand state as defined by heat and mechanical shaking tests. Hemoglobin 5: 177-190, 1981. [PubMed: 7216817] [Full Text: https://doi.org/10.3109/03630268108996923]

  48. Atweh, G. F., Anagnou, N. P., Forget, B. G., Kaufman, R. E. Beta-thalassemia resulting from a single nucleotide substitution in an acceptor splice site. Nucleic Acids Res. 13: 777-790, 1985. [PubMed: 2987809] [Full Text: https://doi.org/10.1093/nar/13.3.777]

  49. Atweh, G. F., Brickner, H. E., Zhu, X.-X., Kazazian, H. H., Jr., Forget, B. G. New amber mutation in a beta-thalassemic gene with nonmeasurable levels of mutant messenger RNA in vivo. J. Clin. Invest. 82: 557-561, 1988. [PubMed: 3403716] [Full Text: https://doi.org/10.1172/JCI113632]

  50. Atweh, G. F., Wong, C., Reed, R., Antonarakis, S. E., Zhu, D., Ghosh, P. K., Maniatis, T., Forget, B. G., Kazazian, H. H., Jr. A new mutation in IVS-1 of the human beta-globin gene causing beta-thalassemia due to abnormal splicing. Blood 70: 147-151, 1987. [PubMed: 2439149]

  51. Aulehla-Scholz, C., Spiegelberg, R., Horst, J. A beta-thalassemia mutant caused by a 300-bp deletion in the human beta-globin gene. Hum. Genet. 81: 298-299, 1989. [PubMed: 2921044] [Full Text: https://doi.org/10.1007/BF00279010]

  52. Badens, C., Mattei, M. G., Imbert, A. M., Lapoumeroulie, C., Martini, N., Michel, G., Lena-Russo, D. A novel mechanism for thalassaemia intermedia. Lancet 359: 132-133, 2002. [PubMed: 11809258] [Full Text: https://doi.org/10.1016/s0140-6736(02)07338-5]

  53. Badr, F. M., Lorkin, P. A., Lehmann, H. Haemoglobin P-Nilotic, containing a beta-delta chain. Nature N.B. 242: 107-110, 1973. [PubMed: 4513408] [Full Text: https://doi.org/10.1038/newbio242107a0]

  54. Baglioni, C., Ingram, V. M. Four adult haemoglobin types in one person. Nature 189: 465-467, 1961. [PubMed: 13685866] [Full Text: https://doi.org/10.1038/189465a0]

  55. Baiget, M., Gomez Pereira, C., Jue, D. L., Johnson, M. H., McGuffey, J. E., Moo-Penn, W. F. A case of hemoglobin Indianapolis (beta112(G14) cys-to-arg) in an individual from Cordoba, Spain. Hemoglobin 10: 483-494, 1986. [PubMed: 3781865] [Full Text: https://doi.org/10.3109/03630268609014133]

  56. Baine, R. M., Wright, J. M., Johnson, M. H., Cadena, C. L. Biosynthetic evidence for instability of Hb M Saskatoon. Hemoglobin 4: 201-207, 1980. [PubMed: 6248489] [Full Text: https://doi.org/10.3109/03630268009042387]

  57. Baird, M., Driscoll, C., Schreiner, H., Sciarratta, G. V., Sansone, G., Niazi, G., Ramirez, F., Bank, A. A nucleotide change at a splice junction in the human beta-globin gene is associated with beta-zero-thalassemia. Proc. Nat. Acad. Sci. 78: 4218-4221, 1981. [PubMed: 6270663] [Full Text: https://doi.org/10.1073/pnas.78.7.4218]

  58. Baklouti, F., Giraud, Y., Francina, A., Richard, G., Favre-Gilly, J., Delaunay, J. Hemoglobin Pierre-Benite (beta90 (F6) glu-to-asp), a new high affinity variant found in a French family. Hemoglobin 12: 171-177, 1988. [PubMed: 3384709] [Full Text: https://doi.org/10.3109/03630268808998023]

  59. Baklouti, F., Giraud, Y., Francina, A., Richard, G., Perier, C., Geyssant, A., Jaubert, J., Brizard, C., Delaunay, J. Hemoglobin Grange-Blanche (beta27 (B9) ala-to-val), a new variant with normal expression and increased affinity for oxygen. FEBS Lett. 223: 59-62, 1987. [PubMed: 3666141] [Full Text: https://doi.org/10.1016/0014-5793(87)80509-4]

  60. Ballas, S. K., Lewis, C. N., Noone, A. M., Krasnow, S. H., Kamarulzaman, E., Burka, E. R. Clinical, hematological, and biochemical features of Hb SC disease. Am. J. Hemat. 13: 37-51, 1982. [PubMed: 7137165] [Full Text: https://doi.org/10.1002/ajh.2830130106]

  61. Ballas, S. K., Park, D. K. Biosynthetic evidence for stability of Hb N-Baltimore. Hemoglobin 9: 489-494, 1985. [PubMed: 4086303] [Full Text: https://doi.org/10.3109/03630268508997026]

  62. Baltzan, D. M., Sugarman, H. Hereditary cyanosis. Canad. Med. Assoc. J. 62: 348-350, 1950. [PubMed: 20324533]

  63. Bank, A., Mears, J. G., Ramirez, F., Burns, A. L., Spence, S., Feldenzer, J., Baird, M. The organization of the gamma-delta-beta gene complex in normal and thalassemia cells. Hemoglobin 4: 497-507, 1980. [PubMed: 6252123] [Full Text: https://doi.org/10.3109/03630268008996230]

  64. Barany, F. Genetic disease detection and DNA amplification using cloned thermostable ligase. Proc. Nat. Acad. Sci. 88: 189-193, 1991. [PubMed: 1986365] [Full Text: https://doi.org/10.1073/pnas.88.1.189]

  65. Barbosa, C. A. A., Koury, W. H., Krieger, H. Linkage data on MN and the Hb beta locus. Am. J. Hum. Genet. 27: 797-801, 1975. [PubMed: 1200031]

  66. Bardakdjian, J., Arous, N., Kister, J., Blouquit, Y., Giacomini, T., Lacombe, C., Riou, J., Hafsia, R., Rosa, J., Galacteros, F. Further characterization of Hb Henri Mondor or beta26(B8)glu-to-val. Hemoglobin 11: 1-11, 1987. [PubMed: 3583762] [Full Text: https://doi.org/10.3109/03630268709036574]

  67. Bardakdjian, J., Kister, J., Rhoda, M. D., Marden, M., Arous, N., De Leon, J., North, M. L., Lacombe, C., Blouquit, Y., Castracane, C., Riou, J., Rosa, J., Galacteros, F. Hb J-Cordoba (beta95(FG2)lys-to-met): a new Hb variant found in Argentina. Hemoglobin 12: 1-11, 1988. [PubMed: 3384693] [Full Text: https://doi.org/10.3109/03630268808996877]

  68. Bardakdjian, J., Leclerc, L., Blouquit, Y., Oules, O., Rafaillat, D., Arous, N., Bohn, B., Poyart, C., Rosa, J., Galacteros, F. A new case of hemoglobin Providence (beta82 (EF6) lys-to-asn or asp) discovered in a French Caucasian family: structural and functional studies. Hemoglobin 9: 333-348, 1985. [PubMed: 3935609] [Full Text: https://doi.org/10.3109/03630268508997009]

  69. Bardakdjian-Michau, J., Fucharoen, S., Delanoe-Garin, J., Kister, J., Lacombe, C., Winichagoon, P., Blouquit, Y., Riou, J., Wasi, P., Galacteros, F. Hemoglobin Dhonburi beta126 (H4) val-to-gly: a new unstable beta variant producing a beta-thalassemia intermedia phenotype in association with beta-zero-thalassemia. Am. J. Hemat. 35: 96-99, 1990. [PubMed: 2399911] [Full Text: https://doi.org/10.1002/ajh.2830350206]

  70. Bare, G. H., Bromberg, P. A., Alben, J. O., Brimhall, B., Jones, R. T., Mintz, S., Rother, I. Altered C-terminal salt bridges in haemoglobin York cause high oxygen affinity. Nature 259: 155-156, 1976. [PubMed: 1246355] [Full Text: https://doi.org/10.1038/259155a0]

  71. Barwick, R. C., Head, C. G., Hih, M. F.-C., Block, S. H., Jones, R. T. Hb T-Cambodia (beta26 (B8) glu-to-lys, beta121 (GH4) glu-to-gln) a new doubly substituted beta globin variant found in a Cambodian family. (Abstract) Blood 66: 68A, 1985.

  72. Barwick, R. C., Jones, R. T., Head, C. G., Shih, M. F.-C., Prchal, J. T., Shih, D. T.-B. Hb Long Island: a hemoglobin variant with a methionyl extension at the NH2 terminus and a prolyl substitution for the normal histidyl residue 2 of the beta chain. Proc. Nat. Acad. Sci. 82: 4602-4605, 1985. [PubMed: 3860812] [Full Text: https://doi.org/10.1073/pnas.82.14.4602]

  73. Bauchwitz, R., Costantini, F. Developmentally distinct effects on human epsilon-, gamma- and delta-globin levels caused by the absence or altered position of the human beta-globin gene in YAC transgenic mice. Hum. Molec. Genet. 9: 561-574, 2000. [PubMed: 10699179] [Full Text: https://doi.org/10.1093/hmg/9.4.561]

  74. Baudin-Chich, V., Wajcman, H., Gombaud-Saintonge, G., Arous, N., Riou, J., Briere, J., Galacteros, F. Hemoglobin Brest (beta127 (H5) gln-to-lys): a new unstable human hemoglobin variant located at the alpha-1/beta-1 interface with specific electrophoretic behavior. Hemoglobin 12: 179-188, 1988. [PubMed: 3384710] [Full Text: https://doi.org/10.3109/03630268808998024]

  75. Baur, E. W., Motulsky, A. G. Hemoglobin Tacoma, a beta-chain variant associated with increased Hb A(2). Humangenetik 1: 621-634, 1965. [PubMed: 5869485]

  76. Baysal, E., Carver, M. F. H. The beta- and delta-thalassemia repository (eighth edition). Hemoglobin 19: 213-236, 1995. [PubMed: 7558879] [Full Text: https://doi.org/10.3109/03630269509036943]

  77. Beldjord, C., Lapoumeroulie, C., Pagnier, J., Benabadji, M., Krishnamoorthy, R., Labie, D., Bank, A. A novel beta-thalassemia gene with a single base mutation in the conserved polypyrimidine sequence at the 3-prime end of IVS-II. Nucleic Acids Res. 16: 4927-4935, 1988. [PubMed: 3387213] [Full Text: https://doi.org/10.1093/nar/16.11.4927]

  78. Bento, M. C., Ribeiro, M. L., Cunha, E., Rebelo, U., Granjo, E., Granado, C., Tamagnini, G. P. Hb Vila Real (beta-36(C2)pro-to-his): a newly discovered high oxygen affinity variant. Hemoglobin 24: 59-63, 2000. [PubMed: 10722117] [Full Text: https://doi.org/10.3109/03630260009002275]

  79. Benz, E. J., Jr., Berman, B. W., Tonkonow, B. L., Coupal, E., Coates, T., Boxer, L. A., Altman, A., Adams, J. G., III. Molecular analysis of the beta-thalassemia phenotype associated with inheritance of hemoglobin E (alpha-2-beta-2(26) glu-to-lys). J. Clin. Invest. 68: 118-126, 1981. [PubMed: 6166632] [Full Text: https://doi.org/10.1172/jci110226]

  80. Benz, E. J., Jr. Genotypes and phenotypes--another lesson from the hemoglobinopathies. New Eng. J. Med. 351: 1490-1492, 2004. Note: Erratum: New Eng. J. Med. 352: 524 only, 2005. [PubMed: 15470211] [Full Text: https://doi.org/10.1056/NEJMp048198]

  81. Benzer, S., Ingram, V. M., Lehmann, H. Three varieties of human haemoglobin D. Nature 182: 852-854, 1958. [PubMed: 13590135] [Full Text: https://doi.org/10.1038/182852a0]

  82. Beresford, C. H., Clegg, J. B., Weatherall, D. J. Haemoglobin Ocho Rios (beta 52 (D3) aspartic acid to alanine): a new beta chain variant of haemoglobin A found in combination with haemoglobin S. J. Med. Genet. 9: 151-153, 1972. [PubMed: 5046622] [Full Text: https://doi.org/10.1136/jmg.9.2.151]

  83. Berglund, S., Linell, F. Fibrosis and carcinoma of the lung in a family with haemoglobin Malmo--anatomic findings. Scand. J. Haemat. 9: 424-432, 1972. [PubMed: 4342316] [Full Text: https://doi.org/10.1111/j.1600-0609.1972.tb00964.x]

  84. Berglund, S. Erythrocytosis associated with haemoglobin Malmo, accompanied by pulmonary changes, occurring in the same family. Scand. J. Haemat. 9: 355-369, 1972. [PubMed: 5073564] [Full Text: https://doi.org/10.1111/j.1600-0609.1972.tb00953.x]

  85. Beris, P., Darbellay, R., Speiser, D., Kirchner, V., Miescher, P. A. De novo initiation codon mutation (ATG-to-ACG) of the beta-globin gene causing beta-thalassemia in a Swiss family. Am. J. Hemat. 42: 248-253, 1993. [PubMed: 8094943] [Full Text: https://doi.org/10.1002/ajh.2830420303]

  86. Beris, P. H., Miescher, P. A., Diaz-Chico, J. C., Hans, I. S., Kutlar, A., Hu, H., Wilson, J. B., Huisman, T. H. J. Inclusion-body beta-thalassemia trait in a Swiss family is caused by an abnormal hemoglobin (Geneva) with an altered and extended beta chain carboxy-terminus due to a modification in codon beta-114. Blood 72: 801-805, 1988. [PubMed: 3401599]

  87. Berlin, G., Wranne, B., Jeppsson, J.-O. Hb Linkoping (beta36 pro-to-thr): a new high oxygen affinity hemoglobin variant found in two families of Finnish origin. Europ. J. Haemat. 39: 452-456, 1987. [PubMed: 3691763] [Full Text: https://doi.org/10.1111/j.1600-0609.1987.tb01455.x]

  88. Berlin, G., Wranne, B. HB Olympia (beta-20(B2)val-to-met) in a Swedish family. Hemoglobin 13: 493-495, 1989. [PubMed: 2599884] [Full Text: https://doi.org/10.3109/03630268908998088]

  89. Bernards, R., Little, P. F. R., Annison, G., Williamson, R., Flavell, R. A. Structure of the human G-gamma-A-gamma-delta-beta-globin gene locus. Proc. Nat. Acad. Sci. 76: 4827-4831, 1979. [PubMed: 291902] [Full Text: https://doi.org/10.1073/pnas.76.10.4827]

  90. Bernini, L. F., Giordano, P. C. Hemoglobin Tilburg: beta 73 (E17) asp-to-gly: a new hemoglobin with reduced oxygen affinity. Biochim. Biophys. Acta 957: 281-285, 1988. [PubMed: 3191145] [Full Text: https://doi.org/10.1016/0167-4838(88)90284-1]

  91. Betke, K., Kleihauer, E., Gehring-Muller, R., Braunitzer, G., Jacobi, J., Schmidt, D. Hb M Hamburg, eine beta-Ketten-Anomalie: beta (63 tyr). Klin. Wschr. 44: 961-966, 1966. [PubMed: 5996551] [Full Text: https://doi.org/10.1007/BF01711469]

  92. Beutler, E., Gelbart, T., Demina, A. Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc. Nat. Acad. Sci. 95: 8170-8174, 1998. [PubMed: 9653159] [Full Text: https://doi.org/10.1073/pnas.95.14.8170]

  93. Beutler, E., Lang, A., Lehmann, H. Hemoglobin Duarte (beta 62 ala-to-pro): a new unstable hemoglobin with increased oxygen affinity. Blood 43: 527-536, 1974. [PubMed: 4361395]

  94. Beuzard, Y., Basset, P., Braconnier, F., El Gammal, H., Martin, L., Oudart, J. L., Thillet, J. Haemoglobin Saki beta 14 leu-to-pro: structure and function. Biochim. Biophys. Acta 393: 182-187, 1975. [PubMed: 237566] [Full Text: https://doi.org/10.1016/0005-2795(75)90229-9]

  95. Beuzard, Y., Courvalin, J. C., Solal, M. C., Garel, M. C., Rosa, J., Brizard, C. P., Gibaud, A. Structural studies of Hb St. Etienne beta 92 (F8) his-to-gln: a new abnormal hemoglobin with loss of beta proximal histidine and absence of heme on the beta chains. FEBS Lett. 27: 76-80, 1972. [PubMed: 11946811] [Full Text: https://doi.org/10.1016/0014-5793(72)80413-7]

  96. Birben, E., Oner, R., Oner, C., Gumruk, F., Gurgey, A., Altay, C. Homozygosity for Hb E-Saskatoon (beta-22(B4)glu-to-lys) in a Turkish patient. Hemoglobin 25: 409-415, 2001. [PubMed: 11791874] [Full Text: https://doi.org/10.1081/hem-100107878]

  97. Bircan, I., Guven, A. G., Yegin, O., Plaseska, D., Wilson, J. B., Ramachandran, M., Huisman, T. H. J. Hb N-Baltimore [beta95(FG2)lys-to-glu] and Hb J-Iran [beta77(EF1)his-to-asp] observed in a Turkish family from Antalya. Hemoglobin 14: 453-457, 1990. [PubMed: 2283300] [Full Text: https://doi.org/10.3109/03630269009032007]

  98. Bird, A. R., Elliot, T. E., Wilson, J. B., Webber, B. B., Kutlar, F., Kutlar, A., Huisman, T. H. J. Hb Boras or beta88 (F4) leu-to-arg in a South African female. Hemoglobin 11: 157-160, 1987. [PubMed: 3623976] [Full Text: https://doi.org/10.3109/03630268709005791]

  99. Bird, A. R., Kent, P., Moores, P. P., Elliott, T. Haemoglobin M-Hyde Park associated with polyagglutinable red blood cells in a South African family. Brit. J. Haemat. 68: 459-464, 1988. [PubMed: 3377987] [Full Text: https://doi.org/10.1111/j.1365-2141.1988.tb04236.x]

  100. Bisse, E., Schlemer, E., Lizama, M., Huaman-Guillen, P., Wieland, H., Adam, G., Molchanova, T. P., Huisman, T. H. J. Hb Strasbourg [beta-23(B5)val-to-asp]: a high oxygen affinity variant observed in a German family. Hemoglobin 22: 69-73, 1998. [PubMed: 9494050] [Full Text: https://doi.org/10.3109/03630269809071519]

  101. Bisse, E., Wieland, H., Ritschel, H. A case of the Hb Regina (beta96 (FG3) leu-to-val) in a German male associated with high oxygen affinity and erythrocytosis. Acta Haemat. 85: 212-216, 1991. [PubMed: 1853685] [Full Text: https://doi.org/10.1159/000204896]

  102. Bisse, E., Zorn, N., Heinrichs, I., Eigel, A., Van Dorsselaer, A., Wieland, H., Kister, J., Marden, M. C. Characterization of a new electrophoretically silent hemoglobin variant: Hb Saale or alpha-2,beta-2 84(EF8)thr-to-ala. J. Biol. Chem. 275: 21380-21384, 2000. [PubMed: 10770934] [Full Text: https://doi.org/10.1074/jbc.M001827200]

  103. Blackwell, R. Q., Huang, J. T. H., Ro, I. H. Hemoglobin variants in Koreans: hemoglobin G (Taegu). Science 158: 1056-1057, 1967. [PubMed: 6054484] [Full Text: https://doi.org/10.1126/science.158.3804.1056]

  104. Blackwell, R. Q., Jim, R. T. S., Liu, C.-S., Weng, M. I., Wang, C.-L., Shih, T.-B. Fast hemoglobin variant found in Hawaiian-Chinese-Caucasian family in Hawaii and a Chinese subject in Taiwan. Vox Sang. 22: 469-473, 1972. [PubMed: 5032420] [Full Text: https://doi.org/10.1111/j.1423-0410.1972.tb03994.x]

  105. Blackwell, R. Q., Liu, C. S., Lie-Injo, L. E., Pribadi, W. Fast hemoglobin variant in Minahassan people of Sulawesi, Chinese and Thais: beta56 gly-to-asp. Am. J. Phys. Anthrop. 32: 147-150, 1970. [PubMed: 5415584] [Full Text: https://doi.org/10.1002/ajpa.1330320118]

  106. Blackwell, R. Q., Liu, C. S., Shih, T. B. Hemoglobin J Kaohsiung: beta 59 lys-to-thr. Biochim. Biophys. Acta 229: 343-348, 1971. [PubMed: 5553980] [Full Text: https://doi.org/10.1016/0005-2795(71)90193-0]

  107. Blackwell, R. Q., Liu, C. S., Wang, C. L. Hemoglobin Siriraj, beta 7 (A4) glu-to-lys, in a Chinese subject in Taiwan. Vox Sang. 23: 433-438, 1972. [PubMed: 5077741] [Full Text: https://doi.org/10.1111/j.1423-0410.1972.tb03831.x]

  108. Blackwell, R. Q., Liu, C. S., Yang, H. J., Wang, C. C., Huang, J. T. H. Hemoglobin variant common to Chinese and North American Indians: beta22 glu-to-ala. Science 161: 381-382, 1968. [PubMed: 5658717] [Full Text: https://doi.org/10.1126/science.161.3839.381]

  109. Blackwell, R. Q., Liu, C. S. The identical structural anomalies of hemoglobin J(Meinung) and J(Korat). Biochem. Biophys. Res. Commun. 24: 732-738, 1966. [PubMed: 5970505] [Full Text: https://doi.org/10.1016/0006-291x(66)90386-x]

  110. Blackwell, R. Q., Liu, C. S. Hemoglobin G Taiwan-Ami: beta 25 gly-to-arg. Biochem. Biophys. Res. Commun. 30: 690-696, 1968. [PubMed: 5642385] [Full Text: https://doi.org/10.1016/0006-291x(68)90568-8]

  111. Blackwell, R. Q., Liu, C.-S., Wang, C.-L. Hemoglobin Ta-Li: beta 83 gly-to-cys. Biochim. Biophys. Acta 243: 467-474, 1971. [PubMed: 5129589]

  112. Blackwell, R. Q., Oemijati, S., Pribadi, W., Weng, M. I., Liu, C. S. Hemoglobin G (Makassar): beta 6 glu-to-ala. Biochim. Biophys. Acta 214: 396-401, 1970. [PubMed: 5509617]

  113. Blackwell, R. Q., Ro, I. H., Liu, C. S., Yang, H. J., Wang, C. C., Huang, J. T. H. Hemoglobin variant found in Koreans, Chinese, and North American Indians: beta 22 glu-to-ala. Am. J. Phys. Anthrop. 30: 389-391, 1969. [PubMed: 5791015] [Full Text: https://doi.org/10.1002/ajpa.1330300307]

  114. Blackwell, R. Q., Shih, T.-B., Wang, C.-L., Liu, C.-S. Hemoglobin G(Hsi-Tsou): beta 79 asp-to-gly. Biochim. Biophys. Acta 257: 49-53, 1972. [PubMed: 5009835] [Full Text: https://doi.org/10.1016/0005-2795(72)90253-x]

  115. Blackwell, R. Q., Yang, H. J., Liu, C. S., Wang, C. C. Structural identification of haemoglobin E in Filipinos. Trop. Geogr. Med. 22: 112-114, 1970. [PubMed: 5435932]

  116. Blackwell, R. Q., Yang, H. J., Wang, C. C. Hemoglobin G (Szuhu): beta 80 asn replaced by lys. Biochim. Biophys. Acta 188: 59-64, 1969. [PubMed: 5820686] [Full Text: https://doi.org/10.1016/0005-2795(69)90045-2]

  117. Blackwell, R. Q., Yang, H. J., Wang, C. C. Hemoglobin G-Taipei: beta 22 glu replaced by gly. Biochim. Biophys. Acta 175: 237-241, 1969. [PubMed: 5778166]

  118. Blackwell, R. Q., Yang, H.-J., Wang, C.-C. Hemoglobin J Taichung: beta129 ala-to-asp. Biochim. Biophys. Acta 194: 1-5, 1969. [PubMed: 5353125]

  119. Blanke, S., Johnsen, A., Wimberley, P. D., Mortensen, H. B. Hemoglobin Hafnia: alpha-2(beta116 (G18) his-to-gln); a new hemoglobin variant mistaken for glycated hemoglobin. Biochim. Biophys. Acta 955: 214-219, 1988. [PubMed: 3395624] [Full Text: https://doi.org/10.1016/0167-4838(88)90195-1]

  120. Blanke, S., Johnsen, A., Wimberley, P. D. HB Volga (beta-27(B9)ala-to-asp), a possible de novo mutation in a Danish person. Hemoglobin 13: 489-491, 1989. [PubMed: 2599883] [Full Text: https://doi.org/10.3109/03630268908998087]

  121. Blibech, R., Mrad, H., Kastally, R., Brissart, M. A., Potron, G., Arous, N., Riou, J., Blouquit, Y., Bardakdjian, J., Lacombe, C., Rosa, J., Galacteros, F. Hemoglobin Beirut (beta 126 val-to-ala) in an Algerian family. Hemoglobin 10: 651-654, 1986. [PubMed: 3557996] [Full Text: https://doi.org/10.3109/03630268609036568]

  122. Blom van Assendelft, G., Hanscombe, O., Grosveld, F., Greaves, D. R. The beta-globin dominant control region activates homologous and heterologous promoters in a tissue-specific manner. Cell 56: 969-977, 1989. [PubMed: 2924354] [Full Text: https://doi.org/10.1016/0092-8674(89)90630-2]

  123. Blouquit, Y., Arous, N., Lena, D., Delanoe-Garin, J., Lacombe, C., Bardakdjian, J., Vovan, L., Orsini, A., Rosa, J., Galacteros, F. Hb Marseille (beta N methionyl-2 (NA-2) his-to-pro): a new beta chain variant having an extended N-terminus. FEBS Lett. 178: 315-318, 1984. [PubMed: 6548977] [Full Text: https://doi.org/10.1016/0014-5793(84)80624-9]

  124. Blouquit, Y., Arous, N., Machado, P. E. A., Garel, M. C. Hb Henri Mondor: beta 26(B8) glu-to-val: a variant with a substitution localized at the same position as that of Hb E beta 26 glu-to-lys. FEBS Lett. 72: 5-7, 1976. [PubMed: 1001469] [Full Text: https://doi.org/10.1016/0014-5793(76)80800-9]

  125. Blouquit, Y., Bardakdjian, J., Lena-Russo, D., Arous, N., Perrimond, H., Orsini, A., Rosa, J., Galacteros, F. HB Bruxelles: beta-41 or 42(C7 or CD1)phe deleted. Hemoglobin 13: 465-474, 1989. [PubMed: 2599881] [Full Text: https://doi.org/10.3109/03630268908998085]

  126. Blouquit, Y., Braconnier, F., Cohen-Solal, M., Foldi, J., Arous, N., Ankri, A., Binet, J. L., Rosa, J. Hemoglobin Pitie-Salpetriere beta 34 (B16) val-to-phe: a new high oxygen affinity variant associated with familial erythrocytosis. Biochim. Biophys. Acta 624: 473-478, 1980. [PubMed: 7417488] [Full Text: https://doi.org/10.1016/0005-2795(80)90088-4]

  127. Blouquit, Y., Braconnier, F., Galacteros, F., Arous, N., Soria, J., Zittoun, R., Rosa, J. Hemoglobin Hotel-Dieu, beta-99 asp-to-gly (G1): a new abnormal hemoglobin with high oxygen affinity. Hemoglobin 5: 19-31, 1981. [PubMed: 7204092] [Full Text: https://doi.org/10.3109/03630268108996908]

  128. Blouquit, Y., Delanoe-Garin, J., Lacombe, C., Arous, N., Cayre, Y., Peduzzi, J., Braconnier, F., Galacteros, F. Structural study of hemoglobin Hazebrouck, beta38(C4)thr-to-pro: a new abnormal hemoglobin with instability and low oxygen affinity. FEBS Lett. 172: 155-158, 1984. Note: Abstract: Hemoglobin 9: 106-107, 1985. [PubMed: 6430717] [Full Text: https://doi.org/10.1016/0014-5793(84)81116-3]

  129. Blouquit, Y., Lena-Russo, D., Delanoe, J., Arous, N., Bardakjian, J., Lacombe, C., Vovan, L., Orsini, A., Rosa, J., Galacteros, F. Hb Marseille beta-1(A1)NH2-met, 2(A2)his-to-3(A3)pro: first variant having a N-terminal elongated beta chain. (Abstract) Hemoglobin 9: 107-108, 1985.

  130. Boehm, C. D., Dowling, C. E., Antonarakis, S. E., Honig, G. R., Kazazian, H. H., Jr. Evidence supporting a single origin of the beta(C)-globin gene in blacks. Am. J. Hum. Genet. 37: 771-777, 1985. [PubMed: 9556665]

  131. Boehm, C. D., Dowling, C. E., Waber, P. G., Giardina, P. J. V., Kazazian, H. H., Jr. Use of oligonucleotide hybridization in the characterization of a beta-zero-thalassemia gene (beta37 TGG-to-TGA) in a Saudi Arabian family. Blood 67: 1185-1188, 1986. Note: Erratum: Blood 68: 323 only, 1986. [PubMed: 3006832]

  132. Bogoevski, P., Efremov, G. D., Kezic, J., Lam, H., Wilson, J. B., Huisman, T. H. J. Hb Sabine or beta 91(F7) leu-to-pro in a Yugoslavian boy. Hemoglobin 7: 195-200, 1983. [PubMed: 6671906]

  133. Boi, S., Hendy, J., Goodall, I., Gilbert, A., Fleming, P., Hughes, W. G. First report of HB Long Island-Marseille in Australia--a chance discovery. Hemoglobin 13: 515-520, 1989. [PubMed: 2599888] [Full Text: https://doi.org/10.3109/03630268908998092]

  134. Boissel, J. P., Wajcman, H., Fabritius, H., Cabannes, R., Labie, D. Application of high-performance liquid chromatography to abnormal hemoglobin studies. Characterization of hemoglobin D in Ivory Coast and description of a new variant, Hb Cocody (beta 21 asp leads to asn). Biochim. Biophys. Acta 670: 203-206, 1981. [PubMed: 6271242] [Full Text: https://doi.org/10.1016/0005-2795(81)90010-6]

  135. Boissel, J. P., Wajcman, H., Labie, D., Fabritius, H., Cabannes, R. Hb J Daloa (beta 57 (E1) asn replaced by asp): a new variant found in Ivory Coast. Hemoglobin 6: 433-437, 1982. [PubMed: 6292136] [Full Text: https://doi.org/10.3109/03630268208996952]

  136. Boissel, J.-P., Kasper, T. J., Shah, S. C., Malone, J. I., Bunn, H. F. Amino-terminal processing of proteins: hemoglobin South Florida, a variant with retention of initiator methionine and N(alpha)-acetylation. Proc. Nat. Acad. Sci. 82: 8448-8452, 1985. [PubMed: 3866233] [Full Text: https://doi.org/10.1073/pnas.82.24.8448]

  137. Bonaventura, C., Cashon, R., Bonaventura, J., Perutz, M., Fermi, G., Shih, D. T.-B. Involvement of the distal histidine in the low affinity exhibited by Hb Chico (lys-beta66-to-thr) and its isolated beta chains. J. Biol. Chem. 266: 23033-23040, 1991. [PubMed: 1744099]

  138. Bonaventura, J., Riggs, A. Polymerization of hemoglobins of mouse and man: structural basis. Science 158: 800-802, 1967. [PubMed: 6048124] [Full Text: https://doi.org/10.1126/science.158.3802.800-a]

  139. Bonaventura, J., Riggs, A. Hemoglobin Kansas, a human hemoglobin with a neutral amino acid substitution and an abnormal oxygen equilibrium. J. Biol. Chem. 243: 980-991, 1968. [PubMed: 5640981]

  140. Bookchin, R. M., Davis, R. P., Ranney, H. M. Clinical features of hemoglobin C(Harlem), a new sickling hemoglobin variant. Ann. Intern. Med. 68: 8-18, 1968.

  141. Bookchin, R. M., Nagel, R. L., Ranney, H. M., Jacobs, A. S. Hemoglobin C (Harlem): a sickling variant containing amino acid substitutions in two residues of the beta-polypeptide chain. Biochem. Biophys. Res. Commun. 23: 122-127, 1966. [PubMed: 5928902] [Full Text: https://doi.org/10.1016/0006-291x(66)90515-8]

  142. Bookchin, R. M., Nagel, R. L., Ranney, H. M. The effect of beta 73 asn on the interactions of sickling hemoglobins. Biochim. Biophys. Acta 221: 373-375, 1970. [PubMed: 5490239] [Full Text: https://doi.org/10.1016/0005-2795(70)90279-5]

  143. Bottardi, S., Bourgoin, V., Pierre-Charles, N., Milot, E. Onset and inheritance of abnormal epigenetic regulation in hematopoietic cells. Hum. Molec. Genet. 14: 493-502, 2005. [PubMed: 15615768] [Full Text: https://doi.org/10.1093/hmg/ddi046]

  144. Bouhass, R., Aguercif, M., Trabuchet, G., Godet, J. A new mutation at IVS1 nt 2(T-to-A), in beta-thalassemia from Algeria. (Letter) Blood 76: 1054-1055, 1990. [PubMed: 2393712]

  145. Boulton, F. E., Huntsman, R. G., Lehmann, H., Lorkin, P., Romero-Herrera, A. E. Myoglobin variants. (Abstract) Biochem. J. 118: 39P, 1970.

  146. Bowman, B. H., Barnett, D. R., Hite, R. Hemoglobin G (Coushatta): a beta variant with a delta-like substitution. Biochem. Biophys. Res. Commun. 26: 466-470, 1967. [PubMed: 6033745] [Full Text: https://doi.org/10.1016/0006-291x(67)90570-0]

  147. Bowman, B. H., Moreland, H., Schneider, R. G. A new haemoglobin variant (G-Galveston). Nature 193: 1298-1300, 1962.

  148. Bowman, B. H., Oliver, C. P., Barnett, D. R., Cunningham, J. E., Schneider, R. G. Chemical characterization of three hemoglobins G. Blood 23: 193-199, 1964.

  149. Bowman, R., Ingram, V. M. Abnormal human haemoglobin. VII. The comparison of normal human haemoglobin and haemoglobin D (Chicago). Biochim. Biophys. Acta 53: 569-573, 1961. [PubMed: 13872094] [Full Text: https://doi.org/10.1016/0006-3002(61)90216-5]

  150. Boyer, S. H., Charache, S., Fairbanks, V. F., Maldonado, J. E., Noyes, A., Gayle, E. E. Hemoglobin Malmo beta-97 (FG-4) histidine to glutamine: a cause of polycythemia. J. Clin. Invest. 51: 666-676, 1972. [PubMed: 5011106] [Full Text: https://doi.org/10.1172/JCI106855]

  151. Boyer, S. H., Rucknagel, D. L., Weatherall, D. J., Watson-Williams, E. J. Further evidence for linkage between the beta and gamma loci governing human hemoglobin and the population dynamics of linked genes. Am. J. Hum. Genet. 15: 438-448, 1963. [PubMed: 14097238]

  152. Brabec, V., Indrak, K., Fortova, H., Suttnar, J., Blazek, B., Cermak, J., Divoky, V., Veprekova, L., Zeman, J. Hb Nottingham or beta 98 (FG5) val-to-gly in a Czech child. Ann. Hemat. 69: 93-95, 1994. [PubMed: 8080886] [Full Text: https://doi.org/10.1007/BF01698489]

  153. Bradley, T. B., Jr., Wohl, R. C., Rieder, R. F. Hemoglobin Gun Hill: deletion of five amino acid residues and impaired heme-globin binding. Science 157: 1581-1583, 1967. [PubMed: 6038175] [Full Text: https://doi.org/10.1126/science.157.3796.1581]

  154. Bradley, T. B., Wohl, R. C., Murphy, S. B., Oski, F. A., Bunn, H. F. Properties of hemoglobin Bryn Mawr, beta85 phe-to-ser, a new spontaneous mutation producing an unstable hemoglobin with high oxygen affinity. (Abstract) Blood 40: 947, 1972.

  155. Bradley, T. B., Wohl, R. C., Petz, L. D., Perkins, H. A., Reynolds, R. D. Possible gonadal mosaicism in a family with hemoglobin Koln. Johns Hopkins Med. J. 146: 236-240, 1980. [PubMed: 7382247]

  156. Brancati, C., Caracciolo, M., Bria, M., Bisconte, M. G., Qualtieri, A. HB G-San Jose homozygosis in a Calabrian family. Hemoglobin 13: 497-503, 1989. [PubMed: 2599885] [Full Text: https://doi.org/10.3109/03630268908998089]

  157. Bratu, V., Lorkin, P. A., Lehmann, H., Predescu, C. Haemoglobin Bucuresti (beta 42 (CD1) phe-to-leu), a cause of unstable haemoglobin haemolytic anaemia. Biochim. Biophys. Acta 251: 1-6, 1971. [PubMed: 5133275] [Full Text: https://doi.org/10.1016/0005-2795(71)90051-1]

  158. Brennan, S. O., Arnold, B., Fleming, P., Carrell, R. W. A new unstable haemoglobin, beta 134: val-to-glu. Proc. New Zeal. Med. J. 85: 398-399, 1977.

  159. Brennan, S. O., Jones, K. O., Crethar, L., Arnold, B. J., Fleming, P. J., Winterbourn, C. C. Haemoglobin North Shore, beta134 val replaced by glu, a new unstable haemoglobin. Biochim. Biophys. Acta 494: 403-407, 1977. [PubMed: 199272] [Full Text: https://doi.org/10.1016/0005-2795(77)90169-6]

  160. Brennan, S. O., Potter, H. C., Kubala, L. M., Carnoutsos, S. A., Ferguson, M. M. Hb Canterbury (beta-112(G14)cys-to-phe): a new, mildly unstable variant. Hemoglobin 26: 67-69, 2002. [PubMed: 11939514] [Full Text: https://doi.org/10.1081/hem-120002942]

  161. Brennan, S. O., Shaw, J., Allen, J., George, P. M. Beta-141 leu is not deleted in the unstable haemoglobin Atlanta-Coventry but is replaced by a novel amino acid of mass 129 daltons. Brit. J. Haemat. 81: 99-103, 1992. [PubMed: 1520632] [Full Text: https://doi.org/10.1111/j.1365-2141.1992.tb08179.x]

  162. Brennan, S. O., Wells, R. M., Smith, H., Carrell, R. W. Hemoglobin Brisbane: beta68 leu-to-his: a new high oxygen affinity variant. Hemoglobin 5: 325-335, 1981. [PubMed: 6166590] [Full Text: https://doi.org/10.3109/03630268108991807]

  163. Brennan, S. O., Williamson, D., Symmans, W. A., Carrell, R. W. Two unstable hemoglobins in one individual: Hb Atlanta (beta75 leu-to-pro) and Hb Coventry (beta 141 leu deleted). Hemoglobin 7: 303-312, 1983. [PubMed: 6618886] [Full Text: https://doi.org/10.3109/03630268309052711]

  164. Brennan, S. O., Williamson, D., Symmans, W. A., Carrell, R. W. Two de novo mutations in one beta globin chain: hemoglobin Atlanta-Coventry, beta75 leu-to-pro and beta141 deleted. Hemoglobin 10: 225-237, 1986. [PubMed: 3710819] [Full Text: https://doi.org/10.3109/03630268609042844]

  165. Brennan, S. O., Williamson, D., Whisson, M. E., Carrell, R. W. Hemoglobin Palmerston North, beta23 (B5) val-to-phe: a new variant identified in a patient with polycythemia. Hemoglobin 6: 569-575, 1982. [PubMed: 7161106] [Full Text: https://doi.org/10.3109/03630268209046450]

  166. Brimhall, B., Jones, R. T., Baur, E. W., Motulsky, A. G. Structural characterization of hemoglobin Tacoma. Biochemistry 8: 2125-2129, 1969. [PubMed: 5785231] [Full Text: https://doi.org/10.1021/bi00833a051]

  167. Brimhall, B., Jones, T. T., Schneider, R. G., Hosty, T. S., Tomlin, G., Atkins, R. Two new hemoglobins: hemoglobin Alabama (beta 39 (C5) gln-to-lys) and hemoglobin Montgomery (alpha 48 (CD6) leu-to-arg). Biochim. Biophys. Acta 379: 28-32, 1975. [PubMed: 1115799]

  168. Brittenham, G., Lozoff, B., Harris, J. W., Nayudu, N. V. S., Gravely, M., Wilson, J. B., Lam, H., Huisman, T. H. J. Hemoglobin Hofu or beta (126 (H4) val-to-glu) found in combination with hemoglobin S. Hemoglobin 2: 541-549, 1978. [PubMed: 750554] [Full Text: https://doi.org/10.3109/03630267809005355]

  169. Bromberg, P. A., Alben, J. O., Bare, G. H., Balcerzak, S. P., Jones, R. T., Brimhall, B., Padilla, F. High oxygen affinity variant of haemoglobin Little Rock with unique properties. Nature N.B. 243: 177-179, 1973. [PubMed: 4514629] [Full Text: https://doi.org/10.1038/newbio243177a0]

  170. Brown, W. J., Niazi, G. A., Jayalakshmi, M., Abraham, E. C., Huisman, T. H. J. Hemoglobin Athens-Georgia, or beta40 (C6) arg-to-lys, a hemoglobin variant with an increased oxygen affinity. Biochim. Biophys. Acta 439: 70-76, 1976. [PubMed: 8114] [Full Text: https://doi.org/10.1016/0005-2795(76)90162-8]

  171. Broxson, E. H., Hine, T. K., Moo-Penn, W. F. Hb Muskegon [beta-83 (EF7) gly-to-arg]: a new variant found in a family from the U.S. Hemoglobin 17: 85-86, 1993. [PubMed: 8454474] [Full Text: https://doi.org/10.3109/03630269308998889]

  172. Buckett, L. B., Sharma, V. S., Pisciotta, A. V., Ranney, H., Bruckheimer, P. Hemoglobin Mequon beta 41 (C7) phenylalanine-to-tyrosine. (Abstract) Clin. Res. 22: 176A, 1974.

  173. Budge, L. J., Bradley, T. B., Graham, J. L. Hemoglobin Riyadh in a Mexican American family of Spanish ancestry. Hemoglobin 1: 283-295, 1977. [PubMed: 893129] [Full Text: https://doi.org/10.3109/03630267709003410]

  174. Bundgaard, J. R., Bjerrum, O. W., Tybjaerg-Hansen, A. A new variant with two amino acid substitutions: Hb S-Cameroon [beta-6(A3)glu-to-val; beta-90(F6)glu-to-lys]. Hemoglobin 28: 131-135, 2004. [PubMed: 15182055] [Full Text: https://doi.org/10.1081/hem-120035918]

  175. Bunn, H. F., Altman, A. J., Stangland, K., Firshein, S. I., Forget, B., Schmidt, G. J., Jones, R. T. Hemoglobins Aida (alpha 64 asp-to-asn) and D-Los Angeles (beta 121 glu-to-gln) in an Asian-Indian family. Hemoglobin 2: 531-540, 1978. [PubMed: 750553] [Full Text: https://doi.org/10.3109/03630267809005354]

  176. Bunn, H. F., Bradley, T. B., Davis, W. E., Drysdale, J. W., Burke, J. F., Beck, W. S., Laver, M. B. Structural and functional studies on hemoglobin Bethesda (beta 145 his), a variant associated with compensatory erythrocytosis. J. Clin. Invest. 51: 2299-2309, 1972. [PubMed: 4639015] [Full Text: https://doi.org/10.1172/JCI107040]

  177. Bunn, H. F., Schmidt, G. J., Haney, D. N., Dluhy, R. G. Hemoglobin Cranston, an unstable variant having an elongated beta chain due to nonhomologous crossover between two normal beta chain genes. Proc. Nat. Acad. Sci. 72: 3609-3613, 1975. [PubMed: 1059149] [Full Text: https://doi.org/10.1073/pnas.72.9.3609]

  178. Bursaux, E., Blouquit, Y., Poyart, C., Rosa, J., Arous, N., Bohn, B. Hemoglobin Ty Gard (beta124 pro-to-gln): a stable high O2 affinity variant at the alpha-1-beta-1 contact. FEBS Lett. 88: 155-159, 1978. [PubMed: 639985] [Full Text: https://doi.org/10.1016/0014-5793(78)80630-9]

  179. Butler, W. M., Spratling, L., Kark, J. A., Schoomaker, E. B. Hemoglobin Osler: report of a family with exercise studies before and after phlebotomy. Am. J. Hemat. 13: 293-301, 1982. [PubMed: 7158624] [Full Text: https://doi.org/10.1002/ajh.2830130404]

  180. Cai, S. P., Chang, C. A., Zhang, J. Z., Saiki, R. K., Erlich, H. A., Kan, Y. W. Rapid prenatal diagnosis of beta-thalassemia using DNA amplification and nonradioactive probes. Blood 73: 372-374, 1989. [PubMed: 2917180]

  181. Cai, S.-P., Kan, Y. W. Identification of the multiple beta-thalassemia mutations by denaturing gradient gel electrophoresis. J. Clin. Invest. 85: 550-553, 1990. [PubMed: 2298920] [Full Text: https://doi.org/10.1172/JCI114471]

  182. Cai, S.-P., Zhang, J.-Z., Doherty, M., Kan, Y. W. A new TATA box mutation detected at prenatal diagnosis for beta-thalassemia. Am. J. Hum. Genet. 45: 112-114, 1989. [PubMed: 2741940]

  183. Cai Yin Lin, Wang He Be, Yang Xue Yong, Liu Zheng Hong, Ao Zhong Fang, Gong Dao Hua, Ma Jian Ping, Wang Min Juan, Ma Da Rong, Xu Yu Qing, Chen En Hui. A new fast-moving hemoglobin variant, Hb J Luhe beta8 (A5) lys-to-glutamine. Chinese Hemat. J. 3: 263-265, 1982.

  184. Camaschella, C., Bertero, M. T., Serra, A., Dall'Acqua, M., Gasparini, P., Trento, M., Vettore, L., Perona, G., Saglio, G., Mazza, U. A benign form of thalassaemia intermedia may be determined by the interaction of triplicated alpha locus and heterozygous beta-thalassaemia. Brit. J. Haemat. 66: 103-107, 1987. [PubMed: 3593644] [Full Text: https://doi.org/10.1111/j.1365-2141.1987.tb06897.x]

  185. Camaschella, C., Serra, A., Gottardi, E., Alfarano, A., Revello, D., Mazza, U., Saglio, G. A new hereditary persistence of fetal hemoglobin deletion has the breakpoint within the 3-prime beta-globin gene enhancer. Blood 75: 1000-1005, 1990. [PubMed: 1689188]

  186. Camaschella, C., Serra, A., Saglio, G., Bertero, M. T., Mazza, U., Terzoli, S., Brambati, B., Cremonesi, L., Travis, M., Ferrari, M. Meiotic recombination in the beta-globin gene cluster causing an error in prenatal diagnosis of beta-thalassaemia. J. Med. Genet. 25: 307-310, 1988. [PubMed: 2898535] [Full Text: https://doi.org/10.1136/jmg.25.5.307]

  187. Cao, A., Furbetta, M., Galanello, R., Melis, M. A., Angius, A., Ximenes, A., Rosatelli, C., Ruggeri, R., Addis, M., Tuveri, T., Falchi, A. M., Paglietti, E., Scalas, M. T. Prevention of homozygous beta-thalassemia by carrier screening and prenatal diagnosis in Sardinia. Am. J. Hum. Genet. 33: 592-605, 1981. [PubMed: 7258188]

  188. Carbone, V., Salzano, A. M., Pagano, L., Buffardi, S., De Rosa, C., Pucci, P. Identification of Hb Villejuif (beta-123(H1)thr-to-ile) in Southern Italy. Hemoglobin 25: 67-78, 2001. [PubMed: 11300351] [Full Text: https://doi.org/10.1081/hem-100103071]

  189. Carbone, V., Salzano, A. M., Pagano, L., Viola, A., Buffardi, S., De Rosa, C., Pucci, P. Hb Rainier [beta-145(HC2)tyr to cys] in Italy. Characterization of the amino acid substitution and the DNA mutation. Hemoglobin 23: 111-124, 1999. [PubMed: 10335979] [Full Text: https://doi.org/10.3109/03630269908996156]

  190. Carcassi, U. E. F., Pintus, A., Gravely, M. E., Huisman, T. H. J. Beta-zero-thalassemia in association with Hb Leslie (beta 131GLN to 0) in a Sardinian family. Hemoglobin 4: 195-200, 1980. [PubMed: 7390864]

  191. Carrell, R. W., Lehmann, H., Hutchison, H. E. Haemoglobin Koln (beta-98 valine to methionine): an unstable protein causing inclusion body anaemia. Nature 210: 915-917, 1966. [PubMed: 5960324] [Full Text: https://doi.org/10.1038/210915a0]

  192. Carrell, R. W., Lehmann, H., Lorkin, P. A., Raik, E., Hunter, E. Haemoglobin Sydney: beta 67 (E 11) valine to alanine: an emerging pattern of unstable haemoglobins. Nature 215: 626-628, 1967. [PubMed: 6050213] [Full Text: https://doi.org/10.1038/215626a0]

  193. Carrell, R. W. Personal Communication. Christchurch, New Zealand 1970.

  194. Carver, M. F. H., Kutlar, A. International Hemoglobin Information Center: variant list. Hemoglobin 19: 37-149, 1995. [PubMed: 7615401]

  195. Casey, R., Kynoch, P. A., Lang, A., Lehmann, H., Nozari, G., Shinton, N. K. Double heterozygosity for two unstable haemoglobins: Hb Sydney (beta67(E11) val-to-ala) and Hb Coventry (beta141(H19) leu deleted). Brit. J. Haemat. 38: 195-209, 1978. [PubMed: 638069] [Full Text: https://doi.org/10.1111/j.1365-2141.1978.tb01036.x]

  196. Casey, R., Lang, A., Lehmann, H., Shinton, N. K. Double heterozygosity for two unstable hemoglobins: Hb Sydney (beta-67 (E11) val-to-ala) and Hb Coventry (beta-141 (H19) leu deleted). Brit. J. Haemat. 33: 143-144, 1976.

  197. Castagnola, M., Cassiano, L., Rossetti, D. V., Marucci, L., Ferro, A., Scarano, C., Monaco, M., Celozzi, A. M. Hb K-Ibadan [beta46(CD5)gly-to-glu] in an Italian family. Hemoglobin 14: 647-651, 1990. [PubMed: 1983219]

  198. Cathie, I. A. B. Apparent idiopathic Heinz body anaemia. Great Ormond Street J. 2: 43-48, 1952.

  199. Cepreganova, B., Wilson, J. B., Huisman, T. H. J., Hume, H. A. Hb Nottingham or beta98(FG5)val-to-gly observed as a de novo mutation in a Canadian child. Hemoglobin 16: 77-79, 1992. [PubMed: 1634365] [Full Text: https://doi.org/10.3109/03630269209005679]

  200. Chaganti, R. S. K., Jhanwar, S. C., Antonarakis, S. E., Hayward, W. S. Germ-line chromosomal localization of genes in chromosome 11p linkage: parathyroid hormone, beta-globin, c-Ha-ras-1, and insulin. Somat. Cell Molec. Genet. 11: 197-202, 1985. [PubMed: 3885418] [Full Text: https://doi.org/10.1007/BF01534708]

  201. Chakravarti, A., Buetow, K. H., Antonarakis, S. E., Waber, P. G., Boehm, C. D., Kazazian, H. H. Nonuniform recombination within the human beta-globin gene cluster. Am. J. Hum. Genet. 36: 1239-1258, 1984. [PubMed: 6097112]

  202. Chan, V., Chan, T. K., Kan, Y. W., Todd, D. A novel beta-thalassemia frameshift mutation (codon 14/15) detectable by direct visualization of abnormal restriction fragment in amplified genomic DNA. Blood 72: 1420-1423, 1988. [PubMed: 2901867]

  203. Chang, J. C., Alberti, A., Kan, Y. W. A beta-thalassemia lesion abolishes the same MstII site as the sickle mutation. Nucleic Acids Res. 11: 7789-7794, 1983. [PubMed: 6316272] [Full Text: https://doi.org/10.1093/nar/11.22.7789]

  204. Chang, J. C., Kan, Y. W. Beta-0-thalassemia, a nonsense mutation in man. Proc. Nat. Acad. Sci. 76: 2886-2889, 1979. [PubMed: 88735] [Full Text: https://doi.org/10.1073/pnas.76.6.2886]

  205. Chang, J. C., Kan, Y. W. Antenatal diagnosis of sickle cell anaemia by direct analysis of the sickle mutation. Lancet 318: 1127-1129, 1981. Note: Originally Volume II. [PubMed: 6118575] [Full Text: https://doi.org/10.1016/s0140-6736(81)90584-5]

  206. Chang, J. C., Kan, Y. W. A sensitive new prenatal test for sickle-cell anemia. New Eng. J. Med. 307: 30-32, 1982. [PubMed: 6176866] [Full Text: https://doi.org/10.1056/NEJM198207013070105]

  207. Chang, J. C., Kan, Y. W. A sensitive test for prenatal diagnosis of sickle cell anemia: direct analysis of amniocyte DNA with MstII. Trans. Assoc. Am. Phys. 95: 71-78, 1982. [PubMed: 6304979]

  208. Chang, J. C., Temple, G. F., Trecartin, R. F., Kan, Y. W. Beta-zero thalassemia: a nonsense mutation in man, and its correction in vitro. (Abstract) Clin. Res. 27: 457A, 1979.

  209. Chang, J.-G., Lee, L.-S., Chen, P.-H., Chen, Y.-H. Hb Kaohsiung or New York: a T-to-A substitution at codon 113 of the beta-globin chain creates an Alu I cutting site. Hemoglobin 16: 123-125, 1992. [PubMed: 1634358] [Full Text: https://doi.org/10.3109/03630269209005686]

  210. Chang, J.-G., Yang, T.-Y., Perng, L.-I., Wang, J.-C., Tsan, K.-W. Hb Koln [beta-98(FG5)val to met]: the first case found in a Chinese family. Hemoglobin 22: 535-536, 1998. [PubMed: 9859938] [Full Text: https://doi.org/10.3109/03630269809071552]

  211. Chang, J.-G., Yang, T.-Y., Perng, L.-I., Wang, N. M., Peng, C.-T., Tsai, C.-H. Hb Siriraj: a G-to-A substitution at codon 7 of the beta-globin chain creates an MboII cutting site. Hemoglobin 23: 197-199, 1999. [PubMed: 10335989] [Full Text: https://doi.org/10.3109/03630269908996166]

  212. Charache, S., Achuff, S., Winslow, R., Kazazian, H. Oxygen transport in a woman with hemoglobin Hope/beta-plus-thalassemia. J. Lab. Clin. Med. 93: 316-320, 1979. [PubMed: 429843]

  213. Charache, S., Brimhall, B., Jones, R. T. Polycythemia produced by hemoglobin Osler (beta 145 (HC2) tyr-to-asp). Johns Hopkins Med. J. 136: 132-136, 1975. [PubMed: 1117598]

  214. Charache, S., Brimhall, B., Milner, P., Cobb, L. Hemoglobin Okaloosa (beta 48 (CD7) leucine to arginine) an unstable variant with low oxygen affinity. J. Clin. Invest. 52: 2858-2864, 1973. [PubMed: 4748512] [Full Text: https://doi.org/10.1172/JCI107482]

  215. Charache, S., Fox, J., McCurdy, P., Kazazian, H., Jr., Winslow, R. Post-synthetic deamidation of hemoglobin Providence (beta 82 lys-to-asn, asp) and its effect on oxygen transport. J. Clin. Invest. 59: 652-658, 1977. [PubMed: 14973] [Full Text: https://doi.org/10.1172/JCI108683]

  216. Charache, S., Jacobson, R., Brimhall, B., Murphy, E. A., Hathaway, P., Winslow, R., Jones, R., Rath, C. Hb Potomac (beta 101 glu-to-asp): speculations on placental oxygen transport in carriers of high-affinity hemoglobins. Blood 51: 331-338, 1978. [PubMed: 563749]

  217. Charache, S., Zinkham, W. H., Dickerman, J. D., Brimhall, B., Dover, G. J. Hemoglobin SC, SS-G(Philadelphia) and SO(Arab) diseases: diagnostic importance of an integrative analysis of clinical, hematologic and electrophoretic findings. Am. J. Med. 62: 439-446, 1977. [PubMed: 842562] [Full Text: https://doi.org/10.1016/0002-9343(77)90844-0]

  218. Chebloune, Y., Pagnier, J., Trabuchet, G., Faure, C., Verdier, G., Labie, D., Nigon, V. Structural analysis of the 5-prime flanking region of the beta-globin gene in African sickle cell anemia patients: further evidence for three origins of the sickle cell mutation in Africa. Proc. Nat. Acad. Sci. 85: 4431-4435, 1988. [PubMed: 2898142] [Full Text: https://doi.org/10.1073/pnas.85.12.4431]

  219. Chehab, F. F., Honig, G. R., Kan, Y. W. Spontaneous mutation in beta-thalassaemia producing the same nucleotide substitution as that in a common hereditary form. Lancet 327: 3-5, 1986. Note: Originally Volume I. [PubMed: 2867271] [Full Text: https://doi.org/10.1016/s0140-6736(86)91892-1]

  220. Chehab, F. F., Winterhalter, K. H., Kan, Y. W. Characterization of a spontaneous mutation in beta-thalassemia associated with advanced paternal age. Blood 74: 852-854, 1989. [PubMed: 2665856]

  221. Chen, S. S., Webber, B. B., Wilson, J. B., Huisman, T. H. J. Hb Gainesville-GA or beta46(CD5)gly-to-arg. Hemoglobin 9: 179-181, 1985. [PubMed: 3839773] [Full Text: https://doi.org/10.3109/03630268508997000]

  222. Chen, S. S., Wilson, J. B., Webber, B. B., Kutlar, A., Huisman, T. H. J. Hb G-Copenhagen or beta47(CD6)asp-to-asn observed in a black newborn. Hemoglobin 9: 405-408, 1985. [PubMed: 4077558] [Full Text: https://doi.org/10.3109/03630268508997016]

  223. Chen-Marotel, J., Braconnier, F., Blouquit, Y., Martin-Caburi, J., Kammerer, J., Rosa, J. Hemoglobin Bougardirey-Mali beta 119 (GH2) gly-to-val, an electrophoretically silent variant migrating in isoelectrofocusing as Hb F. Hemoglobin 3: 253-262, 1979. [PubMed: 500370] [Full Text: https://doi.org/10.3109/03630267908996901]

  224. Cheng, T.-C., Orkin, S. H., Antonarakis, S. E., Potter, M. J., Sexton, J. P., Markham, A. F., Giardina, P. J. V., Li, A., Kazazian, H. H., Jr. Beta-thalassemia in Chinese: use of in vivo RNA analysis and oligonucleotide hybridization in systematic characterization of molecular defects. Proc. Nat. Acad. Sci. 81: 2821-2825, 1984. [PubMed: 6585831] [Full Text: https://doi.org/10.1073/pnas.81.9.2821]

  225. Chernoff, A. I., Perillie, P. E. The amino acid composition of hemoglobin B New Haven-2 or HgB N (New Haven). Biochem. Biophys. Res. Commun. 16: 368-372, 1964. [PubMed: 5872025] [Full Text: https://doi.org/10.1016/0006-291x(64)90042-7]

  226. Chernoff, A. I., Pettit, N. M. The amino acid composition of hemoglobin. III. A qualitative method for identifying abnormalities of the polypeptide chains of hemoglobin. Blood 24: 750-756, 1964. [PubMed: 14235356]

  227. Chernoff, A. I., Weichselbaum, T. E. A microhemolyzing technic for preparing solutions of hemoglobin for paper electrophoretic analysis. Am. J. Clin. Path. 30: 120-125, 1958. [PubMed: 13559175] [Full Text: https://doi.org/10.1093/ajcp/30.2.120]

  228. Chiancone, E., Norne, J. E., Bonaventura, J., Bonaventura, C., Forsen, S. Nuclear magnetic resonance quadrupole relaxation study of chloride binding to hemoglobin Abruzzo (beta 143 his-to-arg). Biochim. Biophys. Acta 336: 403-406, 1974.

  229. Chibani, J., Vidaud, M., Duquesnoy, P., Berge-Lefranc, J. L., Pirastu, M., Ellouze, F., Rosa, J., Goossens, M. The peculiar spectrum of beta-thalassemia genes in Tunisia. Hum. Genet. 78: 190-192, 1988. [PubMed: 3422218] [Full Text: https://doi.org/10.1007/BF00278196]

  230. Chifu, Y., Nakashima, H., Hara, H., Yokota, E., Imamura, T. Beta-thalassemia major resulting from a compound heterozygosity for the beta-globin gene mutation: further evidence for multiple origin and migration of the thalassemia gene. Hum. Genet. 89: 343-346, 1992. [PubMed: 1351038] [Full Text: https://doi.org/10.1007/BF00220556]

  231. Chiu, R. W. K., Lau, T. K., Leung, T. N., Chow, K. C. K., Chui, D. H. K., Lo, Y. M. D. Prenatal exclusion of beta thalassaemia major by examination of maternal plasma. Lancet 360: 998-1000, 2002. [PubMed: 12383672] [Full Text: https://doi.org/10.1016/s0140-6736(02)11086-5]

  232. Cholera, R., Brittain, N. J., Gillrie, M. R., Lopera-Mesa, T. M., Diakite, S. A. S., Arie, T., Krause, M. A., Guindo, A., Tubman, A., Fujioka, H., Diallo, D. A., Doumbo, O. K., Ho, M., Wellems, T. E., Fairhurst, R. M. Impaired cytoadherence of Plasmodium falciparum-infected erythrocytes containing sickle hemoglobin. Proc. Nat. Acad. Sci. 105: 991-996, 2008. [PubMed: 18192399] [Full Text: https://doi.org/10.1073/pnas.0711401105]

  233. Chotivanich, K., Udomsangpetch, R., Pattanapanyasat, K., Chierakul, W., Simpson, J., Looareesuwan, S., White, N. Hemoglobin E: a balanced polymorphism protective against high parasitemias and thus severe P falciparum malaria. Blood 100: 1172-1176, 2002. [PubMed: 12149194]

  234. Chow, E. Y., Haley, L. P., Krikler, S. H., Wadsworth, L. D. Hb Seattle [beta-70(E14)ala-to-asp]: a report of a second kindred in a Ukrainian family. Hemoglobin 18: 231-234, 1994. [PubMed: 7928380] [Full Text: https://doi.org/10.3109/03630269409043624]

  235. Christopoulou, G., Tserga, A., Patrinos, G. P., Papadakis, M. N. Molecular characterization and diagnosis of Hb Crete [beta-129(H7)ala-to-pro]. Hemoglobin 28: 339-342, 2004. [PubMed: 15658190] [Full Text: https://doi.org/10.1081/hem-200037796]

  236. Church, G. M., Gilbert, W. Genomic sequencing. Proc. Nat. Acad. Sci. 81: 1991-1995, 1984. [PubMed: 6326095] [Full Text: https://doi.org/10.1073/pnas.81.7.1991]

  237. Ciavatta, D. J., Ryan, T. M., Farmer, S. C., Townes, T. M. Mouse model of human beta-0-thalassemia: targeted deletion of the mouse beta(maj)- and beta(min)-globin genes in embryonic stem cells. Proc. Nat. Acad. Sci. 92: 9259-9263, 1995. [PubMed: 7568113] [Full Text: https://doi.org/10.1073/pnas.92.20.9259]

  238. Cin, S., Akar, N., Cavdar, A. O., Arcasoy, A., Dedeoglu, S., Webber, B., Lam, H., Huisman, T. H. J. Hb Summer Hill or beta52(D3)asp-to-his in a Turkish family from Cyprus. Hemoglobin 7: 467-470, 1983. [PubMed: 6629828] [Full Text: https://doi.org/10.3109/03630268309038416]

  239. Clegg, J. B., Naughton, M. A., Weatherall, D. J. An improved method for the characterization of human haemoglobin mutants: identification of alpha-2, beta-2 (95 glu), haemoglobin N (Baltimore). Nature 207: 945-947, 1965. [PubMed: 5886928] [Full Text: https://doi.org/10.1038/207945a0]

  240. Clegg, J. B., Naughton, M. A., Weatherall, D. J. Abnormal human haemoglobins. Separation and characterization of the alpha and beta chains by chromatography, and the determination of two new variants, Hb Chesapeake and Hb J(Bangkok). J. Molec. Biol. 19: 91-108, 1966. [PubMed: 5967288] [Full Text: https://doi.org/10.1016/s0022-2836(66)80052-9]

  241. Clegg, J. B., Weatherall, D. J., Boon, W. H., Mustafa, D. Two new haemoglobin variants involving proline substitutions. Nature 222: 379-380, 1969. [PubMed: 5782115] [Full Text: https://doi.org/10.1038/222379a0]

  242. Cobian, J. G., Magana, M.-T., Perea, F. J., Ibarra, B. Hb Colima (beta-49(CD8)ser-to-cys): a new hemoglobin variant. Hemoglobin 26: 393-395, 2002. [PubMed: 12484635] [Full Text: https://doi.org/10.1081/hem-120016377]

  243. Cohen-Solal, M., Blouquit, Y., Garel, M. C., Gaillard, L., Creyssel, R., Gibaud, A., Rosa, J. Haemoglobin Lyon (beta 17-18 lys-val 0): determination by sequenator analysis. Biochim. Biophys. Acta 351: 306-316, 1974. [PubMed: 4407311]

  244. Cohen-Solal, M., Lebeau, M., Rosa, J. 'In vitro' normal biosynthesis of an unstable ferri-hemoglobin: hemoglobin Saint Louis B10 (beta 28) leu-to-gln. Nouv. Rev. Franc. Hemat. 14: 621-626, 1974. [PubMed: 4281476]

  245. Colah, R., Wadia, M., Surve, R., Nadkarni, A., Phanasgaonkar, S., Gorakshakar, A., Mohanty, D., Prome, D., Wajcman, H. Hb D-Agri [beta-9(A6)ser-tyr;beta-121(GH4)glu-gln]: a new Indian hemoglobin variant with two amino acid substitutions in the same beta chain. Hemoglobin 25: 317-321, 2001. [PubMed: 11570725] [Full Text: https://doi.org/10.1081/hem-100105225]

  246. Cole-Strauss, A., Yoon, K., Xiang, Y., Byrne, B. C., Rice, M. C., Gryn, J., Holloman, W. K., Kmiec, E. B. Correction of the mutation responsible for sickle cell anemia by an RNA-DNA oligonucleotide. Science 273: 1386-1388, 1996. [PubMed: 8703073] [Full Text: https://doi.org/10.1126/science.273.5280.1386]

  247. Coleman, M. B., Adams, J. G., Smith, C. M., Steinberg, M. H. Modulation of Hb Koln disease by an additional mutation: Hb Medicine Lake. (Abstract) Blood 82 (suppl. 1): 222a, 1993.

  248. Coleman, M. B., Lu, Z.-H., Smith, C. M., II, Adams, J. G., III, Harrell, A., Plonczynski, M., Steinberg, M. H. Two missense mutations in the beta-globin gene can cause severe beta thalassemia: hemoglobin Medicine Lake (beta-32[B14]leu-to-glu; 98[FG5]val-to-met). J. Clin. Invest. 95: 503-509, 1995. [PubMed: 7860732] [Full Text: https://doi.org/10.1172/JCI117691]

  249. Coleman, M. B., Steinberg, M. H., Adams, J. G., III. Hemoglobin Terre Haute arginine beta-106: a posthumous correction to the original structure of hemoglobin Indianapolis. J. Biol. Chem. 266: 5798-5800, 1991. [PubMed: 2005117]

  250. Coleman, M. D., Adams, J. G., Steinberg, M. H. A possible somatic mutation of the human beta-globin gene. (Abstract) Blood 72 (suppl. 1): 58a, 1988.

  251. Collins, F. S., Cole, J. L., Lockwood, W. K., Iannuzzi, M. C. The deletion in both common types of hereditary persistence of fetal hemoglobin is approximately 105 kilobases. Blood 70: 1797-1803, 1987. [PubMed: 2445400]

  252. Como, P. F., Hocking, D., Trent, R. A., Wilkinson, T., Wylie, B. R., Bruce, D., Kronenberg, H. Hb Geelong (beta139 asn-to-asp) and Hb Stanmore (beta111 val-to-ala): two new unstable haemoglobins which illustrate the problem of distinguishing a haemoglobin with a thalassaemic phenotype from one inherited along with beta thalassaemia in either cis or trans. (Abstract) Proceedings of the Haematology Society, Australia, Perth, West Australia, October 1984.

  253. Como, P. F., Kennett, D., Wilkinson, T., Kronenberg, H. A new hemoglobin with high oxygen affinity--hemoglobin Bunbury: beta(94 (FG1) asp-to-asn). Hemoglobin 7: 413-421, 1983. [PubMed: 6629823] [Full Text: https://doi.org/10.3109/03630268309038410]

  254. Converse, J., Sharma, V., Reiss-Rosenberg, G., Ranney, H. M., Danish, E., Bowman, L. S., Harris, J. W. Some properties of hemoglobin Mobile (beta73 asp-to-val). Hemoglobin 9: 33-45, 1985. [PubMed: 3997539] [Full Text: https://doi.org/10.3109/03630268508996980]

  255. Corso, D., Cognata, B., Ciaccio, C., Piazza, T., Dibenedetto, S. P., Samperi, P., Russo Mancuso, G., Schiliro, G. Hb Agenogi (beta90(F6)glu-to-lys) and beta-0-thalassemia in a Sicilian family. Hemoglobin 14: 549-553, 1990. [PubMed: 2079434] [Full Text: https://doi.org/10.3109/03630269009005807]

  256. Costa, J.-M., Benachi, A., Gautier, E. New strategy for prenatal diagnosis of X-linked disorders. (Letter) New Eng. J. Med. 346: 1502 only, 2002. [PubMed: 12000828] [Full Text: https://doi.org/10.1056/NEJM200205093461918]

  257. Cotton, F., Hansen, V., Lin, C., Parma, J., Cochaux, P., Damis, E., Vertongen, F., Gulbis, B. Hb Ube-2 (alpha-68(E17)asn-to-asp) and Hb Hafnia (beta-116(G18)his-to-gln) observed during neonatal screening in Brussels. Hemoglobin 24: 65-69, 2000. [PubMed: 10722118] [Full Text: https://doi.org/10.3109/03630260009002276]

  258. Cotton, R. G. H., Rodrigues, N. R., Campbell, R. D. Reactivity of cytosine and thymine in single-base-pair mismatches with hydroxylamine and osmium tetroxide and its application to the study of mutations. Proc. Nat. Acad. Sci. 85: 4397-4401, 1988. [PubMed: 3260032] [Full Text: https://doi.org/10.1073/pnas.85.12.4397]

  259. Currat, M., Trabuchet, G., Rees, D., Perrin, P., Harding, R. M., Clegg, J. B., Langaney, A., Excoffier, L. Molecular analysis of the beta-globin gene cluster in the Niokholo Mandenka population reveals a recent origin of the beta-S Senegal mutation. Am. J. Hum. Genet. 70: 207-223, 2002. [PubMed: 11741197] [Full Text: https://doi.org/10.1086/338304]

  260. Curtin, P., Pirastu, M., Kan, Y. W., Gobert-Jones, J. A., Stephens, A. D., Lehmann, H. A distant gene deletion affects beta-globin gene function in an atypical gamma-delta-beta-thalassemia. J. Clin. Invest. 76: 1554-1558, 1985. [PubMed: 2997283] [Full Text: https://doi.org/10.1172/JCI112136]

  261. Curtin, P. T., Liu, D., Liu, W., Chang, J. C., Kan, Y. W. Human beta-globin gene expression in transgenic mice is enhanced by a distant DNase I hypersensitive site. Proc. Nat. Acad. Sci. 86: 7082-7086, 1989. [PubMed: 2780563] [Full Text: https://doi.org/10.1073/pnas.86.18.7082]

  262. Curuk, M. A., Howard, S. C., Kutlar, A., Huisman, T. H. J. A newly discovered beta-zero-thalassemia (IVS-II-850, G-to-A) mutation in a North European family. Hemoglobin 19: 207-211, 1995. [PubMed: 7558878] [Full Text: https://doi.org/10.3109/03630269509036942]

  263. Cyrklaff, M., Sanchez, C. P., Kilian, N., Bisseye, C., Simpore, J., Frischknecht, F., Lanzer, M. Hemoglobins S and C interfere with actin remodeling in Plasmodium falciparum-infected erythrocytes. Science 334: 1283-1286, 2011. [PubMed: 22075726] [Full Text: https://doi.org/10.1126/science.1213775]

  264. Dacie, J. V., Shinton, N. K., Gaffney, P. J., Jr., Carrell, R. W., Lehmann, H. Haemoglobin Hammersmith (beta 42 (CD 1) phe to ser). Nature 216: 663-665, 1967. [PubMed: 6082463] [Full Text: https://doi.org/10.1038/216663a0]

  265. Danish, E. H., Harris, J. W., Ahmed, F., Anderson, H. Hb Rothschild (beta 37 (C3) trp-to-arg): clinical studies. Hemoglobin 6: 51-55, 1982. [PubMed: 7068435] [Full Text: https://doi.org/10.3109/03630268208996933]

  266. Dash, S., Das, R. Late emergence of polycythemia in a case of Hb Chandigarh [beta-94(FG1)asp-to-gly]. Hemoglobin 28: 273-274, 2004. [PubMed: 15481898] [Full Text: https://doi.org/10.1081/hem-120040311]

  267. Dash, S., Wilson, J. B., Webber, B. B., Kutlar, A., Huisman, T. H. J. Hb Chandigarh or beta94(FG1)asp-to-gly observed in an Indian family. Hemoglobin 13: 749-752, 1989. [PubMed: 2634672] [Full Text: https://doi.org/10.3109/03630268908998849]

  268. De Angioletti, M., Di Girgenti, C., Messineo, R., Capra, M., Carestia, C. Hb A2-Monreale (delta-146 (HC3) his-to-arg), a novel delta chain variant detected in west Sicily. Hemoglobin 26: 1-5, 2002. [PubMed: 11939506] [Full Text: https://doi.org/10.1081/hem-120002934]

  269. De Angioletti, M., Maglione, G., Ferranti, P., de Bonis, C., Lacerra, G., Scarallo, A., Pagano, L., Fioretti, G., Cutolo, R., Malorni, A., Pucci, P., Carestia, C. Hb City of Hope [beta69(E13)gly-to-ser] in Italy: association of the gene with haplotype IX. Hemoglobin 16: 27-34, 1992. [PubMed: 1353069] [Full Text: https://doi.org/10.3109/03630269209005673]

  270. De Biasi, R., Spiteri, D., Caldora, M., Iodice, R., Pucci, P., Malorni, A., Ferranti, P., Marino, G. Identification by fast atom bombardment mass spectrometry of Hb Indianapolis (beta112 (G14) cys-to-arg) in a family from Naples, Italy. Hemoglobin 12: 323-336, 1988. [PubMed: 3170235] [Full Text: https://doi.org/10.3109/03630268808998033]

  271. de Castro, C. M., Devlin, B., Fleenor, D. E., Lee, M. E., Kaufman, R. E. A novel beta-globin mutation, beta-Durham-NC (beta-114-leu-pro), produces a dominant thalassemia-like phenotype. Blood 83: 1109-1116, 1994. [PubMed: 8111050]

  272. De Jong, W. W. W., Went, L. N., Bernini, L. F. Abnormal haemoglobin--chemical characterization of hemoglobin Leiden. Nature 220: 788-789, 1968. [PubMed: 5698750] [Full Text: https://doi.org/10.1038/220788a0]

  273. de Pablos, J. M., Kutlar, A., Wilson, J. B., Webber, B. B., Hu, H., Huisman, T. H. J. Hb D-Granada or beta22 (B4) glu-to-val. Hemoglobin 11: 563-565, 1987. [PubMed: 3446652] [Full Text: https://doi.org/10.3109/03630268709027872]

  274. de Weinstein, B. I., Plaseska-Karanfilska, D., Efremov, G. D. Hb Saint Etienne or Hb Istanbul (beta-92(F8)his-to-gln) found in an Argentinean family. Hemoglobin 24: 149-152, 2000. [PubMed: 10870887] [Full Text: https://doi.org/10.3109/03630260009003435]

  275. Deacon-Smith, R. A., Lee-Potter, J. P. An unstable haemoglobin, Hb Tacoma beta 30 (B12) arg-to-ser, detected at birth by the demonstration of red cell inclusions. J. Clin. Path. 31: 883-887, 1978. [PubMed: 711920] [Full Text: https://doi.org/10.1136/jcp.31.9.883]

  276. deCastro, C. M., Lee, M., Fleenor, D. E., Devlin, B., Kaufman, R. E. A novel beta-globin mutation, beta-Durham-N.C. [beta(114) leu-to-pro], detected by SSCP, produces a dominant thalassemia-like phenotype. (Abstract) Blood 80: 6a, 1992.

  277. Deidda, G., Novelletto, A., Hafez, M., Al-Tonbary, Y., Felicetti, L., Terrenato, L., Colombo, B. A new beta-thalassemia produced by a single nucleotide substitution in the conserved dinucleotide sequence of the IVS-I consensus acceptor site (AG-to-AA). Hemoglobin 14: 431-440, 1990. [PubMed: 2283297] [Full Text: https://doi.org/10.3109/03630269009032003]

  278. Deisseroth, A., Nienhuis, A. W., Lawrence, J., Giles, R. E., Turner, P., Ruddle, F. H. Chromosomal localization of the human beta globin gene to human chromosome 11 in somatic cell hybrids. Proc. Nat. Acad. Sci. 75: 1456-1460, 1978. [PubMed: 274732] [Full Text: https://doi.org/10.1073/pnas.75.3.1456]

  279. Delanoe, J., North, M. L., Arous, N., Bardakjian, J., Pflumio, F., Brunagel, M. L., Lacombe, C., Poyart, C., Galacteros, F., Rosa, J., Blouquit, Y. Hb Saverne: a new variant having an elongated beta chain. (Abstract) Blood 64: 56a, 1984. Note: Abstract: Hemoglobin 9: 108 only, 1985.

  280. Delanoe-Garin, J., Arous, N., Blouquit, Y., Hafsia, R., Bardakdjian, J., Lacombe, C., Rosa, J., Galacteros, F. Hemoglobin Kenitra beta69 (E13) gly-to-arg: a new beta variant of elevated expression associated with alpha-thalassemia, found in a Moroccan woman. Hemoglobin 9: 1-9, 1985. [PubMed: 3838975] [Full Text: https://doi.org/10.3109/03630268508996977]

  281. Delanoe-Garin, J., Rhoda, M. D., Craescu, C. T., Bardakjian, J., Blouquit, Y., Lacombe, C., Arous, N., Poyart, C., Ganeval, D., Girot, R., Riou, J., Galacteros, F. Hemoglobin J Iran beta77 (EF1) his-to-asp in a Russian-Armenian family. Hemoglobin 10: 365-378, 1986. [PubMed: 2943700] [Full Text: https://doi.org/10.3109/03630268608996868]

  282. Deutsch, S., Darbellay, R., Offord, R., Frutiger, A., Kister, J., Wajcman, H., Beris, P. Hb Iraq-Halabja beta-10(A7)ala-to-val(GCC-to-GTC): a new beta-chain silent variant in a family with multiple Hb disorders. Am. J. Hemat. 61: 187-193, 1999. [PubMed: 10398311] [Full Text: https://doi.org/10.1002/(sici)1096-8652(199907)61:3<187::aid-ajh5>3.0.co;2-7]

  283. Devaraj, R., Wilson, J. B., Huisman, T. H. J. Hb Regina or beta96(FG3)leu-to-val: a high oxygen affinity variant discovered by cation-exchange HPLC. Am. J. Hemat. 19: 195-200, 1985. [PubMed: 3839106] [Full Text: https://doi.org/10.1002/ajh.2830190212]

  284. Dherte, P., Lehmann, H., Vandepitte, J. Haemoglobin P in a family in the Belgian Congo. Nature 184: 1133-1135, 1959. [PubMed: 13816360] [Full Text: https://doi.org/10.1038/1841133a0]

  285. Di Iorio, E. E., Winterhalter, K. H., Wilson, K., Rosenmund, A., Marti, H. R. Swiss family with hemoglobin P Galveston (beta-117 his-to-arg) including 2 patients with Hb P-beta thalassemia. Blut 31: 61-68, 1975. [PubMed: 1164567] [Full Text: https://doi.org/10.1007/BF01633721]

  286. Di Marzo, R., Dowling, C. E., Wong, C., Maggio, A., Kazazian, H. H., Jr. The spectrum of beta-thalassemia mutations in Sicily. Brit. J. Haemat. 69: 393-397, 1988. [PubMed: 3408672] [Full Text: https://doi.org/10.1111/j.1365-2141.1988.tb02379.x]

  287. Dianzani, I., Ramus, S., Cotton, R. G. H., Camaschella, C. A spontaneous mutation causing unstable Hb Hammersmith: detection of the beta42 TTT-to-TCT change by CCM and direct sequencing. Brit. J. Haemat. 79: 127-129, 1991. [PubMed: 1911375] [Full Text: https://doi.org/10.1111/j.1365-2141.1991.tb08026.x]

  288. Diaz-Chico, J. C., Huang, H. J., Juricic, D., Efremov, G. D., Wadsworth, L. D., Huisman, T. H. J. Two new large deletions resulting in epsilon-gamma-delta-beta-thalassemia. Acta Haemat. 80: 79-84, 1988. [PubMed: 3138875] [Full Text: https://doi.org/10.1159/000205607]

  289. Dickerman, J. D., Holtzman, N. A., Zinkham, W. H. Hemoglobin Zurich. A third family presenting hemolytic reactions to sulfonamides. Am. J. Med. 55: 638-642, 1973. [PubMed: 4749206] [Full Text: https://doi.org/10.1016/0002-9343(73)90186-1]

  290. Dincol, G., Dincol, K., Erdem, S. Hb G-Coushatta or beta22 (B4) glu-to-ala in a Turkish male. Hemoglobin 13: 75-77, 1989. [PubMed: 2703366] [Full Text: https://doi.org/10.3109/03630268908998054]

  291. Ding, C., Chiu, R. W. K., Lau, T. K., Leung, T. N., Chan, L. C., Chan, A. Y. Y., Charoenkwan, P., Ng, I. S. L., Law, H., Ma, E. S. K., Xu, X., Wanapirak, C., Sanguansermsri, T., Liao, C., Ai, M. A. T. J., Chui, D. H. K., Cantor, C. R. MS analysis of single-nucleotide differences in circulating nucleic acids: application to noninvasive prenatal diagnosis. Proc. Nat. Acad. Sci. 101: 10762-10767, 2004. [PubMed: 15247415] [Full Text: https://doi.org/10.1073/pnas.0403962101]

  292. Divoky, V., Bisse, E., Wilson, J. B., Gu, L.-H., Wieland, H., Heinrichs, I., Prior, J. F., Huisman, T. H. J. Heterozygosity for the IVS-I-5 (G-to-C) mutation with a G-to-A change at codon 18 (val-to-met; Hb Baden) in cis and a T-to-G mutation at codon 126 (val-to-gly; Hb Dhonburi) in trans resulting in a thalassemia intermedia. Biochim. Biophys. Acta 1180: 173-179, 1992. [PubMed: 1463768] [Full Text: https://doi.org/10.1016/0925-4439(92)90065-u]

  293. Divoky, V., Svobodova, M., Indrak, K., Chrobak, L., Molchanova, T. P., Huisman, T. H. J. Hb Hradec Kralove (Hb HK) or beta-115(G17)ala-to-asp, a severely unstable hemoglobin variant resulting in a dominant beta-thalassemia trait in a Czech family. Hemoglobin 17: 319-328, 1993. [PubMed: 7693620] [Full Text: https://doi.org/10.3109/03630269308997485]

  294. Djoumessi, S., Rousseaux, J., Dautrevaux, M. Structural studies of a new hemoglobin: Hb J Lens, beta13 (A10) ala-to-asp. FEBS Lett. 136: 145-147, 1981. [PubMed: 7319057] [Full Text: https://doi.org/10.1016/0014-5793(81)81234-3]

  295. Dlott, D., Frauenfelder, H., Langer, P., Roder, H., Di Iorio, E. E. Nanosecond flash photolysis study of carbon monoxide binding to the beta chain of hemoglobin Zurich (beta63(E7) his-to-arg). Proc. Nat. Acad. Sci. 80: 6239-6243, 1983. [PubMed: 6578506] [Full Text: https://doi.org/10.1073/pnas.80.20.6239]

  296. Dobbs, N. B., Jr., Simmons, J. W., Wilson, J. B., Huisman, T. H. J. Hemoglobin Jenkins or hemoglobin-N Baltimore or beta glu 95. Biochim. Biophys. Acta 117: 492-494, 1966. [PubMed: 5961314] [Full Text: https://doi.org/10.1016/0304-4165(66)90106-1]

  297. Dobkin, C., Pergolizzi, R. G., Bahre, P., Bank, A. Abnormal splice in a mutant human beta-globin gene not at the site of a mutation. Proc. Nat. Acad. Sci. 80: 1184-1188, 1983. [PubMed: 6298782] [Full Text: https://doi.org/10.1073/pnas.80.5.1184]

  298. Driscoll, M. C., Baird, M., Bank, A., Rachmilewitz, E. A. A new polymorphism in the human beta-globin gene useful in antenatal diagnosis. J. Clin. Invest. 68: 915-919, 1981. [PubMed: 6270195] [Full Text: https://doi.org/10.1172/jci110346]

  299. Driscoll, M. C., Dobkin, C. S., Alter, B. P. Gamma-delta-beta-thalassemia due to a de novo mutation deleting the 5-prime beta-globin gene activation-region hypersensitive sites. Proc. Nat. Acad. Sci. 86: 7470-7474, 1989. [PubMed: 2798417] [Full Text: https://doi.org/10.1073/pnas.86.19.7470]

  300. Duwig, I., North, M. L., Barth, J. G., Rieffel, M., Nierengarten, P., Arous, N., Riou, J., Galacteros, F. Aspects hematologiques et anomalies structurales d'une nouvelle hemoglobine instable: l'Hb Sarrebourg beta(131) (H9) gln-to-arg. (Abstract) Nouv. Rev. Franc. Hemat. 29: 344, 1987.

  301. Dye, M. J., Proudfoot, N. J. Multiple transcript cleavage precedes polymerase release in transcription by RNA polymerase II. Cell 105: 669-681, 2001. [PubMed: 11389836] [Full Text: https://doi.org/10.1016/s0092-8674(01)00372-5]

  302. Economou, E. P., Antonarakis, S. E., Dowling, C. E., Ibarra, B., de la Nova, E., Kazazian, H. H., Jr. Molecular characterization of beta-thalassemia in Mexicans. (Abstract) Clin. Res. 38: 387A, 1990.

  303. Edgar, R. S. Conditional lethals. In: Cairns, J.; Stent, G. S.; Watson, J. D.: Phage and the Origins of Molecular Biology. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory (pub.) 1966. Pp. 166-170.

  304. Edington, G. M., Lehmann, H., Schneider, R. G. Characterization and genetics of haemoglobin G. Nature 175: 850-851, 1955. [PubMed: 14370233] [Full Text: https://doi.org/10.1038/175850a0]

  305. Edison, E. S., Shaji, R. V., Devi, S. G., Kumar, S. S., Srivastava, A., Chandy, M. Hb Showa-Yakushiji (beta-110(G12)leu-to-pro) in four unrelated patients from West Bengal. Hemoglobin 29: 19-25, 2005. [PubMed: 15768552]

  306. Edison, E. S., Shaji, R. V., Srivastava, A., Chandy, M. Hyperbilirubinemia in homozygous HbE disease is associated with the UGT1A1 gene polymorphism. Hemoglobin 29: 189-195, 2005. [PubMed: 16114182] [Full Text: https://doi.org/10.1081/hem-200066314]

  307. Efremov, G. D., Duma, H., Rudivic, R., Rolovic, Z., Wilson, J. B., Huisman, T. H. J. Hemoglobin Beograd or beta 121 glu-to-val (GH4). Biochim. Biophys. Acta 328: 81-83, 1973. [PubMed: 4761994] [Full Text: https://doi.org/10.1016/0005-2795(73)90332-2]

  308. Efremov, G. D., Huisman, T. H. J., Smith, L. L., Wilson, J. B., Kitchens, J. L., Wrightstone, R. N., Adams, H. R. Hemoglobin Richmond, a human hemoglobin which forms asymmetric hybrids with other hemoglobins. J. Biol. Chem. 244: 6105-6116, 1969. [PubMed: 4981790]

  309. Efremov, G. D., Huisman, T. H. J., Stanulovic, M., Zurovec, M., Duma, H., Wilson, J. B., Jeremic, V. Haemoglobin M Saskatoon and Haemoglobin M Hyde Park in two Yugoslavian families. Scand. J. Haemat. 13: 48-60, 1974. [PubMed: 4413625] [Full Text: https://doi.org/10.1111/j.1600-0609.1974.tb00234.x]

  310. Efremov, G. D., Jankovic, L., Juricic, D., Stojancov, A., Wilson, J. B., Webber, B. B., Kutlar, F., Kutlar, A., Hu, H., Huisman, T. H. J. Hb Bushwick [beta74(E18)gly-to-val] heterozygotes in a Yugoslavian family have 35 to 40% of the unstable variant. Hemoglobin 11: 557-562, 1987. [PubMed: 3446651]

  311. Efstratiadis, A., Posakony, J. W., Maniatis, T., Lawn, R. M., O'Connell, C., Spritz, R. A., DeRiel, J. K., Forget, B. G., Weissman, S. M., Slightom, J. L., Blechl, A. E., Smithies, O., Baralle, F. E., Shoulders, C. C., Proudfoot, N. J. The structure and evolution of the human beta-globin gene family. Cell 21: 653-668, 1980. [PubMed: 6985477] [Full Text: https://doi.org/10.1016/0092-8674(80)90429-8]

  312. Eigel, A., Schnee, J., Oehme, R., Horst, J. Mutation analysis of beta-thalassemia genes in a German family reveals a rare transversion in the first intron. Hum. Genet. 81: 371-372, 1989. [PubMed: 2703241] [Full Text: https://doi.org/10.1007/BF00283694]

  313. El-Hazmi, M. A. F., Jabbar, F. A., Al-Swailem, A. R., Warsy, A. S. Beta-globin gene polymorphism in Saudis--triple Hpa I fragments. Hum. Genet. 74: 313-315, 1986. [PubMed: 2877940] [Full Text: https://doi.org/10.1007/BF00282555]

  314. El-Hazmi, M. A. F., Lehmann, H. Hemoglobin Riyadh--beta 120 (GH3) lys-to-asn: a new variant found in association with alpha-thalassemia and iron deficiency. Hemoglobin 1: 59-74, 1977.

  315. Elder, G. E., Lappin, T. R. J., Horne, A. B., Fairbanks, V. F., Jones, R. T., Winter, P. C., Green, B. N., Hoyer, J. D., Reynolds, T. M., Shih, D. T.-B., McCormick, D. J., Kubik, K. S., Madden, B. J., Head, C. G., Harvey, D., Roberts, N. B. Hemoglobin Old Dominion/Burton-upon-Trent, beta-143 (H21) his-to-tyr, codon 143 CAC-to-TAC--a variant with altered oxygen affinity that compromises measurement of glycated hemoglobin in diabetes mellitus: structure, function, and DNA sequence. Mayo Clin. Proc. 73: 321-328, 1998. [PubMed: 9559035]

  316. Elion, J., Belkhodja, O., Wajcman, H., Labie, D. Two variants of hemoglobin D in the Algerian population: hemoglobin D Ouled Rabah beta-19 (BI) asn-to-lys and hemoglobin D Iran beta-22 (B4) glu-to-gln. Biochim. Biophys. Acta 310: 360-364, 1973. [PubMed: 4719147] [Full Text: https://doi.org/10.1016/0005-2795(73)90117-7]

  317. Elion, J., Wajcman, H., Belkhodja-Dunda, O., Lapoumeroulie, C., Labie, D., Messerschmitt, J., Staal, A. M., Desablens, B. Hemoglobin J Amiens, beta17 (A14) lys replaced by asn: coincidence of a functionally silent new abnormal hemoglobin and a polycythemia vera. Nouv. Rev. Franc. Hemat. 21: 347-352, 1979. [PubMed: 121938]

  318. Elwan, S., Baklouti, F., El-Kabsh, M., Abdelrahman, F., Delaunay, J. Hemoglobin Knossos (beta27 (B9) ala-to-ser) in Egypt. Hemoglobin 11: 139-143, 1987. [PubMed: 3114175] [Full Text: https://doi.org/10.3109/03630268709005788]

  319. Embury, S. H., Scharf, S. J., Saiki, R. K., Gholson, M. A., Golbus, M., Arnheim, N., Erlich, H. A. Rapid prenatal diagnosis of sickle cell anemia by a new method of DNA analysis. New Eng. J. Med. 316: 656-661, 1987. [PubMed: 3821796] [Full Text: https://doi.org/10.1056/NEJM198703123161103]

  320. Enoki, Y., Ohga, Y., Furukawa, K., Takaya, A., Sakata, S., Kohzuki, H., Shimizu, S., Tsujii, T. Hb Hope, beta136 (H14) gly-to-asp, in a diabetic Japanese female and its functional characterization. Hemoglobin 13: 17-32, 1989. [PubMed: 2703363] [Full Text: https://doi.org/10.3109/03630268908998050]

  321. Enver, T., Raich, N., Ebens, A. J., Papayannopoulou, T., Costantini, F., Stamatoyannopoulos, G. Developmental regulation of human fetal-to-adult globin gene switching in transgenic mice. Nature 344: 309-313, 1990. [PubMed: 2314472] [Full Text: https://doi.org/10.1038/344309a0]

  322. Epner, E., Reik, A., Cimbora, D., Telling, A., Bender, M. A., Fiering, S., Enver, T., Martin, D. I. K., Kennedy, M., Keller, G., Groudine, M. The beta-globin LCR is not necessary for an open chromatin structure of developmentally regulated transcription of the native mouse beta-globin locus. Molec. Cell. 2: 447-455, 1998. [PubMed: 9809066] [Full Text: https://doi.org/10.1016/s1097-2765(00)80144-6]

  323. Epstein, R. H., Bolle, A., Steinberg, C. M., Kellenberger, E., Boy de la Tour, E., Chevalley, R., Edgar, R. S., Susman, M., Denhardt, G. H., Lielausis, A. Physiological studies of conditional lethal mutants of bacteriophage T4D. Cold Spring Harbor Symp. Quant. Biol. 28: 375-394, 1963.

  324. Fabritius, H., Cabannes, R., Boissel, J. P., Wacjman, H., Labie, D. Hemoglobin Cocody (beta21(B3)asp-to-asn): hematologic aspects of heterozygosity and of Hb Cocody/beta(+) thalassemia. Hemoglobin 9: 193-196, 1985. [PubMed: 4030382] [Full Text: https://doi.org/10.3109/03630268508997003]

  325. Fabry, M. E., Kaul, D. K., Raventos, C., Baez, S., Rieder, R., Nagel, R. L. Some aspects of the pathophysiology of homozygous Hb CC erythrocytes. J. Clin. Invest. 67: 1284-1291, 1981. [PubMed: 7229029] [Full Text: https://doi.org/10.1172/jci110156]

  326. Fairbanks, V. F., Jones, R. T., Head, C., Vogel, S. R., Oliveros, R., Brimhall, B., Silverstein, M. N., Berzins, R. Two families with hemoglobin Sogn, beta-(A11)14 leu-to-arg, in Minnesota and Indiana: hematologic, functional, and biosynthetic features. Mayo Clin. Proc. 65: 793-798, 1990. [PubMed: 2366586] [Full Text: https://doi.org/10.1016/s0025-6196(12)62568-3]

  327. Fairbanks, V. F., Maldonado, J. E., Charache, S., Boyer, S. H. Familial erythrocytosis due to electrophoretically undetectable hemoglobin with impaired oxygen dissociation (hemoglobin Malmo, beta 97 gln). Mayo Clin. Proc. 46: 721-727, 1971. [PubMed: 5128393]

  328. Fairbanks, V. F., Oliveros, R., Brandabur, J. H., Willis, R. R., Fiester, R. F. Homozygous hemoglobin E mimics beta-thalassemia minor without anemia or hemolysis: hematologic, functional, and biosynthetic studies of first North American cases. Am. J. Hemat. 8: 109-121, 1980. [PubMed: 7395858] [Full Text: https://doi.org/10.1002/ajh.2830080112]

  329. Fairbanks, V. F., Opfell, R. W., Burgert, E. O., Jr. Three families with unstable hemoglobinopathies (Koln, Olmsted and Santa Ana) causing hemolytic anemia with inclusion bodies and pigmenturia. Am. J. Med. 46: 344-359, 1969. [PubMed: 5780360] [Full Text: https://doi.org/10.1016/0002-9343(69)90037-0]

  330. Fairhurst, R. M., Baruch, D. I., Brittain, N. J., Ostera, G. R., Wallach, J. S., Hoang, H. L., Hayton, K., Guindo, A., Makobongo, M. O., Schwartz, O. M., Tounkara, A., Doumbo, O. K., Diallo, D. A., Fujioka, H., Ho, M., Wellems, T. E. Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria. Nature 435: 1117-1121, 2005. [PubMed: 15973412] [Full Text: https://doi.org/10.1038/nature03631]

  331. Falcioni, G., Grelloni, F., de Sanctis, G., Pierani, P., Felici, L., Coppa, G. V. Enzymatic antioxidative defence of erythrocytes in an Italian family with Hb Volga or beta27(B9)ala-to-asp. (Letter) Clin. Chim. Acta 178: 345-348, 1988. [PubMed: 3240605] [Full Text: https://doi.org/10.1016/0009-8981(88)90243-4]

  332. Faustino, P., Miranda, A., do Ceu Silva, M., Alves, C., Picanco, I., Ferreira, C., Seixas, M. T., Pina, F., Romao, L. Hb Yaounde [beta-134(H12)val-to-ala] in association with Hb C [beta-6(A3)glu-to-lys] in a Caucasian Portuguese family. Hemoglobin 28: 229-235, 2004. [PubMed: 15481891] [Full Text: https://doi.org/10.1081/hem-120040259]

  333. Faustino, P., Osorio-Almeida, L., Barbot, J., Espirito-Santo, D., Goncalves, J., Romao, L., Martins, M. C., Marques, M. M., Lavinha, J. Novel promoter and splice junction defects add to the genetic, clinical or geographic heterogeneity of beta-thalassaemia in the Portuguese population. Hum. Genet. 89: 573-576, 1992. [PubMed: 1634236] [Full Text: https://doi.org/10.1007/BF00219188]

  334. Faustino, P., Osorio-Almeida, L., Romao, L., Barbot, J., Fernandes, B., Justica, B., Lavinha, J. Dominantly transmitted beta-thalassemia arising from the production of several aberrant mRNA species and one abnormal peptide. Blood 91: 685-690, 1998. [PubMed: 9427726]

  335. Fay, K. C., Brennan, S. O., Costello, J. M., Potter, H. C., Williamson, D. A., Trent, R. J., Ockelford, P. A., Boswell, D. R. Haemoglobin Manukau beta-67 [E11] val-to-gly: transfusion-dependent haemolytic anaemia ameliorated by coexisting alpha thalassaemia. Brit. J. Haemat. 85: 352-355, 1993. [PubMed: 8280608] [Full Text: https://doi.org/10.1111/j.1365-2141.1993.tb03178.x]

  336. Fedorov, A. N., Rasulov, E. M., Bocharova, T. N., Smirnova, E. A., Limborska, S. A. The T-to-A mutation at position -30 of the beta-globin gene found in a Karachai patient with beta-thalassemia intermedia. Hemoglobin 16: 521-523, 1992. [PubMed: 1487424] [Full Text: https://doi.org/10.3109/03630269208993121]

  337. Fei, Y. J., Stoming, T. A., Efremov, G. D., Battacharia, R., Gonzalez-Redondo, J. M., Altay, C., Gurgey, A., Huisman, T. H. J. Beta-thalassemia due to a T-to-A mutation within the ATA box. Biochem. Biophys. Res. Commun. 153: 741-747, 1988. [PubMed: 3382401] [Full Text: https://doi.org/10.1016/s0006-291x(88)81157-4]

  338. Fei, Y. J., Stoming, T. A., Kutlar, A., Huisman, T. H. J., Stamatoyannopoulos, G. One form of inclusion body beta-thalassemia is due to a GAA-to-TAA mutation at codon 121 of the beta chain. Blood 73: 1075-1077, 1989. [PubMed: 2563949]

  339. Felice, A., Abraham, E. C., Miller, A., Stallings, M., Huisman, T. H. J. Is the trimodality of Hb Leslie (beta 131 Gln-to-0) in heterozygotes the result of a variable number of active alpha-chain genes? Evidence for posttranslational control of hemoglobin synthesis. Am. J. Hemat. 5: 1-9, 1978. [PubMed: 747178] [Full Text: https://doi.org/10.1002/ajh.2830050102]

  340. Feliu-Torres, A., Eberle, S. E., Roldan, A., Gonzalez, S., Sciuccati, G. Hb Johnstown [beta-109(G11)val-to-leu]: a high oxygen affinity variant associated with beta-0-thalassemia. Hemoglobin 28: 335-338, 2004. [PubMed: 15658189] [Full Text: https://doi.org/10.1081/hem-200037799]

  341. Ferreira, A., Marguti, I., Bechmann, I., Jeney, V., Chora, A., Palha, N. R., Rebelo, S., Henri, A., Beuzard, Y., Soares, M. P. Sickle hemoglobin confers tolerance to Plasmodium infection. Cell 145: 398-409, 2011. [PubMed: 21529713] [Full Text: https://doi.org/10.1016/j.cell.2011.03.049]

  342. Filon, D., Faerman, M., Smith, P., Oppenheim, A. Sequence analysis reveals a beta-thalassemia mutation in the DNA of skeletal remains from the archaeological site of Akhziv, Israel. Nature Genet. 9: 365-368, 1995. [PubMed: 7795641] [Full Text: https://doi.org/10.1038/ng0495-365]

  343. Finney, R., Casey, R., Lehmann, H., Walker, W. Hb Newcastle: beta 92 (F8) his-to-pro. FEBS Lett. 60: 435-438, 1975. [PubMed: 1227988] [Full Text: https://doi.org/10.1016/0014-5793(75)80766-6]

  344. Fischel-Ghodsian, N., Hirsch, P. C., Bohlman, M. C. Rapid detection of the hemoglobin C mutation by allele-specific polymerase chain reaction. (Letter) Am. J. Hum. Genet. 47: 1023-1024, 1990. [PubMed: 2239966]

  345. Fisher, C., Hanslip, J., Green, B. N., Gupta, V., Old, J. M., Rees, D. C. Hb Watford (beta-1(NA1)val-to-gly): a new, clinically silent hemoglobin variant in linkage with a new neutral mutation (Cap+36(G-A)). Hemoglobin 24: 347-353, 2000. [PubMed: 11186267] [Full Text: https://doi.org/10.3109/03630260008993144]

  346. Flatz, G., Kinderlerer, J. L., Kilmartin, J. V., Lehmann, H. Haemoglobin Tak: a variant with additional residues at the end of the beta-chains. Lancet 297: 732-733, 1971. Note: Originally Volume I. [PubMed: 4101432] [Full Text: https://doi.org/10.1016/s0140-6736(71)91994-5]

  347. Flatz, G., Sanguansermsri, T., Sengchanh, S., Horst, D., Horst, J. The 'hot spot' of Hb E [beta-26(B8)glu-to-lys] in Southeast Asia: beta-globin anomalies in the Lao Theung population of Southern Laos. Hemoglobin 28: 197-204, 2004. [PubMed: 15481886] [Full Text: https://doi.org/10.1081/hem-120040334]

  348. Flavell, R. A., Kooter, J. M., De Boer, E. Analysis of the beta-delta-globin gene loci in normal and Hb Lepore DNA: direct determination of gene linkage and intergene distance. Cell 15: 25-41, 1978. [PubMed: 699045] [Full Text: https://doi.org/10.1016/0092-8674(78)90080-6]

  349. Flint, J., Harding, R. M., Clegg, J. B., Boyce, A. J. Why are some genetic diseases common? Distinguishing selection from other processes by molecular analysis of globin gene variants. Hum. Genet. 91: 91-117, 1993. [PubMed: 8462981] [Full Text: https://doi.org/10.1007/BF00222709]

  350. Forget, B. G. Nucleotide sequence of human beta globin messenger RNA. Hemoglobin 1: 879-881, 1977. [PubMed: 342458] [Full Text: https://doi.org/10.3109/03630267709003915]

  351. Forget, B. G. Molecular genetics of human hemoglobin synthesis. Ann. Intern. Med. 91: 605-616, 1979. [PubMed: 384860] [Full Text: https://doi.org/10.7326/0003-4819-91-4-605]

  352. Francina, A., Lacombe, C., Baklouti, F., Dorleac, E., Delaunay, J., Souillet, G., Rudigoz, R. C., Arous, N., Rosa, J., Galacteros, F. A new case of Hb Little Rock (beta143(H21)his-to-gln), a high affinity variant: study during pregnancy. Hemoglobin 11: 113-122, 1987. [PubMed: 3623972] [Full Text: https://doi.org/10.3109/03630268709005784]

  353. Frick, P. G., Hitzig, W. H., Betke, K. Hemoglobin Zurich. I. A new hemoglobin anomaly associated with acute hemolytic episodes with inclusion bodies after sulfonamide therapy. Blood 20: 261-271, 1962. [PubMed: 13895148]

  354. Frischknecht, H., Ventruto, M., Hess, D., Hunziker, P., Rosatelli, M. C., Cao, A., Breitenstein, U., Fehr, J., Tuchschmid, P. Hb Hinwil or beta-38(C4)thr-to-asn: a new beta-chain variant detected in a Swiss family. Hemoglobin 20: 31-40, 1996. [PubMed: 8745430] [Full Text: https://doi.org/10.3109/03630269609027908]

  355. Fritsch, E. F., Lawn, R. M., Maniatis, T. Characterisation of deletions which affect the expression of fetal globin genes in man. Nature 279: 598-603, 1979. [PubMed: 450109] [Full Text: https://doi.org/10.1038/279598a0]

  356. Fritsch, E. F., Lawn, R. M., Maniatis, T. Molecular cloning and characterization of the human beta-like globin gene cluster. Cell 19: 959-972, 1980. [PubMed: 6155216] [Full Text: https://doi.org/10.1016/0092-8674(80)90087-2]

  357. Fucharoen, S., Fucharoen, G., Fucharoen, P., Fukumaki, Y. A novel ochre mutation in the beta-thalassemia gene of a Thai: identification by direct cloning of the entire beta-globin gene amplified using polymerase chain reactions. J. Biol. Chem. 264: 7780-7783, 1989. [PubMed: 2542242]

  358. Fujisawa, K., Yamashiro, K., Hattori, Y., Ohba, Y., Kajita, T., Kageyama, S., Arita, J. Hb Higashitochigi (Hb HT) [beta24 (B6) or beta 25 (B7) glycine deleted]: a new unstable variant expressing cyanosis. Hemoglobin 17: 467-473, 1993. [PubMed: 8294206] [Full Text: https://doi.org/10.3109/03630269308997502]

  359. Gacon, G., Belkhodja, O., Wajcman, H., Labie, D., Najman, A. Structural and functional studies of Hb Rothschild (beta 37 (C3) trp-to-arg): a new variant of the alpha-1-beta-2 contact. FEBS Lett. 82: 243-246, 1977. [PubMed: 913596] [Full Text: https://doi.org/10.1016/0014-5793(77)80593-0]

  360. Gacon, G., Krishnamoorthy, R., Wajcman, H., Labie, D., Tapon, J., Cosson, A. Hemoglobin Djelfa beta 98 (FG5) val-to-ala: isolation and functional properties of the heme saturated form. Biochim. Biophys. Acta 490: 156-163, 1977. [PubMed: 13850] [Full Text: https://doi.org/10.1016/0005-2795(77)90115-5]

  361. Gacon, G., Wajcman, H., Labie, D. Structural and functional study of Hb Nancy beta145 (HC2) tyr-to-asp: a high oxygen affinity hemoglobin. FEBS Lett. 56: 39-42, 1975. [PubMed: 239863] [Full Text: https://doi.org/10.1016/0014-5793(75)80106-2]

  362. Galacteros, F., Delanoe-Garin, J., Monplaisir, N., Arous, N., Blouquit, Y., Mamalaki, A., Tulliez, M., Ouka, M., Goossens, M., Rosa, J. Two new cases of heterozygosity for hemoglobin Knossos alpha-2,beta-2 27 ala-to-ser detected in the French West Indies and Algeria. Hemoglobin 8: 215-228, 1984. [PubMed: 6469698] [Full Text: https://doi.org/10.3109/03630268408996970]

  363. Galanello, R., Perseu, L., Barella, S., Satta, S., Fais, A., Era, B., Corda, M. Hb Belfast [beta-15(A12)trp-to-arg]: definition of the clinical and hematological phenotype. Hemoglobin 28: 217-222, 2004. [PubMed: 15481889] [Full Text: https://doi.org/10.1081/hem-120040219]

  364. Gale, R. E., Blair, N. E., Huehns, E. R., Clegg, J. B. Hb A-like sickle haemoglobin: Hb S-Providence. Brit. J. Haemat. 70: 251-252, 1988. [PubMed: 3191036] [Full Text: https://doi.org/10.1111/j.1365-2141.1988.tb02472.x]

  365. Gallienne, A. E., Dreau, H. M., McCarthy, J., Timbs, A. T., Hampson, J. M., Schuh, A., Old, J. M., Henderson, S. J. Multiplex ligation-dependent probe amplification identification of 17 different beta-globin gene deletions (including four novel mutations) in the UK population. Hemoglobin 33: 406-416, 2009. [PubMed: 19958185] [Full Text: https://doi.org/10.3109/03630260903344564]

  366. Game, L., Bergounioux, J., Close, J. P., Marzouka, B. E., Thein, S. L. A novel deletion causing (episilon-gamma-delta-beta)O thalassemia in a Chilean family. Brit. J. Haemat. 123: 154-159, 2003. [PubMed: 14510959] [Full Text: https://doi.org/10.1046/j.1365-2141.2003.04564.x]

  367. Gammack, D. B., Huehns, E. R., Lehmann, H., Shooter, E. M. The abnormal polypeptide chains in a number of haemoglobin variants. Acta Genet. Statist. Med. 11: 1-16, 1961. [PubMed: 13703277] [Full Text: https://doi.org/10.1159/000151139]

  368. Garel, M. C., Blouquit, Y., Arous, N., Rosa, J. Hb Strasbourg beta 20 (B2) val-to-asp: a variant at the same locus as Hb Olympia beta 20 val-to-met. FEBS Lett. 72: 1-4, 1976. [PubMed: 1001451] [Full Text: https://doi.org/10.1016/0014-5793(76)80799-5]

  369. Garel, M. C., Blouquit, Y., Rosa, J. Hemoglobin Castilla (beta 32 (B14) leu-to-arg): a new unstable variant producing severe hemolytic disease. FEBS Lett. 58: 144-148, 1975. [PubMed: 1225574] [Full Text: https://doi.org/10.1016/0014-5793(75)80245-6]

  370. Garel, M. C., Hassan, W., Coquelet, M. T., Goossens, M., Rosa, J., Arous, N. Hemoglobin J(Cairo): beta 65(E9) lys-to-gln, a new hemoglobin variant discovered in an Egyptian family. Biochim. Biophys. Acta 420: 97-104, 1976. [PubMed: 1247583] [Full Text: https://doi.org/10.1016/0005-2795(76)90348-2]

  371. Garewal, G., Fearon, C. W., Warren, T. C., Marwaha, N., Marwaha, R. K., Mahadik, C., Kazazian, H. H., Jr. The molecular basis of beta thalassaemia in Punjabi and Maharashtran Indians includes a multilocus aetiology involving triplicated alpha-globin loci. Brit. J. Haemat. 86: 372-376, 1994. [PubMed: 8199027] [Full Text: https://doi.org/10.1111/j.1365-2141.1994.tb04742.x]

  372. Gaudry, C. L., Jr., Pitel, P. A., Jue, D. L., Hine, T. K., Johnson, M. H., Moo-Penn, W. F. Hb Jacksonville [beta54(D5)val-to-asp]: a new unstable variant found in a patient with hemolytic anemia. Hemoglobin 14: 653-659, 1990. [PubMed: 2101840]

  373. Geever, R. F., Wilson, L. B., Nallaseth, F. S., Milner, P. F., Bittner, M., Wilson, J. T. Direct identification of sickle cell anemia by blot hybridization. Proc. Nat. Acad. Sci. 78: 5081-5085, 1981. [PubMed: 6272289] [Full Text: https://doi.org/10.1073/pnas.78.8.5081]

  374. George, P. M., Myles, T., Williamson, D., Higuchi, R., Symmans, W. A., Brennan, S. O. A family with haemolytic anaemia and three beta-globins: the deletion in haemoglobin Atlanta-Coventry (beta75 leu-to-pro, 141 leu deleted) is not present at the nucleotide level. Brit. J. Haemat. 81: 93-98, 1992. [PubMed: 1520631] [Full Text: https://doi.org/10.1111/j.1365-2141.1992.tb08178.x]

  375. Gerald, P. S., Efron, M. L. Chemical studies of several varieties of Hb M. Proc. Nat. Acad. Sci. 47: 1758-1767, 1961. [PubMed: 13897827] [Full Text: https://doi.org/10.1073/pnas.47.11.1758]

  376. Gerald, P. S., George, P. Second spectroscopically abnormal methemoglobin associated with hereditary cyanosis. Science 129: 393-394, 1959. [PubMed: 13634986] [Full Text: https://doi.org/10.1126/science.129.3346.393]

  377. Gerhard, D. S., Jones, C., Morse, H. G., Handelin, B., Weeks, V., Housman, D. Analysis of human chromosome 11 by somatic cell genetics: reexamination of derivatives of human-hamster cell line J1. Somat. Cell Molec. Genet. 13: 293-304, 1987. [PubMed: 3331828] [Full Text: https://doi.org/10.1007/BF01534923]

  378. Gerhard, D. S., Kidd, K. K., Kidd, J. R., Egeland, J. A., Housman, D. E. Identification of a recent recombination event within the human beta-globin gene cluster. Proc. Nat. Acad. Sci. 81: 7875-7879, 1984. [PubMed: 6096866] [Full Text: https://doi.org/10.1073/pnas.81.24.7875]

  379. Geva, A., Clark, J. J., Zhang, Y., Popowicz, A., Manning, J. M., Neufeld, E. J. Hemoglobin Jamaica Plain--a sickling hemoglobin with reduced oxygen affinity. New Eng. J. Med. 351: 1532-1538, 2004. [PubMed: 15470216] [Full Text: https://doi.org/10.1056/NEJMoa040771]

  380. Giambona, A., Vinciguerra, M., Cassara, F., Li Muli, R., Leto, F., Passarello, C., Wajcman, H., Maggio, A. Hb Marineo [beta-70 (E14) ala-to-val]: a silent hemoglobin variant with a mutation within the heme pocket. Hemoglobin 30: 139-148, 2006. [PubMed: 16798637] [Full Text: https://doi.org/10.1080/03630260600642005]

  381. Giardina, B., Brunori, M., Antonini, E., Tentori, L. Properties of hemoglobin G Ferrara (beta 57(E1) asn-to-lys). Biochim. Biophys. Acta 534: 1-6, 1978. [PubMed: 26414] [Full Text: https://doi.org/10.1016/0005-2795(78)90469-5]

  382. Gibb, E. A. Increased subunit association of a new superstable variant hemoglobin Motown. Clin. Res. 29: 795A, 1981. Note: Sponsored by D. L. Rucknagel.

  383. Gilbert, A. T., Fleming, P. J., Hertzberg, M. S. A second case of Hb Bologna-St. Orsola (beta-146(HC3)his-to-tyr) in an unrelated family of Anglo-Celtic origin. Hemoglobin 24: 139-142, 2000. [PubMed: 10870885] [Full Text: https://doi.org/10.3109/03630260009003433]

  384. Gilbert, A. T., Fleming, P. J., Hertzberg, M. S. Two unrelated cases of Hb Old Dominion/Burton-upon-Trent (beta-143(H21)his-to-tyr): a rare variant causing spuriously elevated Hb A(1C) values. Hemoglobin 24: 163-164, 2000. [PubMed: 10870890] [Full Text: https://doi.org/10.3109/03630260009003438]

  385. Gilbert, A. T., Fleming, P. J., Sumner, D. R., Hughes, W. G., Holland, R. A. B., Tibben, E. A. Hemoglobin Windsor or beta-11 (A8) val-to-asp: a new unstable beta-chain hemoglobin variant producing a hemolytic anemia. Hemoglobin 13: 437-453, 1989. [PubMed: 2599880] [Full Text: https://doi.org/10.3109/03630268908998083]

  386. Gilbert, A. T., Fleming, P. J., Sumner, D. R., Hughes, W. G., Ip, F., Kwan, Y. L., Holland, R. A. B. Hemoglobin Randwick or beta15 (A12) trp-to-gly: a new unstable beta-chain hemoglobin variant. Hemoglobin 12: 149-161, 1988. [PubMed: 3384707] [Full Text: https://doi.org/10.3109/03630268808998021]

  387. Giordano, P. C., Harteveld, C. L., Bernini, L. F., Doorduijn, J. K., Geenen, A. A., Kok, P. J. M., Versteegh, F. G. A. Haplotype analysis of two new, independent cases of Hb Osu-Christiansborg. Hemoglobin 23: 193-195, 1999. [PubMed: 10335988] [Full Text: https://doi.org/10.3109/03630269908996165]

  388. Girodon, E., Ghanem, N., Vidaud, M., Riou, J., Martin, J., Galacteros, F., Goossens, M. Rapid molecular characterization of mutations leading to unstable hemoglobin beta-chain variants. Ann. Hemat. 65: 188-192, 1992. [PubMed: 1420507] [Full Text: https://doi.org/10.1007/BF01703113]

  389. Glynn, K. P., Penner, J. A., Smith, J. R. Familial erythrocytosis: a description of three families, one with hemoglobin Ypsilanti. Ann. Intern. Med. 69: 769-776, 1968. [PubMed: 5687529] [Full Text: https://doi.org/10.7326/0003-4819-69-4-769]

  390. Goldsmith, M. E., Humphries, R. K., Ley, T., Cline, A., Kantor, J. A., Nienhuis, A. W. Silent substitution in beta-plus-thalassemia gene activating a cryptic splice site in beta-globin RNA coding sequence. Proc. Nat. Acad. Sci. 80: 2318-2322, 1983. [PubMed: 6572978] [Full Text: https://doi.org/10.1073/pnas.80.8.2318]

  391. Gonzalez-Redondo, J. M., Kattamis, C., Huisman, T. H. J. Characterization of three types of beta-0-thalassemia resulting from a partial deletion of the beta-globin gene. Hemoglobin 13: 377-392, 1989. [PubMed: 2753736] [Full Text: https://doi.org/10.3109/03630268909003400]

  392. Gonzalez-Redondo, J. M., Sicilia, A., Murga, M. J., Kutlar, A., Wilson, J. B., Huisman, T. H. J. Hb E-Saskatoon or beta22(B4)glu-to-lys in a Spanish family. Hemoglobin 11: 35-38, 1987. [PubMed: 3108201] [Full Text: https://doi.org/10.3109/03630268709036579]

  393. Gonzalez-Redondo, J. M., Stoming, T. A., Kutlar, F., Kutlar, A., Hu, H., Wilson, J. B., Huisman, T. H. J. Hb Monroe or beta30 (B12) arg-to-thr, a variant associated with beta-thalassemia due to a G-to-C substitution adjacent to the donor splice site of the first intron. Hemoglobin 13: 67-74, 1989. [PubMed: 2539344] [Full Text: https://doi.org/10.3109/03630268908998053]

  394. Gonzalez-Redondo, J. M., Stoming, T. A., Lanclos, K. D., Gu, Y. C., Kutlar, A., Kutlar, F., Nakatsuji, T., Deng, B., Han, I. S., McKie, V. C., Huisman, T. H. J. Clinical and genetic heterogeneity in black patients with homozygous beta-thalassemia from the southeastern United States. Blood 72: 1007-1014, 1988. [PubMed: 2458145]

  395. Goossens, M., Garel, M. C., Auvinet, J., Basset, P., Ferreira Gomes, P., Rosa, J. Hemoglobin C Ziguinchor beta 6 glu-to-val and beta 58 pro-to-arg: the second sickling variant with amino acid substitutions in 2 residues of the beta polypeptide chain. FEBS Lett. 58: 149-154, 1975. [PubMed: 1225575] [Full Text: https://doi.org/10.1016/0014-5793(75)80246-8]

  396. Gordon-Smith, E. C., Dacie, J. V., Blecher, T. E., French, E. A., Wiltshirre, B. G., Lehmann, H. Haemoglobin Nottingham, beta FG 5(98) val-to-gly: a new unstable haemoglobin producing severe haemolysis. Proc. Roy. Soc. Med. 66: 507-508, 1973. [PubMed: 4781799]

  397. Gottlieb, A. J., Robinson, E. A., Itano, H. A. Primary structure of Hopkins-1 haemoglobin-A. Nature 214: 189-190, 1967. [PubMed: 6034218] [Full Text: https://doi.org/10.1038/214189a0]

  398. Gouagna, L. C., Bancone, G., Yao, F., Yameogo, B., Dabire, K. R., Costantini, C., Simpore, J., Ouedraogo, J. B., Modiano, D. Genetic variation in human HBB is associated with Plasmodium falciparum transmission. Nature Genet. 42: 328-331, 2010. [PubMed: 20305663] [Full Text: https://doi.org/10.1038/ng.554]

  399. Greaves, D. R., Fraser, P., Vidal, M. A., Hedges, M. J., Ropers, D., Luzzatto, L., Grosveld, F. A transgenic mouse model of sickle cell disorder. Nature 343: 183-185, 1990. [PubMed: 2296310] [Full Text: https://doi.org/10.1038/343183a0]

  400. Greer, J., Perutz, M. F. Three dimensional structure of haemoglobin Rainier. Nature 230: 261-264, 1971.

  401. Grignoli, C. R. E., Wenning, M. R. S. C., Sonati, M. F., Kimura, E. M., Arruda, V. R., Saad, S. T. O., Costa, F. F. Hb Rio Clara [beta-34(B16)val to met]: a novel electrophoretically silent variant found in association with Hb Hasharon [alpha-47(CE5)asp to his] and alpha-thalassemia-2 (-alpha-3.7). Hemoglobin 23: 177-182, 1999. [PubMed: 10335985] [Full Text: https://doi.org/10.3109/03630269908996162]

  402. Groff, P., Kalmes, G., Golinska, B., Miyazaki, A., Riou, J., Carte, N., Prome, D., Kister, J., Galacteros, F., Wajcman, H. Hb Ernz (beta-123(H1)thr-to-asn) and Hb Renert (beta-133(H11)val-to-ala): two new neutral variants revealed by reversed phase high performance liquid chromatography analysis. Hemoglobin 24: 287-297, 2000. [PubMed: 11186258] [Full Text: https://doi.org/10.3109/03630260008993135]

  403. Grosveld, F., van Assendelft, G. B., Greaves, D. R., Kollias, G. Position-independent, high-level expression of the human beta-globin gene in transgenic mice. Cell 51: 975-985, 1987. [PubMed: 3690667] [Full Text: https://doi.org/10.1016/0092-8674(87)90584-8]

  404. Gu, L.-H., Leonova, J. Y., Huisman, T. H. J. Hb S-Hb Lufkin disease in a black male patient. Hemoglobin 19: 291-294, 1995. [PubMed: 8537234] [Full Text: https://doi.org/10.3109/03630269509005817]

  405. Gurgey, A., Altay, C., Gu, L.-H., Leonova, J. Y., Delibalta, A., Oner, C., Huisman, T. H. J. Hb Hakkari or alpha(2)beta(2)31(B13)leu-to-arg, a severely unstable hemoglobin variant associated with numerous intra-erythroblastic inclusions and erythroid hyperplasia of the bone marrow. Hemoglobin 19: 165-172, 1995. [PubMed: 7558872] [Full Text: https://doi.org/10.3109/03630269509036936]

  406. Gurgey, A., Sipahioglu, M., Aksoy, M. Compound heterozygosity for Hb E-Saskatoon or beta22(B4)glu-to-lys and beta-thalassemia type IVS-I-6 (T-to-C). Hemoglobin 14: 449-451, 1990. [PubMed: 2283299] [Full Text: https://doi.org/10.3109/03630269009032006]

  407. Gurney, H., Baig, I., Gordon, S., Phadke, K., Kearsley, H., Fleming, P., Wyatt, K., Hughes, W. A second Australian family with hemoglobin North Shore (beta134 val-to-glu). Pathology 19: 62-63, 1987. [PubMed: 3588028] [Full Text: https://doi.org/10.3109/00313028709065138]

  408. Gusella, J., Varsanyi-Breiner, A., Kao, F.-T., Jones, C., Puck, T. T., Keys, C., Orkin, S., Housman, D. Precise localization of human beta-globin gene complex on chromosome 11. Proc. Nat. Acad. Sci. 76: 5239-5243, 1979. [PubMed: 291941] [Full Text: https://doi.org/10.1073/pnas.76.10.5239]

  409. Haigh, L. S., Anderson, W. F., Francke, U. Regional mapping of the beta-globin gene on 11p. (Abstract) Cytogenet. Cell Genet. 25: 162-163, 1979.

  410. Hall, G. W., Sampietro, M., Barnetson, R., Fitzgerald, J., McCann, S., Thein, S. Meiotic recombination in an Irish family with beta-thalassaemia. Hum. Genet. 92: 28-32, 1993. [PubMed: 8103502] [Full Text: https://doi.org/10.1007/BF00216141]

  411. Hamaguchi, K., Kusuda, Y., Yoshimichi, G., Hanada, R., Harano, K., Harano, T., Sakata, T. Hb I-High Wycombe (beta-59(E3)lys-to-glu): the first instance in Japan. Hemoglobin 24: 153-156, 2000. [PubMed: 10870888] [Full Text: https://doi.org/10.3109/03630260009003436]

  412. Hamilton, H. B., Iuchi, I., Miyaji, T., Shibata, S. Hemoglobin Hiroshima (beta 143 histidine to aspartic acid): a newly identified fast moving beta chain variant associated with increased oxygen affinity and compensatory erythremia. J. Clin. Invest. 48: 525-535, 1969. [PubMed: 5773089] [Full Text: https://doi.org/10.1172/JCI106010]

  413. Han, J. Y., Wee, J. H., Kim, J. M., Kim, J. Y., Kim, I. H., Rodgers, G. P. A new observation of Hb Yamagata with a different nucleotide substitution: beta-132 AAA-to-AAT. Hemoglobin 20: 165-168, 1996. [PubMed: 8811322] [Full Text: https://doi.org/10.3109/03630269609027924]

  414. Hanada, M., Ohta, Y., Imamura, T., Fejimura, T., Kawasaki, K., Kosaka, K., Yamaoka, K., Seita, M. Studies of abnormal hemoglobins in western Japan. (Abstract) Jpn. J. Hum. Genet. 9: 253-254, 1964.

  415. Harano, K., Harano, T., Koide, G., Akimaru, S. Hb Nakano [beta-8(lys-to-met)]: a new beta chain variant found in a Japanese woman. Hemoglobin 19: 397-401, 1995. [PubMed: 8718698] [Full Text: https://doi.org/10.3109/03630269509005831]

  416. Harano, K., Harano, T., Shibata, S., Ueda, S., Mori, H., Seki, M. Hb Okazaki (beta93(F8)cys-to-arg): a new hemoglobin variant with increased oxygen affinity and instability. FEBS Lett. 173: 45-47, 1984. Note: Abstract: Hemoglobin 9: 109 only, 1985. [PubMed: 6745435] [Full Text: https://doi.org/10.1016/0014-5793(84)81014-5]

  417. Harano, K., Harano, T., Ueda, S., Mori, H., Shibata, S., Takeda, I., Tsunematsu, T. Hb Tacoma (beta30[B12] arg-to-ser), a slightly unstable hemoglobin variant found in Japan. Hemoglobin 9: 635-639, 1985. [PubMed: 3937827] [Full Text: https://doi.org/10.3109/03630268508997047]

  418. Harano, K., Harano, T., Ueda, S., Ohkushi, T., Imai, K. A new hemoglobin variant, Hb Mito (beta144 (HC1) lys-to-glu) with increased oxygen affinity. FEBS Lett. 192: 75-78, 1985. [PubMed: 2865170] [Full Text: https://doi.org/10.1016/0014-5793(85)80046-6]

  419. Harano, T., Harano, K., Katsuki, T. Hb Yaizu (beta79(EF3)asp--asn): a new beta chain variant found in a Japanese female. Hemoglobin 19: 21-25, 1995. [PubMed: 7615399] [Full Text: https://doi.org/10.3109/03630269509069726]

  420. Harano, T., Harano, K., Kushida, Y., Imai, K., Nishinakamura, R., Matsunaga, T. Hb Kodaira [beta-146(HC3)his-to-gln]: a new beta chain variant with an amino acid substitution at the C-terminus. Hemoglobin 16: 85-91, 1992. [PubMed: 1634367] [Full Text: https://doi.org/10.3109/03630269209005681]

  421. Harano, T., Harano, K., Kushida, Y., Ueda, S., Kawakami, H. Hb J-Amiens [beta17(A14)lys-to-asn] found in a Japanese. Hemoglobin 14: 445-448, 1990. [PubMed: 2101004] [Full Text: https://doi.org/10.3109/03630269009032005]

  422. Harano, T., Harano, K., Kushida, Y., Ueda, S., Yoshii, A., Nishinarita, M. Hb Isehara (or Hb Redondo) [beta-92(F8)his-to-asn]: an unstable variant with proximal histidine substitution at the heme contact. Hemoglobin 15: 279-290, 1991. [PubMed: 1787097] [Full Text: https://doi.org/10.3109/03630269109027880]

  423. Harano, T., Harano, K., Kushida, Y., Ueda, S. Structural analysis of abnormal hemoglobin by the polymerase chain reaction. Jpn. J. Clin. Path. 38: 1067-1072, 1990.

  424. Harano, T., Harano, K., Kushida, Y., Ueda, S. A new abnormal variant, Hb Yahata or beta-112(G14)cys-to-tyr, found in a Japanese: structural confirmation by DNA sequencing of the beta-globin gene. Hemoglobin 15: 109-113, 1991. [PubMed: 1917530] [Full Text: https://doi.org/10.3109/03630269109072490]

  425. Harano, T., Harano, K., Shibata, S., Ueda, S., Mori, H., Arimasa, N. Hemoglobin Okayama (beta 2 (NA2) his replaced by gln): a new 'silent' hemoglobin variant with substituted amino acid residue at the 2,3-diphosphoglycerate binding site. FEBS Lett. 156: 20-22, 1983. [PubMed: 6852251] [Full Text: https://doi.org/10.1016/0014-5793(83)80239-7]

  426. Harano, T., Harano, K., Ueda, S., Imai, K., Marubashi, S. Hb Yamagata (beta132(H10)lys-to-asn): a new abnormal hemoglobin in a Japanese family. Hemoglobin 14: 207-211, 1990. [PubMed: 2272843] [Full Text: https://doi.org/10.3109/03630269009046962]

  427. Harano, T., Harano, K., Ueda, S., Imai, K., Ohkuma, A., Koya, Y., Takahashi, H. Hb Fukuoka (beta2(NA2)his-to-tyr): a new mutation at the 2,3-diphosphoglycerate binding site. Hemoglobin 14: 199-205, 1990. [PubMed: 2272842] [Full Text: https://doi.org/10.3109/03630269009046961]

  428. Harano, T., Harano, K., Ueda, S., Imai, N., Kitazumi, T. A new electrophoretically-silent hemoglobin variant: hemoglobin Kofu or beta84 (EF8) thr-to-ile. Hemoglobin 10: 417-420, 1986. [PubMed: 3744871] [Full Text: https://doi.org/10.3109/03630268608996871]

  429. Harano, T., Harano, K., Ueda, S., Nakaya, K. Hb D Los Angeles (beta121 glu-to-gln) in Japan. Hemoglobin 11: 177-180, 1987. [PubMed: 2887538] [Full Text: https://doi.org/10.3109/03630268709005795]

  430. Harano, T., Harano, K., Ueda, S., Nomura, Y., Nanjo, K., Miyamura, T. Beta-zero-thalassemia due to a nonsense mutation (beta-90 GAG-to-TAG). (Abstract) Acta Haemat. Jpn. 52: 410, 1989.

  431. Harano, T., Harano, K., Ueda, S., Shibata, S., Imai, K., Nakai, T. Hb Hope (beta136 (H14) gly-to-asp) in a Japanese family. Hemoglobin 7: 263-265, 1983. [PubMed: 6874374] [Full Text: https://doi.org/10.3109/03630268309048655]

  432. Harano, T., Harano, K., Ueda, S., Shibata, S., Imai, K., Seki, M. Hemoglobin Machida (beta6 (A3) glu-to-gln), a new abnormal hemoglobin discovered in a Japanese family: structure, function and biosynthesis. Hemoglobin 6: 531-535, 1982. [PubMed: 6129204] [Full Text: https://doi.org/10.3109/03630268209083766]

  433. Harano, T., Harano, K., Ueda, S., Shibata, S., Imai, K. Hemoglobin Ankara (beta10 (A7) ala-to-asp): properties and biosynthesis. Hemoglobin 5: 737-741, 1981. [PubMed: 7338476]

  434. Harano, T., Harano, K., Ueda, S., Shibata, S., Iuchi, I., Mizushima, J., Matsumoto, T., Harada, H. Hemoglobin Yusa (beta21(B3) asp-to-tyr), a new abnormal hemoglobin found in Japan. Hemoglobin 5: 121-131, 1981. [PubMed: 7216815] [Full Text: https://doi.org/10.3109/03630268108996918]

  435. Hardison, R. C., Chui, D. H. K., Giardine, B., Riemer, C., Patrinos, G. P., Anagnou, N., Miller, W., Wajcman, H. HbVar: a relational database of human hemoglobin variants and thalassemia mutations at the globin gene server. Hum. Mutat. 19: 225-233, 2002. [PubMed: 11857738] [Full Text: https://doi.org/10.1002/humu.10044]

  436. Harkness, D. R., Yu, C. K., Goldberg, M., Bradley, T. B. Novel studies on a 'silent' high affinity mutant hemoglobin (San Diego, beta 109 val-to-met). Hemoglobin 5: 33-46, 1981. [PubMed: 7204093] [Full Text: https://doi.org/10.3109/03630268108996909]

  437. Harteveld, C. L., Groeneveld, J. H. M., van Dam, B., Van Delft, P., Akkerman, N., Arkesteijn, S., Giordano, P. C. Hb Zoeterwoude (beta-23(B5)val-to-ala): a new beta-globin variant found in association with erythrocytosis. Hemoglobin 29: 11-17, 2005. [PubMed: 15768551]

  438. Harteveld, C. L., Osborne, C. S., Peters, M., van der Werf, S., Plug, R., Fraser, P., Giordano, P. C. Novel 112 kb (epsilon-G-gamma-A-gamma) delta-beta-thalassaemia deletion in a Dutch family. Brit. J. Haemat. 122: 855-858, 2003. [PubMed: 12930401] [Full Text: https://doi.org/10.1046/j.1365-2141.2003.04505.x]

  439. Harteveld, C. L., Thelen, M. H. M., Rutten, J. J. A., Leuverman, J., Akkermans, N., van Delft, P., Arkesteijn, S., Giordano, P. C. Hb Geldrop St. Anna (beta-94(FG1)asp-to-tyr): a new hemoglobin variant observed in a diabetic patient. Hemoglobin 29: 107-112, 2005. [PubMed: 15921162]

  440. Harteveld, C., Plug, R. J., Van Delft, P., Van Helden, W. C. H., Giordano, P. C. Hb 't Lange Land [beta-136(H14)gly-arg]: A new hemoglobin variant described in a Dutch patient of Chinese origin. Hemoglobin 25: 331-336, 2001. [PubMed: 11570727] [Full Text: https://doi.org/10.1081/hem-100105227]

  441. Harthoorn-Lasthuizen, E. J., Nabben, F. A. E., Kazanetz, E. G., Gu, L.-H., Molchanova, T. P., Huisman, T. H. J. Hb Mizuho or alpha(2)beta(2)68(E12)leu-to-pro in a young Dutch boy. Hemoglobin 19: 203-206, 1995. [PubMed: 7558877] [Full Text: https://doi.org/10.3109/03630269509036941]

  442. Hassan, W., Basset, P., Oudart, J. L., Goossens, M., Rosa, J. Properties of the double substituted hemoglobin C Ziguinchor (beta 6 glu-to-val 58 pro-to-arg). Hemoglobin 1: 487-501, 1977. [PubMed: 893143] [Full Text: https://doi.org/10.3109/03630267709027866]

  443. Hatton, C. S. R., Wilkie, A. O. M., Drysdale, H. C., Wood, W. G., Vickers, M. A., Sharpe, J., Ayyub, H., Pretorius, I. M., Buckle, V. J., Higgs, D. R. Alpha-thalassemia caused by a large (62 kb) deletion upstream of the human alpha-globin gene cluster. Blood 76: 221-227, 1990. [PubMed: 2364173]

  444. Hattori, Y., Okayama, N., Ohba, Y., Yamashiro, Y., Yamamoto, K., Yamamoto, K., Koyama, S., Sawada, U. A new beta-thalassemia allele, codon 26 (GAG-to-GTAG), found in a Japanese. Hemoglobin 22: 79-82, 1998. [PubMed: 9494052] [Full Text: https://doi.org/10.3109/03630269809071521]

  445. Hattori, Y., Yamamoto, K., Yamashiro, Y., Ohba, Y., Miyamura, S., Yamamoto, K., Matsuno, Y., Morishita, M., Miyaji, T., Era, T. Three beta-thalassemia mutations in the Japanese: IVS-II-1 (G-to-A), IVS-II-848 (C-to-G), and codon 90 (GAG-to-TAG). Hemoglobin 16: 93-97, 1992. [PubMed: 1634368] [Full Text: https://doi.org/10.3109/03630269209005682]

  446. Hattori, Y., Yamane, A., Yamashiro, Y., Matsuno, Y., Yamamoto, K., Yamamoto, K., Ohba, Y., Miyaji, T. Characterization of beta-thalassemia mutations among the Japanese. Hemoglobin 13: 657-670, 1989. [PubMed: 2634667] [Full Text: https://doi.org/10.3109/03630268908998843]

  447. Hayashi, A., Stamatoyannopoulos, G., Yoshida, A., Adamson, J. Haemoglobin Rainier: beta 145 (HC2) tyrosine to cysteine and haemoglobin Bethesda: beta 145 (HC2) tyrosine to histidine. Nature N. B. 230: 264-267, 1971. [PubMed: 5282843] [Full Text: https://doi.org/10.1038/newbio230264a0]

  448. Hayashi, A., Suzuki, T., Imai, K., Morimoto, H., Watari, H. Properties of hemoglobin M, Milwaukee-1 variant and its unique characteristic. Biochim. Biophys. Acta 194: 6-15, 1969. [PubMed: 4311041] [Full Text: https://doi.org/10.1016/0005-2795(69)90173-1]

  449. Hebbel, R. P., Eaton, J. W., Kronenberg, R. S., Zajani, E. D., Moore, L. G., Berger, E. M. Human llamas: adaptation to altitude in subjects with high hemoglobin oxygen affinity. J. Clin. Invest. 62: 593-600, 1978. [PubMed: 29054] [Full Text: https://doi.org/10.1172/JCI109165]

  450. Hebbel, R. P., Kronenberg, R. S., Eaton, J. W. Hypoxic ventilatory response in subjects with normal and high oxygen affinity hemoglobins. J. Clin. Invest. 60: 1211-1215, 1977. [PubMed: 908760] [Full Text: https://doi.org/10.1172/JCI108874]

  451. Heck, W., Wolf, H. Angeborener Herzfehler mit Cyanose durch pathologischen Blutfarbstoff (Hb-M). Ann. Paediat. 190: 135-146, 1958. [PubMed: 13509426]

  452. Hedlund, B., Paine, S., Smith, C. M., II, Raines, J., Morrison, W. T., Adams, J. G., III. Hemoglobin Minneapolis-Laos (beta118 (GH1) phe-to-tyr): a new hemoglobin variant with normal functional properties. Hemoglobin 8: 75-78, 1984. [PubMed: 6547119] [Full Text: https://doi.org/10.3109/03630268408996962]

  453. Hedrick, P. Estimation of relative fitnesses from relative risk data and the predicted future of haemoglobin alleles S and C. J. Evol. Biol. 17: 221-224, 2004. [PubMed: 15000665] [Full Text: https://doi.org/10.1046/j.1420-9101.2003.00635.x]

  454. Heller, P., Coleman, R. D., Yakulis, V. Hemoglobin M (Hyde Park): a new variant of abnormal methemoglobin in a Negro. (Abstract) J. Clin. Invest. 45: 1021, 1966.

  455. Heller, P., Yakulis, V. J., Rosenzweig, A. I., Abildgaard, C. F., Rucknagel, D. L. Mild homozygous beta-thalassemia: further evidence for the heterogeneity of beta-thalassemia genes. Ann. Intern. Med. 64: 52-61, 1966. [PubMed: 5900783] [Full Text: https://doi.org/10.7326/0003-4819-64-1-52]

  456. Heller, P. Hemoglobin M (Chicago) and M (Kankakee). In: Lehmann, H.; Betke, K.: Haemoglobin-Colloquium. Stuttgart: Georg Thieme Verlag (pub.) 1962. Pp. 47-49.

  457. Henthorn, J. S., Wajcman, H., Prome, D., Riou, J., Kister, J., Baudin-Creuza, V., Davies, S. C., Galacteros, F. Hb Harrow (beta-118(GH1)phe-to-cys): a new neutral hemoglobin variant. Hemoglobin 23: 273-279, 1999. [PubMed: 10490141] [Full Text: https://doi.org/10.3109/03630269909005709]

  458. Herrick, J. B. Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia. Arch. Intern. Med. 6: 517-521, 1910.

  459. Heusterspreute, M., Derclaye, I., Gala, J.-L., Van Geet, C., Ferrant, A., Malchaire, Y., Thonnard, J., Vaerman, J.-L., Philippe, M. Beta-thalassaemia in indigenous Belgian families: identification of a novel mutation. Hum. Genet. 98: 77-79, 1996. [PubMed: 8682512] [Full Text: https://doi.org/10.1007/s004390050163]

  460. Hidaka, K., Iuchi, I., Miyake, K., Nakahara, H., Iwakawa, G. Hb Fukuyama (beta77 (IF1) his-to-tyr): a new abnormal hemoglobin discovered in a Japanese. Hemoglobin 12: 391-394, 1988. [PubMed: 3170240] [Full Text: https://doi.org/10.3109/03630268808998038]

  461. Hill, R. L., Schwartz, H. C. A chemical abnormality in haemoglobin G. Nature 184: 641-642, 1959.

  462. Hill, R. L., Swenson, R. T., Schwartz, H. C. Characterization of a chemical abnormality in hemoglobin G. J. Biol. Chem. 235: 3182-3187, 1960. [PubMed: 13714317]

  463. Hirano, M., Ohba, Y., Imai, K., Ino, T., Morishita, Y., Matsui, T., Shimizu, S., Sumi, H., Yamamoto, K., Miyaji, T. Hb Toyoake: beta 142 (H20) ala-to-pro: a new unstable hemoglobin with high oxygen affinity. Blood 57: 697-704, 1981. [PubMed: 7470620]

  464. Hobolth, N. Haemoglobin M Arhus: I. Clinical family study. Acta Paediat. Scand. 54: 357-362, 1965.

  465. Hojas-Bernal, R., McNab-Martin, P., Fairbanks, V. F., Holmes, M. W., Hoyer, J. D., McCormick, D. J., Kubik, K. S. Hb Chile [beta-28(B10)leu to met]: an unstable hemoglobin associated with chronic methemoglobinemia and sulfonamide or methylene blue-induced hemolytic anemia. Hemoglobin 23: 125-134, 1999. [PubMed: 10335980] [Full Text: https://doi.org/10.3109/03630269908996157]

  466. Hollender, A., Lorkin, P. A., Lehmann, H., Svensson, B. New unstable haemoglobin Boras: beta 88 (F4) leucine-arginine. Nature 222: 953-955, 1969. [PubMed: 5789325] [Full Text: https://doi.org/10.1038/222953a0]

  467. Honig, G. R., Green, D., Shamsuddin, M., Vida, L. N., Mason, R. G., Gnarra, D. J., Maurer, H. S. Hemoglobin Abraham Lincoln, beta 32 (beta 14) leucine to proline: an unstable variant producing severe hemolytic disease. J. Clin. Invest. 52: 1746-1755, 1973. [PubMed: 4352462] [Full Text: https://doi.org/10.1172/JCI107356]

  468. Honig, G. R., Mason, R. G., Shamsuddin, M., Vida, L. N., Rao, K. R. P., Patel, A. R. Two new sickle cell syndromes: Hb S, Hb Camden, and alpha-thalassemia and Hb S in combination with Hb Tacoma. Blood 55: 655-660, 1980. [PubMed: 7357091]

  469. Honig, G. R., Seeler, R. A., Shamsuddin, M., Vida, L. N., Mompoint, M., Valcourt, E. Hemoglobin Korle Bu in a Mexican family. Hemoglobin 7: 185-189, 1983. [PubMed: 6671904] [Full Text: https://doi.org/10.3109/03630268309048646]

  470. Honig, G. R., Shamsuddin, M., Mason, R. G., Vida, L. N. Hemoglobin Lincoln Park: a beta-delta fusion (anti-Lepore) variant with an amino acid deletion in the delta chain-derived segment. Proc. Nat. Acad. Sci. 75: 1475-1479, 1978. [PubMed: 274735] [Full Text: https://doi.org/10.1073/pnas.75.3.1475]

  471. Honig, G. R., Vida, L. N., Latorraca, R., Divgi, A. B. Hb South Milwaukee (beta105 (G7) leu-to-phe): a newly-identified hemoglobin variant with high oxygen affinity. Am. J. Hemat. 34: 199-203, 1990. [PubMed: 2363414] [Full Text: https://doi.org/10.1002/ajh.2830340308]

  472. Honig, G. R., Vida, L. N., Rosenblum, B. B., Perutz, M. F., Fermi, G. Hemoglobin Warsaw (phe-beta-42(CD1)-to-val), an unstable variant with decreased oxygen affinity: characterization of its synthesis, functional properties, and structure. J. Biol. Chem. 265: 126-132, 1990. [PubMed: 2294098]

  473. Hopmeier, P., Binder, C., Gadner, H., Fischer, M. A case of the unstable Hb Genova (beta28 leu-to-pro) in an Arab child associated with severe haemolytic anaemia and growth retardation. Acta Haemat. 83: 39-41, 1990. [PubMed: 2105568] [Full Text: https://doi.org/10.1159/000205161]

  474. Horlein, H., Weber, G. Ueber chronische familiaere Methaemoglobinaemia und eine neue Modifikation des methaemoglobins. Dtsch. Med. Wschr. 73: 476-478, 1948. [PubMed: 18105244] [Full Text: https://doi.org/10.1055/s-0028-1118186]

  475. Horst, J., Oehme, R., Epplen, J. T., Kohne, E. Haemoglobin Freiburg: direct detection by synthetic oligonucleotide probes. Hum. Genet. 79: 172-174, 1988. [PubMed: 3391614] [Full Text: https://doi.org/10.1007/BF00280559]

  476. Horst, J., Oehme, R., Kleihauer, E., Kohne, E. DNA restriction mapping identifies the chromosome carrying the mutant Hb Presbyterian beta-globin gene. Hum. Genet. 64: 263-266, 1983. [PubMed: 6309649] [Full Text: https://doi.org/10.1007/BF00279406]

  477. Horst, J., Oehme, R., Kohne, E. Hemoglobin Koln: direct analysis of the gene mutation by synthetic DNA probes. Blood 68: 1175-1177, 1986. [PubMed: 3768534]

  478. Horst, J., Schafer, R., Kleihauer, E., Kohne, E. Analysis of the Hb M Milwaukee mutation at the DNA level. Brit. J. Haemat. 54: 643-648, 1983. [PubMed: 6307336] [Full Text: https://doi.org/10.1111/j.1365-2141.1983.tb02144.x]

  479. Housman, D., Gusella, J., Kao, F. T., Jones, C., Breiner, A., Keys, C., Orkin, S., Puck, T. T. Regional mapping of the human structural gene for hemoglobin beta on chromosome 11 using restriction endonuclease mapping and a regional clone panel. (Abstract) Cytogenet. Cell Genet. 25: 166, 1979.

  480. Housman, D. Personal Communication. Cambridge, Mass. 6/1979.

  481. Hoyer, J. D., Weinhold, J., Mailhot, E., Alter, D., McCormick, D. J., Snow, K., Kubik, K. S., Holmes, M. W., Fairbanks, V. F. Three new hemoglobin variants with abnormal oxygen affinity: Hb Saratoga Springs [alpha-40(C5)lys-to-asn (alpha-1)], Hb Santa Clara [beta-97(FG4)his-to-asn], and Hb Sparta [beta-103(G5)phe-to-val]. Hemoglobin 27: 235-241, 2003. [PubMed: 14649314] [Full Text: https://doi.org/10.1081/hem-120026048]

  482. Hoyer, J. D., Wick, M. J., Thibodeau, S. N., Kechteiger, K. S., Cook, J. D., Fairbanks, V. F. Hb Silver Springs [beta-131(H9)gln-to-his], a new hemoglobin variant found in six African-Americans. Hemoglobin 22: 37-44, 1998. [PubMed: 9494046] [Full Text: https://doi.org/10.3109/03630269809071515]

  483. Hoyer, J. D., Wick, M. J., Thibodeau, S. N., Viker, K. A., Conner, R., Fairbanks, V. F. Hb Tak confirmed by DNA analysis: not expressed as thalassemia in a Hb Tak/Hb E compound heterozygote. Hemoglobin 22: 45-52, 1998. [PubMed: 9494047] [Full Text: https://doi.org/10.3109/03630269809071516]

  484. Huang, S., Wong, C., Antonarakis, S. E., Ro-Lien, T., Lo, W. H. Y., Kazazian, H. H., Jr. The same 'TATA' box beta-thalassemia mutation in Chinese and U.S. blacks: another example of independent origins of mutation. Hum. Genet. 74: 162-164, 1986. [PubMed: 3021607] [Full Text: https://doi.org/10.1007/BF00282081]

  485. Huang, S., Zhou, X., Zhu, H., Ren, Z., Zeng, Y. Detection of beta-thalassemia mutations in the Chinese using amplified DNA from dried blood specimens. Hum. Genet. 84: 129-131, 1990. [PubMed: 2298448] [Full Text: https://doi.org/10.1007/BF00208926]

  486. Hubbard, M., Winton, E. F., Lindeman, J. G., Dessauer, P. L., Wilson, J. B., Wrightstone, R. N., Huisman, T. H. J. Hemoglobin Atlanta (beta 75 leu-to-pro): an unstable variant found in several members of a Caucasian family. Biochim. Biophys. Acta 386: 538-541, 1975. [PubMed: 1138885] [Full Text: https://doi.org/10.1016/0005-2795(75)90297-4]

  487. Huehns, E. R., Hecht, F., Yoshida, A., Stamatoyannopoulos, G., Hartman, J., Motulsky, A. G. Hemoglobin-Seattle (beta 76 glu): an unstable hemoglobin causing chronic hemolytic anemia. Blood 36: 209-218, 1970. [PubMed: 5427455]

  488. Huisman, T. H. J. (ed.). The beta- and delta-thalassemia repository. Hemoglobin 16: 237-258, 1992. [PubMed: 1517101] [Full Text: https://doi.org/10.3109/03630269208998865]

  489. Huisman, T. H. J., Brown, A. K., Efremov, G. D., Wilson, J. B., Reynolds, C. A., Uy, R., Smith, L. L. Hemoglobin Savannah (beta 6 (24) beta-glycine to valine): an unstable variant causing anemia with inclusion bodies. J. Clin. Invest. 50: 650-659, 1971. [PubMed: 5545125] [Full Text: https://doi.org/10.1172/JCI106535]

  490. Huisman, T. H. J., Carver, M.-F. H., Efremov, G. P. A Syllabus of Human Hemoglobin Variants (1996). Augusta, Ga.: The Sickle Cell Anemia Foundation 1996.

  491. Huisman, T. H. J., Horton, B., Bridges, M. T., Betke, K., Hitzig, W. H. A new abnormal human hemoglobin: hemoglobin-Zurich. Clin. Chim. Acta 6: 347-355, 1960.

  492. Huisman, T. H. J., Sydenstricker, V. P. Haematology: difference in gross structure of two electrophoretically identical 'minor' hemoglobin components. Nature 193: 489-491, 1962. [PubMed: 14449876] [Full Text: https://doi.org/10.1038/193489a0]

  493. Huisman, T. H. J., Wilson, J. B., Kutlar, A., Yang, K.-G., Chen, S.-S., Webber, B. B., Altay, C., Martinez, A. V. Hb J-Antakya or beta65 (E9) lys-to-met in a Turkish family and Hb Complutense or beta127 (H5) gln-to-glu in a Spanish family; correction of a previously published identification. Biochim. Biophys. Acta 871: 229-231, 1986. [PubMed: 3707969] [Full Text: https://doi.org/10.1016/0167-4838(86)90178-0]

  494. Huisman, T. H. J. Beta-thalassemia repository. Hemoglobin 14: 661-675, 1990. [PubMed: 2101841]

  495. Hull, D., Winter, P. C., McHale, C. M., Lappin, T. R. J., Mayne, E. E. Familial hemolytic anemia due to Hb Sabine (beta-91(F7)leu-to-pro) identified by polymerase chain reaction. Hemoglobin 22: 263-266, 1998. [PubMed: 9629500] [Full Text: https://doi.org/10.3109/03630269809113139]

  496. Hunt, J. A., Ingram, V. M. A terminal peptide sequence of human haemoglobin? Nature 184: 640-641, 1959.

  497. Hunt, J. A., Ingram, V. M. Abnormal human haemoglobins. VI. The chemical difference between hemoglobin A and E. Biochim. Biophys. Acta 49: 520-536, 1961. [PubMed: 13716853] [Full Text: https://doi.org/10.1016/0006-3002(61)90249-9]

  498. Husquinet, H., Parent, M. T., Schoos-Barbette, S., Dodinval-Versie, J., Lambotte, C., Galacteros, F. Hemoglobin D-Los Angeles (beta 121 (GH4) glu-to-gln) in the province of Liege, Belgium. Hemoglobin 10: 587-592, 1986. [PubMed: 3557993] [Full Text: https://doi.org/10.3109/03630268609036563]

  499. Hutchison, H. E., Pinkerton, P. H., Waters, P., Douglas, A. S., Lehmann, H., Beale, D. Hereditary Heinz-body anaemia, thrombocytopenia, and haemoglobinopathy (Hb Koln) in a Glasgow family. Brit. Med. J. 2: 1099-1103, 1964. [PubMed: 14198723] [Full Text: https://doi.org/10.1136/bmj.2.5417.1099]

  500. Hutt, P. J., Pisciotta, A. V., Fairbanks, V. F., Thibodeau, S. N., Green, M. M. DNA sequence analysis proves Hb M-Milwaukee-2 is due to beta-globin gene codon 92 (CAC-to-TAC), the presumed mutation of Hb M-Hyde Park and Hb M-Akita. Hemoglobin 22: 1-10, 1998. [PubMed: 9494043] [Full Text: https://doi.org/10.3109/03630269809071512]

  501. Hyde, R. D., Hall, M. D., Wiltshire, B. G., Lehmann, H. Haemoglobin Southampton, beta 106 (G8) leu to pro: an unstable variant producing severe haemolysis. Lancet 300: 1170-1172, 1972. Note: Originally Volume II. [PubMed: 4117593] [Full Text: https://doi.org/10.1016/s0140-6736(72)92594-9]

  502. Idelson, L. I., Didkowsky, N. A., Casey, R., Lorkin, P. A., Lehmann, H. New unstable haemoglobin (Hb Moscva, beta 24 (B6) gly-to-asp) found in the U.S.S.R. Nature 249: 768-770, 1974. [PubMed: 4525423] [Full Text: https://doi.org/10.1038/249768a0]

  503. Idelson, L. I., Didkowsky, N. A., Casey, R., Lorkin, P. A., Lehmann, H. Structure and function of haemoglobin Tacoma (beta 30 arg-to-ser) found in a second family. Acta Haemat. 52: 303-311, 1974. [PubMed: 4217534] [Full Text: https://doi.org/10.1159/000208255]

  504. Igarashi, Y., Matsuzaki, S., Kanou, N., Inami, S., Nakamura, T., Kasai, K., Fushitani, K. The first case of Hb E-Saskatoon [alpha(2)-beta(2)22(B4)glu-to-lys] in a Japanese male in Asia. Hemoglobin 19: 403-406, 1995. [PubMed: 8718699] [Full Text: https://doi.org/10.3109/03630269509005832]

  505. Ikkala, E., Koskela, J., Pikkarainen, P., Rahiala, I.-L., El-Hazmi, M. A. F., Nagai, K., Lang, A., Helmann, H. Hb Helsinki: a variant with a high oxygen affinity and a substitution at a 2,3-DPG binding site (beta 82 (EF6) lys-to-met). Acta Haemat. 56: 257-275, 1976. [PubMed: 826083] [Full Text: https://doi.org/10.1159/000207947]

  506. Imai, K., Morimoto, H., Kotani, M., Shibata, S., Miyaji, T., Mastutomo, K. Studies on the function of abnormal hemoglobins. II. Oxygen equilibrium of abnormal hemoglobins: Shimonoseki, Ube II, Hikari, Gifu and Agenogi. Biochim. Biophys. Acta 200: 197-202, 1970. [PubMed: 5416123] [Full Text: https://doi.org/10.1016/0005-2795(70)90164-9]

  507. Imai, K., Yoshioka, Y., Tyuma, I., Hirano, M. Functional abnormalities of hemoglobin Toyoake (142 (H20)beta, ala-to-pro). Biochim. Biophys. Acta 668: 1-15, 1981. [PubMed: 7236701] [Full Text: https://doi.org/10.1016/0005-2795(81)90143-4]

  508. Imamura, T., Fujita, S., Ohta, Y., Hanada, M., Yanase, T. Hemoglobin Yoshizuka (G10(108) beta asparagine to aspartic acid): a new variant with a reduced oxygen affinity from a Japanese family. J. Clin. Invest. 48: 2341-2348, 1969. [PubMed: 5355345] [Full Text: https://doi.org/10.1172/JCI106200]

  509. Imamura, T., Riggs, A. Identification of hemoglobin Oak Ridge with hemoglobin D Punjab (Los Angeles). Biochem. Genet. 7: 127-130, 1972. [PubMed: 5050915] [Full Text: https://doi.org/10.1007/BF00486083]

  510. Indrak, K., Wiedermann, B. F., Batek, F., Wilson, J. B., Webber, B. B., Kutlar, A., Huisman, T. H. J. Hb Olomouc or beta86 (F2) ala-to-asp, a new high oxygen affinity variant. Hemoglobin 11: 151-155, 1987. [PubMed: 3623975] [Full Text: https://doi.org/10.3109/03630268709005790]

  511. Ingle, J., Adewoye, A., Dewan, R., Okoli, M., Rollins, L., Eung, S. H., Luo, H., Chui, D. H. K., Steinberg, M. H. Hb Hope [beta-136(H14)gly-to-asp (GGT-to-GAT)]: interactions with Hb S [beta-6(A3)glu-to-val (GAG-to-GTG)], other variant hemoglobins and thalassemia. Hemoglobin 28: 277-285, 2004. [PubMed: 15658184] [Full Text: https://doi.org/10.1081/hem-200037801]

  512. Ingram, V. M. A specific chemical difference between the globins of normal human and sickle-cell anemia haemoglobin. Nature 178: 792-794, 1956. [PubMed: 13369537] [Full Text: https://doi.org/10.1038/178792a0]

  513. Ingram, V. M. Gene mutations in human haemoglobin: the chemical difference between normal and sickle cell haemoglobin. Nature 180: 326-328, 1957. [PubMed: 13464827] [Full Text: https://doi.org/10.1038/180326a0]

  514. Ingram, V. M. Abnormal human haemoglobin. III. The chemical difference between normal and sickle cell haemoglobins. Biochim. Biophys. Acta 36: 402-411, 1959. [PubMed: 13852872] [Full Text: https://doi.org/10.1016/0006-3002(59)90183-0]

  515. Itano, H. A., Neel, J. V. A new inherited abnormality of human hemoglobin. Proc. Nat. Acad. Sci. 36: 613-617, 1950. [PubMed: 14808148] [Full Text: https://doi.org/10.1073/pnas.36.11.613]

  516. Iuchi, I., Hidaka, K., Harano, T., Ueda, S., Shibata, S., Shimasaki, S., Mizushima, J., Kubo, N., Miyake, T., Uchida, T. Hemoglobin Takamatsu (beta120 (GH 3) lys-to-gln): a new abnormal hemoglobin detected in three unrelated families in the Takamatsu area of Shikoku. Hemoglobin 4: 165-176, 1980. [PubMed: 7390862] [Full Text: https://doi.org/10.3109/03630268009042383]

  517. Iuchi, I., Shimasaki, S., Hidaka, K., Ueda, S., Harano, T., Shibata, S., Mizushima, J., Ohnishi, Y. Hemoglobin J Bangkok (beta56(D7)gly-to-asp): a hemoglobin variant discovered by the hemoglobinopathy survey in Takamatsu district. Hemoglobin 5: 199-204, 1981. [PubMed: 7216820] [Full Text: https://doi.org/10.3109/03630268108996926]

  518. Iuchi, I., Ueda, S., Hidaka, K., Shibata, S. Hemoglobin Hoshida (beta 43 (CD-2) glu-to-gln), a new hemoglobin variant discovered in Japan. Hemoglobin 2: 235-247, 1978. [PubMed: 701082] [Full Text: https://doi.org/10.3109/03630267809007069]

  519. Ivaldi, G., David, O., Baffico, M., Leone, D., Baldi, M., Parodi, M. I., Scime-Degani, V., Piga, A., Scagni, P., Rabino-Massa, E., Ricco, G. Hb Trento: an elongated C-terminal beta chain due to a new frameshift mutation [beta-144 (-A)]. Hemoglobin 27: 15-25, 2003. [PubMed: 12603089] [Full Text: https://doi.org/10.1081/hem-120018432]

  520. Ivaldi, G., David, O., Paradossi, V., Baffico, M., Degani, V. S., Leone, D., Baldi, M., Parodi, M. I., Bernardi, P., Ricco, G. Hb Bologna-St. Orsola (beta-146(HC3)his-to-tyr): a new high oxygen affinity variant with halved Bohr effect and highly reduced reactivity towards 2,3-diphosphoglycerate. Hemoglobin 23: 353-359, 1999. [PubMed: 10569724] [Full Text: https://doi.org/10.3109/03630269909090751]

  521. Ivaldi, G., Scime-Degani, V., David, O., Baffico, M., Baldi, M., Leone, D., Mazzocco, M., Leone, L., Piga, A., Furlan, E., Ricco, G. A new fast-moving variant causing erythrocytosis and mild hemolysis: Hb Gambara (beta-82(EF6)lys-to-glu). Hemoglobin 21: 345-361, 1997. [PubMed: 9255613] [Full Text: https://doi.org/10.3109/03630269709000667]

  522. Jackson, J. M., Way, B. J., Woodliff, H. J. A west Australian family with a haemolytic disorder associated with haemoglobin Koln. Brit. J. Haemat. 13: 474-481, 1967. [PubMed: 6029950] [Full Text: https://doi.org/10.1111/j.1365-2141.1967.tb00757.x]

  523. Jackson, J. M., Yates, A., Huehns, E. R. Haemoglobin Perth: beta 32 (B14) leu-to-pro, an unstable haemoglobin causing haemolysis. Brit. J. Haemat. 25: 607-610, 1973. [PubMed: 4127713] [Full Text: https://doi.org/10.1111/j.1365-2141.1973.tb01773.x]

  524. Jacquette, A., Le Roux, G., Lacombe, C., Goossens, M., Pissard, S. Compound heterozygosity for two new mutations in the beta-globin gene [codon 9 (+TA) and polyadenylation site (AATAAA-AAAAAA)] leads to thalassemia intermedia in a Tunisian patient. Hemoglobin 28: 243-248, 2004. [PubMed: 15481893] [Full Text: https://doi.org/10.1081/hem-120040304]

  525. Jankovic, L., Dimovski, A. J., Sukarova, E., Juricic, D., Efremov, G. D. A new mutation in the beta-globin gene (IVS II-850 G-C) found in a Yugoslavian beta-thalassemia heterozygote. Haematologica 77: 119-121, 1992. [PubMed: 1398296]

  526. Jankovic, L., Efremov, G. D., Josifovska, O., Juricic, D., Stoming, T. A., Kutlar, A., Huisman, T. H. J. An initiation codon mutation as a cause of a beta-thalassemia. Hemoglobin 14: 169-176, 1990. [PubMed: 2272840] [Full Text: https://doi.org/10.3109/03630269009046958]

  527. Jankovic, L., Efremov, G. D., Petkov, G., Kattamis, C., George, E., Yang, K.-G., Stoming, T. A., Huisman, T. H. J. Three novel mutations leading to beta-thalassemia. (Abstract) 31st Annual Meeting of the American Society of Hematology, Atlanta, December 1989.

  528. Jeffreys, A. J., Flavell, R. A. The rabbit beta-globin gene contains a large insert in the coding sequence. Cell 12: 1097-1108, 1977. [PubMed: 597859] [Full Text: https://doi.org/10.1016/0092-8674(77)90172-6]

  529. Jen, P. C., Chen, L. C., Chen, P. F., Wong, Y., Chen, L. F., Guo, Y. Y., Chang, F. Q., Chow, Y. C., Chiu, Y. Hemoglobin Quin-Hai, beta78 (EF2) leu-to-arg, a new abnormal hemoglobin found in Guangdong, China. Hemoglobin 7: 407-412, 1983. [PubMed: 6629822] [Full Text: https://doi.org/10.3109/03630268309038409]

  530. Jensen, M., Oski, F. A., Nathan, D. G., Bunn, H. F. Hemoglobin Syracuse (beta 143(H21) his-to-pro): a new high-affinity variant detected by special electrophoretic methods--observations on auto-oxidation of normal and variant hemoglobins. J. Clin. Invest. 55: 469-477, 1975. [PubMed: 234980] [Full Text: https://doi.org/10.1172/JCI107953]

  531. Jeppsson, J. O., Kallman, L., Lindgren, G., Fagerstam, L. G. Hb Linkoping (beta36 pro-to-thr): a new hemoglobin mutant characterized by reversed-phase high performance liquid chromatography. J. Chromatogr. 297: 31-36, 1984. [PubMed: 6548480] [Full Text: https://doi.org/10.1016/s0021-9673(01)89026-9]

  532. Johnson, C. S., Moyes, D., Schroeder, W. A., Shelton, J. B., Shelton, J. R., Beutler, E. Hemoglobin Pasadena, beta75(E19) leu-to-arg: identification by high performance liquid chromatography of a new unstable variant with increased oxygen affinity. Biochim. Biophys. Acta 623: 360-367, 1980. [PubMed: 7397219] [Full Text: https://doi.org/10.1016/0005-2795(80)90264-0]

  533. Johnson, M. H., Jue, D. L., Patchen, L. C., Hartwig, E. C., Jr., Schneider, N. J., Moo-Penn, W. F. Hemoglobin Tampa: beta79 (EF3) aspartic acid-to-tyrosine. Biochim. Biophys. Acta 623: 119-123, 1980. [PubMed: 7378467] [Full Text: https://doi.org/10.1016/0005-2795(80)90014-8]

  534. Jones, R. T., Brimhall, B., Gray, G. Hemoglobin British Columbia (beta 101 glu-to-lys), a new variant with high oxygen affinity. Hemoglobin 1: 171-182, 1977. [PubMed: 1052179] [Full Text: https://doi.org/10.3109/03630267608991678]

  535. Jones, R. T., Brimhall, B., Huehns, E. R., Motulsky, A. G. Structural characterization of hemoglobin N (Seattle): beta 61 lys-to-glu. Biochim. Biophys. Acta 154: 278-283, 1968. [PubMed: 5637049] [Full Text: https://doi.org/10.1016/0005-2795(68)90041-x]

  536. Jones, R. T., Brimhall, B., Huisman, T. H. J., Kleihauer, E., Betke, K. Hemoglobin Freiburg: abnormal hemoglobin due to deletion of a single amino acid residue. Science 154: 1024-1027, 1966. [PubMed: 5919752] [Full Text: https://doi.org/10.1126/science.154.3752.1024]

  537. Jones, R. T., Brimhall, B., Pootrakul, S., Gray, G. Hemoglobin Vancouver (beta 73 (E17) asp-to-tyr): its structure and function. J. Molec. Evol. 9: 37-44, 1976. [PubMed: 1018330] [Full Text: https://doi.org/10.1007/BF01796121]

  538. Jones, R. T., Grimes, A. J., Carrell, R. W., Lehmann, H. Koln haemoglobinopathy: further data and a comparison with other hereditary Heinz body anaemias. Brit. J. Haemat. 13: 394-408, 1967. [PubMed: 6067323] [Full Text: https://doi.org/10.1111/j.1365-2141.1967.tb08754.x]

  539. Jones, R. T., Head, C., Shih, M. F.-C., Shih, D. T.-B., Dana, B., Jones, M. B., Koler, R. D. Hemoglobin Linkoping (beta36 (C2) pro-to-thr) in a large Finnish family from Astoria, Oregon, USA. Hemoglobin 10: 455-467, 1986. [PubMed: 3096913] [Full Text: https://doi.org/10.3109/03630268609014131]

  540. Jones, R. T., Koler, R. D., Duerst, M. L., Dhindsa, D. S. Hemoglobin Willamette (alpha-2 beta-2 51 pro-to-arg (D2)): a new abnormal human hemoglobin. Hemoglobin 1: 45-57, 1976. [PubMed: 1052170] [Full Text: https://doi.org/10.3109/03630267609031021]

  541. Jones, R. T., Koler, R. D., Duerst, M., Stocklen, Z. Hemoglobin Casper (gamma 8 beta 106 leu-to-pro): further evidence that hemoglobin mutations are not random. In: Brewer, G. J.: Hemoglobin and Red Cell Structure and Function. Proc. 2nd Int. Conf. on Red Cell Metabolism and Functions. New York: Plenum Press (pub.) 1973.

  542. Jones, R. T., Osgood, E. E., Brimhall, B., Koler, R. D. Hemoglobin Yakima. I. Clinical and biochemical studies. J. Clin. Invest. 46: 1840-1847, 1967. [PubMed: 6061751] [Full Text: https://doi.org/10.1172/JCI105674]

  543. Jones, R. T., Saiontz, H. I., Head, C., Shih, D. T. B., Fairbanks, V. F. Hb Johnstown [beta109(G11)val-to-leu]: a new electrophoretically silent variant that causes erythrocytosis. Hemoglobin 14: 147-156, 1990. [PubMed: 2272838] [Full Text: https://doi.org/10.3109/03630269009046956]

  544. Josephson, A. M., Weinstein, H. G., Yakulis, V. J., Singer, L., Heller, P. A new variant of hemoglobin M disease. Hemoglobin M (Chicago). J. Lab. Clin. Med. 59: 918-925, 1962. [PubMed: 14452533]

  545. Juricic, D., Ruzdic, I., Beer, Z., Efremov, G. D., Casey, R., Lehmann, H. Hemoglobin Leiden (beta6 or 7 (A3 or A4) glu-to-0) in a Yugoslavian woman arisen by a new mutation. Hemoglobin 7: 271-277, 1983. [PubMed: 6874375] [Full Text: https://doi.org/10.3109/03630268309048657]

  546. Kagimoto, T., Morino, Y., Kishimoto, S. A new hemoglobin variant, hemoglobin Yatsushiro (beta 60 val-to-leu). Biochim. Biophys. Acta 532: 195-198, 1978. [PubMed: 620052] [Full Text: https://doi.org/10.1016/0005-2795(78)90463-4]

  547. Kalberer, C. P., Pawliuk, R., Imren, S., Bachelot, T., Takekoshi, K. J., Fabry, M., Eaves, C. J., London, I. M., Humphries, R. K., Leboulch, P. Preselection of retrovirally transduced bone marrow avoids subsequent stem cell gene silencing and age-dependent extinction of expression of human beta-globin in engrafted mice. Proc. Nat. Acad. Sci. 97: 5411-5415, 2000. [PubMed: 10792053] [Full Text: https://doi.org/10.1073/pnas.100082597]

  548. Kamel, K. A., Hoerman, K., Awny, A. Y. Ethnological significance of hemoglobin beta (121 lys). Am. J. Phys. Anthrop. 26: 107-108, 1967. [PubMed: 5633723] [Full Text: https://doi.org/10.1002/ajpa.1330260115]

  549. Kamel, K. A., Hoerman, K. C., Awny, A. Y. 'Hemoglobin alpha2beta2-121lys:' chemical identification in an Egyptian family. Science 156: 397-398, 1967. [PubMed: 5609824] [Full Text: https://doi.org/10.1126/science.156.3773.397]

  550. Kamel, K., El-Najjar, A., Webber, B. B., Chen, S. S., Wilson, J. B., Kutlar, A., Huisman, T. H. J. Hb Doha or beta(X-N-Met-1(NA1)val-to-glu); a new beta-chain abnormal hemoglobin observed in a Qatari female. Biochim. Biophys. Acta 831: 257-260, 1985. [PubMed: 3840039] [Full Text: https://doi.org/10.1016/0167-4838(85)90043-3]

  551. Kan, Y. W., Dozy, A. M., Trecartin, R., Todd, D. Identification of a nondeletion defect in alpha-thalassemia. New Eng. J. Med. 297: 1081-1084, 1977. [PubMed: 909565] [Full Text: https://doi.org/10.1056/NEJM197711172972002]

  552. Kan, Y. W., Dozy, A. M. Antenatal diagnosis of sickle-cell anaemia by DNA analysis of amniotic-fluid cells. Lancet 312: 910-912, 1978. Note: Originally Volume II. [PubMed: 81926] [Full Text: https://doi.org/10.1016/s0140-6736(78)91629-x]

  553. Kan, Y. W., Dozy, A. M. The evolution of the hemoglobin S and C genes in the world population. (Abstract) Clin. Res. 27: 274A, 1979.

  554. Kan, Y. W., Golbus, M. S., Trecartin, R. Prenatal diagnosis of homozygous beta-thalassaemia. Lancet 2: 790-791, 1975. [PubMed: 78154]

  555. Kan, Y. W., Holland, J. P., Dozy, A. M., Charache, S., Kazazian, H., Jr. Deletion of the beta globin structural gene in hereditary persistence of fetal hemoglobin. Nature 258: 162-163, 1975. [PubMed: 1186896] [Full Text: https://doi.org/10.1038/258162a0]

  556. Kan, Y. W., Holland, J. P., Dozy, A. M., Varmus, H. E. Demonstration of non-functional beta globin mRNA in homozygous beta-0 thalassemia. Proc. Nat. Acad. Sci. 72: 5140-5144, 1975. [PubMed: 1061099] [Full Text: https://doi.org/10.1073/pnas.72.12.5140]

  557. Kan, Y. W., Lee, K. Y., Forbetta, M., Angius, A., Cao, A. Polymorphism of DNA sequence in the beta-globin gene region: application to prenatal diagnosis of beta-zero-thalassemia in Sardinia. New Eng. J. Med. 302: 185-188, 1980. [PubMed: 6927915] [Full Text: https://doi.org/10.1056/NEJM198001243020401]

  558. Kaplan, F., Kokotsis, G., DeBraekeleer, M., Morgan, K., Scriver, C. R. Beta-thalassemia genes in French-Canadians: haplotype and mutation analysis of Portneuf chromosomes. Am. J. Hum. Genet. 46: 126-132, 1990. [PubMed: 1967205]

  559. Kattamis, A. C., Kelly, K. M., Ohene-Frempong, K., Reilly, M. P., Keller, M., Cubeddu, R., Adachi, K., Surrey, S., Fortina, P. Hb Osler [beta-145(HC2)tyr-to-asp] results from posttranslational modification. Hemoglobin 21: 109-120, 1997. [PubMed: 9101280] [Full Text: https://doi.org/10.3109/03630269708997515]

  560. Kaufman, R. E., Kretschmer, P. J., Adams, J. W., Coon, H. C., Anderson, W. F., Nienhuis, A. W. Cloning and characterization of DNA sequences surrounding the human gamma-, delta-, and beta-globin genes. Proc. Nat. Acad. Sci. 77: 4229-4233, 1980. [PubMed: 6254016] [Full Text: https://doi.org/10.1073/pnas.77.7.4229]

  561. Kaufman, S., Leiba, H., Clejan, L., Wallis, K., Lorkin, P. A., Lehmann, H. Hemoglobin G-Szuhu, beta-80 asn-to-lys, in the homozygous state in the patient with abetalipoproteinemia. Hum. Hered. 25: 60-68, 1975. [PubMed: 1150295] [Full Text: https://doi.org/10.1159/000152708]

  562. Kavanaugh, J. S., Rogers, P. H., Case, D. A., Arnone, A. High-resolution x-ray study of deoxyhemoglobin Rothschild 37-beta trp-to-arg: a mutation that creates an intersubunit chloride-binding site. Biochemistry 31: 4111-4121, 1992. [PubMed: 1567857] [Full Text: https://doi.org/10.1021/bi00131a030]

  563. Kawata, R., Ohba, Y., Fujisawa, K., Miyaji, T., Tani, Y., Iwasaki, M. Further examples of Hb Takamatsu in Japan. Hemoglobin 13: 89-91, 1989. [PubMed: 2703369] [Full Text: https://doi.org/10.3109/03630268908998057]

  564. Kawata, R., Ohba, Y., Yamamoto, K., Miyaji, T., Makita, R., Ohga, K., Watanabe, S., Miwa, S. Hyperunstable hemoglobin Koriyama: anti-Hb Gun Hill insertion of five residues in the beta chain. Hemoglobin 12: 311-321, 1988. [PubMed: 3170234] [Full Text: https://doi.org/10.3109/03630268808998032]

  565. Kazazian, H. H., Jr., Boehm, C. D. Molecular basis and prenatal diagnosis of beta-thalassemia. Blood 72: 1107-1116, 1988. [PubMed: 3048433]

  566. Kazazian, H. H., Jr., Dowling, C. E., Hurwitz, R. L., Coleman, M., Adams, J. G., III. Thalassemia mutations in exon 3 of the beta-globin gene often cause a dominant form of thalassemia and show no predilection for malarial-endemic regions of the world. (Abstract) Am. J. Hum. Genet. 45: A242, 1989.

  567. Kazazian, H. H., Jr., Dowling, C. E., Hurwitz, R. L., Coleman, M., Stopeck, A., Adams, J. G., III. Dominant thalassemia-like phenotypes associated with mutations in exon 3 of the beta-globin gene. Blood 79: 3014-3018, 1992. [PubMed: 1586746]

  568. Kazazian, H. H., Jr., Fearon, E. R., Waber, P. G., Lee, J. I., Antonarakis, S. E., Orkin, S. H., Vanin, E. F., Heathorn, P. S., Grosveld, F. G., Buchanan, G. R. Gamma-delta-beta thalassemia: deletion of the entire beta-globin gene cluster. (Abstract) Blood 60: 54A, 1982.

  569. Kazazian, H. H., Jr., Orkin, S. H., Antonarakis, S. E., Sexton, J. P., Boehm, C. D., Goff, S. C., Waber, P. G. Molecular characterization of seven beta-thalassemia mutations in Asian Indians. EMBO J. 3: 593-596, 1984. [PubMed: 6714226] [Full Text: https://doi.org/10.1002/j.1460-2075.1984.tb01853.x]

  570. Kazazian, H. H., Jr., Orkin, S. H., Boehm, C. D., Goff, S. C., Wong, C., Dowling, C. E., Newburger, P. E., Knowlton, P. G., Brown, V., Donis-Keller, H. Characterization of a spontaneous mutation to a beta-thalassemia allele. Am. J. Hum. Genet. 38: 860-867, 1986. [PubMed: 3014870]

  571. Kazazian, H. H., Jr., Orkin, S. H., Boehm, C. D., Sexton, J. P., Antonarakis, S. E. Beta-thalassemia due to deletion of the nucleotide which is substituted in sickle cell anemia. Am. J. Hum. Genet. 35: 1028-1033, 1983. [PubMed: 6310991]

  572. Kazazian, H. H., Jr., Waber, P. G., Boehm, C. D., Lee, J. I., Antonarakis, S. E., Fairbanks, V. F. Hemoglobin E in Europeans: further evidence for multiple origins of the beta-E-globin gene. Am. J. Hum. Genet. 36: 212-217, 1984. [PubMed: 6198908]

  573. Kazazian, H. H., Jr. Personal Communication. Baltimore, Md. 1982.

  574. Kazazian, H. H., Jr. Personal Communication. Baltimore, Md. 1989.

  575. Kazazian, H. H., Jr. Personal Communication. Baltimore, Md. 1990.

  576. Kazazian, H. H., Jr. Personal Communication. Baltimore, Md. 1992.

  577. Keclard, L., Campier, A., Merault, G., Auperin, A., Riou, J., Rosa, J., Galacteros, F. Hemoglobin Nevers [beta130(H8)tyr-to-ser]: a new silent variant found in France. Hemoglobin 14: 103-107, 1990. [PubMed: 2384309] [Full Text: https://doi.org/10.3109/03630269009002258]

  578. Keeling, M. M., Bertolone, S. J., Baysal, E., Gu, Y.-C., Cepreganova, B., Wilson, J. B., Huisman, T. H. J. Hb Mizuho or beta68(E12)leu-to-pro in a Caucasian boy with high levels of Hb F: identification by sequencing of amplified DNA. Hemoglobin 15: 477-485, 1991. [PubMed: 1726094] [Full Text: https://doi.org/10.3109/03630269109027895]

  579. Keeling, M. M., Ogden, L. L., Wrightstone, R. N., Wilson, J. B., Reynolds, C. A., Kitchens, J. L., Huisman, T. H. J. Hemoglobin Louisville (beta 42 (CD1) phe-to-leu): an unstable variant causing mild hemolytic anemia. J. Clin. Invest. 50: 2395-2402, 1971. [PubMed: 5096522] [Full Text: https://doi.org/10.1172/JCI106738]

  580. Kendall, A. G., ten Pas, A., Wilson, J. B., Cope, N., Bolch, K., Huisman, T. H. J. Hb Vaasa or beta 39: gln-to-glu, a mildly unstable variant found in a Finnish family. Hemoglobin 1: 292-295, 1977. [PubMed: 893132] [Full Text: https://doi.org/10.3109/03630267709003413]

  581. Kendall, A., Pang, W. Hemoglobin New York associated with alpha-thalassemia. Hum. Hered. 30: 50-53, 1980. [PubMed: 7353889] [Full Text: https://doi.org/10.1159/000153089]

  582. Kendall, A., Young, S., Oune, N., Wiltshire, B., Lehmann, H. The unstable Hb Genova (beta 28 leu-to-pro) in a East African family: family study and the effect of splenectomy. Acta Haemat. 61: 278-282, 1979. [PubMed: 111455] [Full Text: https://doi.org/10.1159/000207672]

  583. Kennedy, C. C., Blundell, G., Lorkin, P. A., Lang, A., Lehmann, H. Hemoglobin Belfast 15(A12) trp-to-arg: a new unstable hemoglobin variant. Brit. Med. J. 4: 324-326, 1974. [PubMed: 4434089] [Full Text: https://doi.org/10.1136/bmj.4.5940.324]

  584. Keser, I., Kayisli, O. G., Yesilipek, A., Ozes, O. N., Luleci, G. Hb Anatalya (codons 3-5 (Leu-Thr-Pro-to-Ser-Asp-Ser)): A new unstable variant leading to chronic microcytic anemia and high Hb A2. Hemoglobin 25: 369-373, 2001. [PubMed: 11791869] [Full Text: https://doi.org/10.1081/hem-100107873]

  585. Kiger, L., Kister, J., Groff, P., Kalmes, G., Prome, D., Galacteros, F., Wajcman, H. Hb J-Europa [beta-62(E6)ala-to-asp]: normal oxygen binding properties in a new variant involving a residue located distal to the heme. Hemoglobin 20: 135-140, 1996. [PubMed: 8811317] [Full Text: https://doi.org/10.3109/03630269609027919]

  586. Kim, J. Y., Park, S. S., Jung, H. L., Keum, D. H., Park, H., Chang, Y. H., Lee, Y. J., Cho, H. I. Hb Madrid (beta-115(G17)ala-to-pro) in a Korean family with chronic hemolytic anemia. Hemoglobin 24: 133-138, 2000. [PubMed: 10870884] [Full Text: https://doi.org/10.3109/03630260009003432]

  587. Kim, J. Y., Park, S. S., Yang, S. H., Joo, S.-I., Lee, Y. J., Ra, E. K., Shin, S., Kim, E. C., Cho, H.-I. A Korean family with a dominantly inherited beta-thalassemia due to Hb Durham-N.C./Brescia (beta-114(G16)leu-to-pro). Hemoglobin 25: 79-89, 2001. [PubMed: 11300352] [Full Text: https://doi.org/10.1081/hem-100103072]

  588. Kimura, A., Matsunaga, E., Takihara, Y., Nakamura, T., Takagi, Y. Structural analysis of a beta-thalassemia gene found in Taiwan. J. Biol. Chem. 258: 2748-2749, 1983. [PubMed: 6826539]

  589. Kimura, A., Ohta, Y., Fukumaki, Y., Takagi, Y. A fusion gene in man: DNA sequence analysis of the abnormal globin gene of hemoglobin Miyada. Biochem. Biophys. Res. Commun. 119: 968-974, 1984. [PubMed: 6324786] [Full Text: https://doi.org/10.1016/0006-291x(84)90868-4]

  590. Kimura, E. M., Jorge, S. B., Ogo, S. H., Cesquini, M., Albuquerque, D. M., Fattori, A., Saad, S. T. O., Costa, F. F., Sonati, M. F. A novel beta-globin variant: Hb Pocos de Caldas (beta-61(E5)lys-to-gln). Hemoglobin 26: 385-388, 2002. [PubMed: 12484633] [Full Text: https://doi.org/10.1081/hem-120016375]

  591. King, M. A. R., Wiltshire, B. G., Lehmann, H., Morimoto, H. An unstable haemoglobin with reduced oxygen affinity: haemoglobin Peterborough, beta 111 (G13) valine to phenylalanine, its interaction with normal haemoglobin and with haemoglobin Lepore. Brit. J. Haemat. 22: 125-134, 1972. [PubMed: 5057941] [Full Text: https://doi.org/10.1111/j.1365-2141.1972.tb08794.x]

  592. Kinniburgh, A. J., Maquat, L. E., Schedl, T., Rachmilewitz, E., Ross, J. mRNA deficient beta-0-thalassemia results from a single nucleotide deletion. Nucleic Acids Res. 10: 5421-5427, 1982. [PubMed: 6292840] [Full Text: https://doi.org/10.1093/nar/10.18.5421]

  593. Kister, J., Prehu, C., Riou, J., Godart, C., Bardakdjian, J., Prome, D., Galacteros, F., Wajcman, H. Two hemoglobin variants with an alteration of the oxygen-linked chloride binding: Hb Antananarivo [alpha1(NA1)val-to-gly] and Hb Barbizon [beta144(HC1)lys-to-met]. Hemoglobin 23: 21-32, 1999. [PubMed: 10081983] [Full Text: https://doi.org/10.3109/03630269908996145]

  594. Kleckner, H. B., Wilson, J. B., Lindeman, J. G., Stevens, P. D., Naizi, G., Hunter, E., Chen, C. J., Huisman, T. H. J. Hemoglobin Fort Gordon (beta 145 tyr-to-asp), a new high-oxygen-affinity hemoglobin variant. Biochim. Biophys. Acta 400: 343-347, 1975. [PubMed: 1164510] [Full Text: https://doi.org/10.1016/0005-2795(75)90189-0]

  595. Kobayashi, S., Nara, T., Nakano, Y., Fukazawa, H., Kawamura, G., Kitajima, H., Sugita, M., Joh, K., Ohba, Y., Hattori, Y., Miyaji, T. Hemoglobin Burke: an unstable hemoglobin rarely associated with hemolytic episodes. Hemoglobin 10: 661-666, 1986. [PubMed: 3557997] [Full Text: https://doi.org/10.3109/03630268609036570]

  596. Kobayashi, Y., Fukumaki, Y., Komatsu, N., Ohba, Y., Miyaji, T., Miura, Y. A novel globin structural mutant, Showa-Yakushiji (beta-110 leu-to-pro) causing a beta-thalassemia phenotype. Blood 70: 1688-1691, 1987. [PubMed: 2822177]

  597. Kohen, G., Philippe, N., Godet, J. Polymorphism of the HindI restriction site located 1 kb 5-prime to the human beta-globin gene. Hum. Genet. 62: 121-123, 1982. [PubMed: 6298094] [Full Text: https://doi.org/10.1007/BF00282298]

  598. Kohne, E., Grosse, H. P., Versmold, H., Kley, H. P., Kleihauer, E. Hb M Erlangen: beta 63 (E7) tyr. Eine neue Mutation mit Haemolyse und Diaphorasemangel. Z. Kinderheilk. 120: 69-78, 1975. [PubMed: 1163074]

  599. Kohne, E., Kley, H. P., Kleihauer, E. Structural and functional characteristics of the Hb Tubingen: beta 106 (G8) leu-to-gln. FEBS Lett. 64: 443-447, 1976. [PubMed: 1278400] [Full Text: https://doi.org/10.1016/0014-5793(76)80346-8]

  600. Kohne, E., Wendt, F.-K., Kleinhauer, E. Hb M Milwaukee in a German family. Hemoglobin 1: 759-769, 1977. [PubMed: 604314] [Full Text: https://doi.org/10.3109/03630267709003905]

  601. Koler, R. D., Jones, R. T., Bigley, R. H., Litt, M., Lovrien, E., Brooks, R., Lahey, M. E., Fowler, R. Hemoglobin Casper: beta 106 (gamma 8) leu-to-pro: a contemporary mutation. Am. J. Med. 55: 549-558, 1973. [PubMed: 4743351] [Full Text: https://doi.org/10.1016/0002-9343(73)90213-1]

  602. Kollia, P., Gonzalez-Redondo, J. M., Stoming, T. A., Loukopoulos, D., Politis, C., Huisman, T. H. J. Frameshift codon 5 [FSC-5 (-CT)] thalassemia: a novel mutation detected in a Greek patient. Hemoglobin 13: 597-604, 1989. [PubMed: 2606727] [Full Text: https://doi.org/10.3109/03630268908993110]

  603. Konotey-Ahulu, F. I. D., Gallo, E., Lehmann, H., Ringelhann, B. Haemoglobin Korle-Bu (beta 73 aspartic acid to asparagine) showing one of the two amino acid substitutions of haemoglobin C Harlem. J. Med. Genet. 5: 107-111, 1968. [PubMed: 5722880] [Full Text: https://doi.org/10.1136/jmg.5.2.107]

  604. Konotey-Ahulu, F. I. D., Kinderlerer, J. L., Lehmann, H., Ringelhann, B. Haemoglobin Osu-Christiansborg: a new beta-chain variant of haemoglobin A (beta 52(D3) aspartic acid-to-asparagine) in combination with haemoglobin S. J. Med. Genet. 8: 302-305, 1971. [PubMed: 5097135] [Full Text: https://doi.org/10.1136/jmg.8.3.302]

  605. Koop, B. F., Goodman, M., Xu, P., Chan, K., Slightom, J. L. Primate eta-globin DNA sequences and man's place among the great apes. Nature 319: 234-238, 1986. [PubMed: 3945312] [Full Text: https://doi.org/10.1038/319234a0]

  606. Kosugi, H., Weinstein, A. S., Kikugawa, K., Asakura, T. Characterization and properties of Hb York (beta146 his-to-pro). Hemoglobin 7: 205-226, 1983. [PubMed: 6874372] [Full Text: https://doi.org/10.3109/03630268309048651]

  607. Krawczak, M., Ball, E. V., Fenton, I., Stenson, P. D., Abeysinghe, S., Thomas, N., Cooper, D. N. Human gene mutation database--a biomedical information and research resource. Hum. Mutat. 15: 45-51, 2000. [PubMed: 10612821] [Full Text: https://doi.org/10.1002/(SICI)1098-1004(200001)15:1<45::AID-HUMU10>3.0.CO;2-T]

  608. Krawczak, M., Reiss, J., Cooper, D. N. The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences. Hum. Genet. 90: 41-54, 1992. [PubMed: 1427786] [Full Text: https://doi.org/10.1007/BF00210743]

  609. Krishnan, K., Martinez, F., Cooney, K., Jones, R. T., Shih, D. T., Dabich, L. Co-inheritance of a low oxygen affinity hemoglobin, Hb Washtenaw, beta11 (A8) val-to-phe and primary pulmonary hypertension in a Hungarian-American kindred. (Abstract) Blood 82 (suppl. 1): 471a, 1993.

  610. Krishnan, K., Martinez, F., Wille, R. T., Jones, R. T., Shih, D. T., Head, C., Fairbanks, V. F., Dabich, L. Hb Washtenaw (beta-11(A8) val-to-phe): an electrophoretically silent, unstable, low oxygen affinity variant associated with anemia and chronic cyanosis. Hemoglobin 18: 285-295, 1994. [PubMed: 7852083] [Full Text: https://doi.org/10.3109/03630269408996194]

  611. Kuis-Reerink, J. D., Jonxis, J. H., Niazi, G. A., Wilson, J. B., Bolch, K. C., Gravely, M., Huisman, T. H. Hb-Volga or alpha-2 beta-2 27(B9) ala replaced by asp: an unstable hemoglobin variant in three generations of a Dutch family. Biochim. Biophys. Acta 439: 63-69, 1976. [PubMed: 952960] [Full Text: https://doi.org/10.1016/0005-2795(76)90161-6]

  612. Kulozik, A. E., Wainscoat, J. S., Serjeant, G. R., Kar, B. C., Al-Awamy, B., Essan, G. J. F., Falusi, A. G., Haque, S. K., Hilali, A. M., Kate, S., Ranasinghe, W. A. E. P., Weatherall, D. J. Geographical survey of beta-S-globin gene haplotypes: evidence for an independent Asian origin of the sickle-cell mutation. Am. J. Hum. Genet. 39: 239-244, 1986. [PubMed: 3752087]

  613. Kulozik, A. E., Yarwood, N., Jones, R. W. The Corfu delta-beta-zero thalassemia: a small deletion acts at a distance to selectively abolish beta globin gene expression. Blood 71: 457-462, 1988. Note: Erratum: 71: 1509 only, 1988. [PubMed: 2827815]

  614. Kurachi, S., Hermodson, M., Hornung, S., Stamatoyannopoulos, G. Structure of haemoglobin Seattle. Nature N.B. 243: 275-276, 1973. [PubMed: 4515495] [Full Text: https://doi.org/10.1038/newbio243275a0]

  615. Kutlar, A., Kutlar, F., Aksoy, M., Gurgey, A., Altay, C., Wilson, J. B., Diaz-Chico, J. C., Hu, H., Huisman, T. H. J. Beta-thalassemia intermedia in two Turkish families is caused by the interaction of Hb Knossos (beta27 (B9) ala-to-ser) and of Hb City of Hope (beta69 (E13) gly-to-ser) with beta-zero-thalassemia. Hemoglobin 13: 7-16, 1989. [PubMed: 2467892] [Full Text: https://doi.org/10.3109/03630268908998049]

  616. Kutlar, F., Felice, A. E., Grech, J. L., Bannister, W. H., Kutlar, A., Wilson, J. B., Webber, B. B., Hu, H., Huisman, T. H. J. The linkage of Hb Valletta (beta-87(F3)thr-to-pro) and Hb F-Malta-I (G-gamma-117(G19)his-to-arg) in the Maltese population. Hum. Genet. 86: 591-594, 1991. [PubMed: 1709134] [Full Text: https://doi.org/10.1007/BF00201546]

  617. Kwiatkowski, D. P. How malaria has affected the human genome and what human genetics can teach us about malaria. Am. J. Hum. Genet. 77: 171-192, 2005. [PubMed: 16001361] [Full Text: https://doi.org/10.1086/432519]

  618. Kyrri, A., Felekis, X., Kalogerou, E., Christopoulos, G., Makariou, C., Loizidou, D., Kleanthous, M. Hb Limassol (beta-8(A5)lys-to-asn): a new hemoglobin variant. Hemoglobin 25: 421-424, 2001. [PubMed: 11791876] [Full Text: https://doi.org/10.1081/hem-100107880]

  619. Labie, D., Bernadou, A., Wajcman, H., Bilski-Pasquier, G. A familial observation of hemoglobin Genova (beta 28 (B10) leu-to-pro). A hematological, genetic and biochemical clinical study of a French family. Nouv. Rev. Franc. Hemat. 12: 502-505, 1972. [PubMed: 4264206]

  620. Labie, D., Rosa, J., Belkhodja, O., Bierme, R. Hemoglobin Toulouse beta66 (E10)lys-to-glu: structure and consequences in molecular pathology. Biochim. Biophys. Acta 236: 201-207, 1971. [PubMed: 5577462]

  621. Labossiere, A., Hill, J. R., Vella, F. A new B-TP V hemoglobin variant: Hb Edmonton. Clin. Biochem. 4: 114-117, 1971. [PubMed: 5128293] [Full Text: https://doi.org/10.1016/s0009-9120(71)90893-9]

  622. Labossiere, A., Vella, F., Hiebert, J., Galbraith, P. Hemoglobin Deer Lodge: beta2 his-to-arg. Clin. Biochem. 5: 46-50, 1972. [PubMed: 5022448] [Full Text: https://doi.org/10.1016/s0009-9120(72)80007-9]

  623. Lacan, P., Badens, C., Lena-Russo, D., Merono, F., Thuret, I., Aubry, M., Couprie, N., Francina, A. Hb Aubagne [beta-64(E8)gly-to-ala]: a new unstable beta chain variant found in a French family. Hemoglobin 26: 163-167, 2002. [PubMed: 12144059] [Full Text: https://doi.org/10.1081/hem-120005454]

  624. Lacan, P., Becchi, M., Zanella-Cleon, I., Aubry, M., Ffrench, M., Couprie, N., Francina, A. Two new beta chain variants: Hb Tripoli [beta-26(B8)glu-to-ala] and Hb Tizi-Ouzou [beta-29(B11)gly-to-ser]. Hemoglobin 28: 205-212, 2004. [PubMed: 15481887] [Full Text: https://doi.org/10.1081/hem-120040313]

  625. Lacan, P., Francina, A., Prome, D., Delaunay, J., Galacteros, F., Wajcman, H. Hb Aubenas [beta-26(B8)glu-to-gly]: a new variant normally synthesized, affecting the same codon as in Hb E. Hemoglobin 20: 113-124, 1996. [PubMed: 8811314] [Full Text: https://doi.org/10.3109/03630269609027916]

  626. Lacan, P., Kister, J., Francina, A., Souillet, G., Galacteros, F., Delaunay, J., Wajcman, H. Hemoglobin Debrousse (beta-96-(FG3)leu-to-pro): a new unstable hemoglobin with twofold increased oxygen affinity. Am. J. Hemat. 51: 276-281, 1996. [PubMed: 8602627] [Full Text: https://doi.org/10.1002/(SICI)1096-8652(199604)51:4<276::AID-AJH5>3.0.CO;2-T]

  627. Lacan, P., Moreau, M., Becchi, M., Zanella-Cleon, I., Aubry, M., Louis, J.-J., Couprie, N., Francina, A. Two new hemoglobin variants: Hb Brem-sur-Mer (beta-9(A6)ser-to-tyr) and Hb Passy (alpha-81(F2)ser-to-pro (alpha-2)). Hemoglobin 29: 69-75, 2005. [PubMed: 15768558]

  628. Lacombe, C., Arous, N., Pontet, F., Blouquit, Y., Bardakdjian, J., Riou, J., Rousselet, F., Galacteros, F. Hb I-High Wycombe (beta59 (E3) lys-to-glu) in a woman of Malian origin. Hemoglobin 11: 173-176, 1987. [PubMed: 3114176] [Full Text: https://doi.org/10.3109/03630268709005794]

  629. Lacombe, C., Blouquit, Y., Arous, N., Riou, J., Harousseau, J. L., Bardakdjian, J., Milpied, N., Galacteros, F. Hb Potomac (beta101 (G3) glu-to-asp) in a Polish family living in France. Hemoglobin 11: 55-59, 1987. [PubMed: 3583767] [Full Text: https://doi.org/10.3109/03630268709036584]

  630. Lacombe, C., Craescu, C. T., Blouquit, Y., Kister, J., Poyart, C., Delanoe-Garin, J., Arous, N., Bardakdjian, J., Riou, J., Rosa, J., Schaeffer, C., Galacteros, F. Structural and functional studies of hemoglobin Poissy beta56 (D7) gly-to-arg and beta86 ala-to-pro. Europ. J. Biochem. 153: 655-662, 1985. [PubMed: 3841063] [Full Text: https://doi.org/10.1111/j.1432-1033.1985.tb09350.x]

  631. Lacombe, C., Prome, D., Blouquit, Y., Bardakdjian, J., Arous, N., Mrad, A., Prome, J.-C., Rosa, J. New results of hemoglobin variant structure determinations by fast atom bombardment mass spectrometry. Hemoglobin 14: 529-548, 1990. [PubMed: 2079433] [Full Text: https://doi.org/10.3109/03630269009005806]

  632. Lafferty, J., Ali, M., Matthew, K., Eng, B., Patterson, M., Waye, J. S. Identification of a new high oxygen affinity hemoglobin variant: Hb Aurora [beta-139(H17)asn-to-tyr]. Hemoglobin 19: 335-341, 1995. [PubMed: 8718692] [Full Text: https://doi.org/10.3109/03630269509005825]

  633. Laig, M., Sanguansermsri, T., Wiangnon, S., Hundrieser, J., Pape, M., Flatz, G. The spectrum of beta-thalassemia mutations in northern and northeastern Thailand. Hum. Genet. 84: 47-50, 1989. [PubMed: 2606477] [Full Text: https://doi.org/10.1007/BF00210669]

  634. Lam, H., Wilson, J. B., Harris, H., Gravely, M., Huisman, T. H. J. Hemoglobin Alamo (beta 19 (B1) asn-to-asp). Hemoglobin 1: 703-706, 1977. [PubMed: 914645] [Full Text: https://doi.org/10.3109/03630267708999177]

  635. Lambotte-Legrand, J., Lambotte-Legrand, C., Ager, J. A., Lehmann, H. L'hemoglobinose P: a propos d'un cas d'association des hemoglobines P et S. Rev. Hemat. 15: 10-18, 1960. [PubMed: 14413637]

  636. Lanclos, K. D., Patterson, J., Efremov, G. D., Wong, S. C., Villegas, A., Ojwang, P. J., Wilson, J. B., Kutlar, F., Huisman, T. H. J. Characterization of chromosomes with hybrid genes for Hb Lepore-Washington, Hb Lepore-Baltimore, Hb P-Nilotic, and Hb Kenya. Hum. Genet. 77: 40-45, 1987. [PubMed: 2442092] [Full Text: https://doi.org/10.1007/BF00284711]

  637. Landin, B., Berglund, S., Lindoff, B. Hb Trollhaettan [beta-20 (B2) val-to-glu]--a new haemoglobin variant with increased oxygen affinity causing erythrocytosis. Europ. J. Haemat. 53: 21-25, 1994. [PubMed: 7914875]

  638. Landin, B., Berglund, S., Wallman, K. Two different mutations in codon 97 of the beta-globin gene cause Hb Malmo in Sweden. Am. J. Hemat. 51: 32-36, 1996. [PubMed: 8571935] [Full Text: https://doi.org/10.1002/(SICI)1096-8652(199601)51:1<32::AID-AJH6>3.0.CO;2-8]

  639. Landin, B., Frostad, B., Brune, M., Ljung, R. Haemoglobin Koln as de novo mutations in Sweden: diagnosis by PCR and specific enzymatic cleavage. Europ. J. Haemat. 52: 156-161, 1994. [PubMed: 8168595] [Full Text: https://doi.org/10.1111/j.1600-0609.1994.tb01307.x]

  640. Landin, B., Rudolphi, O., Ek, B. Initiation codon mutation (ATG-ATA) of the beta-globin gene causing beta-thalassemia in a Swedish family. Am. J. Hemat. 48: 158-162, 1995. [PubMed: 7864023] [Full Text: https://doi.org/10.1002/ajh.2830480304]

  641. Landin, B. Hb Karlskoga or beta21 (B3) asp-to-his: a new slow-moving variant found in Sweden. Hemoglobin 17: 201-208, 1993. [PubMed: 8330972] [Full Text: https://doi.org/10.3109/03630269308998894]

  642. Landman, H., Wilson, J. B., Kutlar, A., Gonzalez Redondo, J. M., Huisman, T. H. J. Hb G-Taipei or beta22 (B4) glu-to-gly in a Chinese family living in the Netherlands. Hemoglobin 11: 169-171, 1987. [PubMed: 3623978] [Full Text: https://doi.org/10.3109/03630268709005793]

  643. Lane, P. A., Rogers, Z. R., Woods, G. M., Wang, W. C., Wilimas, J. A., Miller, S. T., Khakoo, Y., Buchanan, G. R. Fatal pneumococcal septicemia in hemoglobin SC disease. J. Pediat. 124: 859-862, 1994. [PubMed: 8201467] [Full Text: https://doi.org/10.1016/s0022-3476(05)83171-3]

  644. Lang, A., Lehmann, H., McCurdy, P. R., Pierce, L. Identification of haemoglobin C Georgetown. Biochim. Biophys. Acta 278: 57-61, 1972. [PubMed: 5069596] [Full Text: https://doi.org/10.1016/0005-2795(72)90106-7]

  645. Langdown, J. V., Williamson, D., Beresford, C. H., Gibb, I., Taylor, R., Deacon-Smith, R. A new beta chain variant, Hb Tyne (beta-5 (A2) pro-to-ser). Hemoglobin 18: 333-336, 1994. [PubMed: 7852088] [Full Text: https://doi.org/10.3109/03630269408996199]

  646. Langdown, J. V., Williamson, D., Knight, C. B., Rubenstein, D., Carrell, R. W. A new doubly substituted sickling haemoglobin: HbS-Oman. Brit. J. Haemat. 71: 443-444, 1989. [PubMed: 2930724] [Full Text: https://doi.org/10.1111/j.1365-2141.1989.tb04304.x]

  647. Lapoumeroulie, C., Dunda, O., Ducrocq, R., Trabuchet, G., Mony-Lobe, M., Bodo, J. M., Carnevale, P., Labie, D., Elion, J., Krishnamoorthy, R. A novel sickle cell mutation of yet another origin in Africa: the Cameroon type. Hum. Genet. 89: 333-337, 1992. [PubMed: 1376298] [Full Text: https://doi.org/10.1007/BF00220553]

  648. Lapoumeroulie, C., Pagnier, J., Bank, A., Labie, D., Krishnamoorthy, R. Beta-thalassemia due to a novel mutation in IVS-1 sequence donor site consensus sequence creating a restriction site. Biochem. Biophys. Res. Commun. 139: 709-713, 1986. [PubMed: 3021139] [Full Text: https://doi.org/10.1016/s0006-291x(86)80048-1]

  649. Lau, Y.-L., Chan, L.-C., Chan, Y.-Y. A., Ha, S.-Y., Yeung, C.-Y., Waye, J. S., Chui, D. H. K. Prevalence and genotypes of alpha- and beta-thalassemia carriers in Hong Kong: implications for population screening. New Eng. J. Med. 336: 1298-1301, 1997. [PubMed: 9113933] [Full Text: https://doi.org/10.1056/NEJM199705013361805]

  650. Lawn, R. M., Efstratiadis, A., O'Connell, C. O., Maniatis, T. The nucleotide sequence of the human beta-globin gene. Cell 21: 647-651, 1980. [PubMed: 6254664] [Full Text: https://doi.org/10.1016/0092-8674(80)90428-6]

  651. Lebo, R. V., Carrano, A. V., Burkhart-Schultz, K., Dozy, A. M., Yu, C.-C., Kan, Y. W. Assignment of human beta-, gamma-, and delta-globin genes to the short arm of chromosome 11 by chromosome sorting and DNA restriction enzyme analysis. Proc. Nat. Acad. Sci. 76: 5804-5808, 1979. [PubMed: 293684] [Full Text: https://doi.org/10.1073/pnas.76.11.5804]

  652. Lebo, R. V., Cheung, M.-C., Bruce, B. D., Riccardi, V. M., Kao, F.-T., Kan, Y. W. Mapping parathyroid hormone, beta-globin, insulin, and LDH-A genes within the human chromosome 11 short arm by spot blotting sorted chromosomes. Hum. Genet. 69: 316-320, 1985. [PubMed: 2985490] [Full Text: https://doi.org/10.1007/BF00291648]

  653. Lebo, R. V., Kan, Y. W., Cheung, M. C., Cordell, B., Goodman, H. M., Law, M. L., Jones, C., Kao, F. T. Assignment of the human insulin gene to chromosome 11 band p11 and linkage analysis with the beta-globin locus. (Abstract) Am. J. Hum. Genet. 33: 150A, 1981.

  654. Lehmann, H., Beale, D., Boi-Doku, F. S. Haemoglobin G (Accra). Nature 203: 363-365, 1964. [PubMed: 14197371] [Full Text: https://doi.org/10.1038/203363a0]

  655. Lehmann, H., Carrell, R. W. Variations in the structure of human haemoglobins: with particular reference to the unstable haemoglobins. Brit. Med. Bull. 25: 14-23, 1969. [PubMed: 5782754] [Full Text: https://doi.org/10.1093/oxfordjournals.bmb.a070664]

  656. Lehmann, H., Charlesworth, D. Observations on haemoglobin P (Congo type). Biochem. J. 119: 43P, 1970. [PubMed: 5492814] [Full Text: https://doi.org/10.1042/bj1190043pa]

  657. Lehmann, H. Haemolyse aufgrund instabiler Haemoglobine. In: Nowicki, L.; Martin, H.; Schubert, J. C. F. (eds.): Haemolyse-haemolytische Erkrankungen. Munich: J. F. Lehmanns Verlag (pub.) 1973.

  658. Lehmann, H. Hemoglobin Coventry, a beta-delta chain? In: Brewer, G. J. (ed.): The Red Cell. New York: Alan R. Liss (pub.) 1978. Pp. 83-89.

  659. Lena-Russo, D., Orsini, A., Vovan, L., Bardakdjian-Michau, J., Lacombe, C., Blouquit, Y., Craescu, C. T., Galacteros, F. Hemoglobin N-Timone (beta8(A5)lys-to-glu): a new fast-moving variant with normal stability and oxygen affinity. Hemoglobin 13: 743-747, 1989. [PubMed: 2634671] [Full Text: https://doi.org/10.3109/03630268908998848]

  660. Lewis, J., Yang, B., Kim, R., Sierakowska, H., Kole, R., Smithies, O., Maeda, N. A common human beta globin splicing mutation modeled in mice. Blood 91: 2152-2156, 1998. [PubMed: 9490703]

  661. Li, H. J., Liu, D. X., Li, L., Liu, Z. G., Lo, S. L., Zhao, J., Han, X. P., Yu, W. Z. A note about the incidence and origin of Hb D-Punjab in Xinjiang, People's Republic of China. Hemoglobin 10: 667-671, 1986. [PubMed: 3557998] [Full Text: https://doi.org/10.3109/03630268609036571]

  662. Li, H. J., Zhao, X. N., Li, H. W., Li, L., Liang, K. X., Wang, R. P., Chang, T. T., Wilson, J. B., Webber, B. B., Huisman, T. H. J. A new slow-moving hemoglobin variant Hb Tianshui or beta39(C5)gln-to-arg, observed in a Chinese family living in Gansu. Hemoglobin 14: 569-570, 1990. [PubMed: 2079437] [Full Text: https://doi.org/10.3109/03630269009005810]

  663. Li, H., Zhao, X., Qin, F., Li, H., Li, L., He, X., Chang, X., Li, Z., Liang, K., Xing, F., Chang, W., Wong, R., Yang, I., Li, F., Zhang, T., Tian, R., Webber, B. B., Wilson, J. B., Huisman, T. H. J. Abnormal hemoglobins in the Silk Road region of China. Hum. Genet. 86: 231-235, 1990. [PubMed: 2265836] [Full Text: https://doi.org/10.1007/BF00197711]

  664. Li, W., Hattori, Y., Ohba, Y., Okayama, N., Lin, W. S., Long, G. F., Yamashiro, Y., Yamamoto, K., Yamamoto, K. Another example of the beta-thalassemia mutation, IVS-I(-2) or codon 30 (A-G), found in a Chinese family. Hemoglobin 22: 377-381, 1998. [PubMed: 9730368] [Full Text: https://doi.org/10.3109/03630269809071532]

  665. Lie-Injo, L. E., Lopez, C. G., Eapen, J. S., Eravelly, J., Wiltshire, B. G., Lehmann, H. Unstable haemoglobin Koln disease in members of a Malay family. J. Med. Genet. 9: 340-343, 1972. [PubMed: 5079107] [Full Text: https://doi.org/10.1136/jmg.9.3.340]

  666. Lin, C. C., Draper, P. N., De Braekeleer, M. High-resolution chromosomal localization of the beta-gene of the human beta-globin gene complex by in situ hybridization. Cytogenet. Cell Genet. 39: 269-274, 1985. [PubMed: 4053691] [Full Text: https://doi.org/10.1159/000132156]

  667. Lin, L.-I., Lin, K.-S., Lin, K.-H., Cheng, T.-Y. A novel -32 (C-A) mutant identified in amplified genomic DNA of a Chinese beta-thalassemic patient. (Letter) Am. J. Hum. Genet. 50: 237-238, 1992. [PubMed: 1729892]

  668. Little, P. F. R., Whitelaw, E., Annison, G., Williamson, R., Kooter, J. M., Flavell, R. A., Goossens, M., Sergeant, G. R., Montgomery, D. The detection and use of hemoglobin mutants in the direct analysis of human globin genes. Blood 55: 1060-1062, 1980. [PubMed: 6246994]

  669. Liu, J.-S., Molchanova, T. P., Gu, L.-H., Wilson, J. B., Hopmeier, P., Schnedl, W., Balaun, E., Krejs, G. J., Huisman, T. H. J. Hb Graz or beta-2 (NA2) his-to-leu: a new beta chain variant observed in four families from southern Austria. Hemoglobin 16: 493-501, 1992. [PubMed: 1487420] [Full Text: https://doi.org/10.3109/03630269208993117]

  670. Lo, Y. M. D., Hjelm, N. M., Fidler, C., Sargent, I. L., Murphy, M. F., Chamberlain, P. F., Poon, P. M. K., Redman, C. W. G., Wainscoat, J. S. Prenatal diagnosis of fetal RhD status by molecular analysis of maternal plasma. New Eng. J. Med. 339: 1734-1738, 1998. [PubMed: 9845707] [Full Text: https://doi.org/10.1056/NEJM199812103392402]

  671. Lokich, J. J., Moloney, W. C., Bunn, H. F., Bruckheimer, S. M., Ranney, H. M. Hemoglobin Brigham (beta 100 pro-to-leu). Hemoglobin variant associated with familial erythrocytosis. J. Clin. Invest. 52: 2060-2067, 1973. [PubMed: 4719677] [Full Text: https://doi.org/10.1172/JCI107390]

  672. Lorkin, P. A., Lehmann, H. Two new pathological haemoglobins: Olmsted beta 141 (H19) leu leads to arg and Malmo beta 97 (FG4) his leads to gln. Biochem. J. 119: 38P, 1970.

  673. Lorkin, P. A., Pietschmann, H., Braunsteiner, H., Lehmann, H. Structure of haemoglobin Wien beta-130 (H8) tyrosine-aspartic acid; an unstable haemoglobin variant. Acta Haemat. 51: 351-361, 1974. [PubMed: 4212355] [Full Text: https://doi.org/10.1159/000208318]

  674. Lorkin, P. A., Stephens, A. D., Beard, M. E. J., Wrigley, D. F. M., Adams, L., Lehmann, H. Haemoglobin Rahere (beta 82 lys-to-thr): a new high affinity haemoglobin associated with decreased 2,3-diphosphoglycerate binding and relative polycythaemia. Brit. Med. J. 4: 200-202, 1975. [PubMed: 124] [Full Text: https://doi.org/10.1136/bmj.4.5990.200]

  675. Losekoot, M., Fodde, R., Harteveld, C. L., van Heeren, H., Giordano, P. C., Went, L. N., Bernini, L. F. Homozygous beta(+) thalassaemia owing to a mutation in the cleavage-polyadenylation sequence of the human beta globin gene. J. Med. Genet. 28: 252-255, 1991. [PubMed: 1856830] [Full Text: https://doi.org/10.1136/jmg.28.4.252]

  676. Losekoot, M., Fodde, R., van Heeren, H., Harteveld, C. L., Giordano, P. C., Bernini, L. F. A novel frameshift mutation [FSC 47 (+A)] causing beta-thalassemia in a Surinam patient. Hemoglobin 14: 467-470, 1990. [PubMed: 2283303] [Full Text: https://doi.org/10.3109/03630269009032010]

  677. Losekoot, M., van Heeren, H., Schipper, J. J., Giordano, P. C., Bernini, L. F., Fodde, R. Rapid detection of the highly polymorphic beta globin framework by denaturing gradient gel electrophoresis. J. Med. Genet. 29: 574-577, 1992. [PubMed: 1355561] [Full Text: https://doi.org/10.1136/jmg.29.8.574]

  678. Lu, Y.-Q., Fan, J.-L., Liu, J.-F., Hu, H.-L., Peng, X.-H., Huang, C.-H., Huang, P.-Y., Chen, S.-S., Jia, P.-C., Yang, K.-G., Liang, C.-C., Ren, X.-D., Zuo, C.-R. Hemoglobin Jianghua (beta120(GH3) lys-to-ile): a new fast-moving variant found in China. Hemoglobin 7: 321-326, 1983. [PubMed: 6618888]

  679. Lutcher, C. L., Wilson, J. B., Gravely, M. E., Stevens, P. D., Chen, C. J., Lindeman, J. G., Wong, S. C., Miller, A., Gottleib, M., Huisman, T. H. J. Hb Leslie, an unstable hemoglobin due to deletion of glutamine residue beta 131 (H9) occurring in association with beta-thalassemia, HbC, and HbS. Blood 47: 99-112, 1976. [PubMed: 1244915]

  680. Maekawa, M., Maekawa, T., Fujiwara, N., Tabara, K., Matsuda, G. Hemoglobin Nagasaki (beta 17 glu): a new abnormal human hemoglobin found in one family in Nagasaki. Int. J. Protein Res. 2: 147-156, 1970. [PubMed: 4950989]

  681. Magenis, R. E., Donlon, T. A., Tomar, D. R. Localization of the beta-globin gene to 11p15 by in situ hybridization: utilization of chromosome 11 rearrangements. Hum. Genet. 69: 300-303, 1985. [PubMed: 3988280] [Full Text: https://doi.org/10.1007/BF00291645]

  682. Makhoul, N. J., Wells, R. S., Kaspar, H., Shbaklo, H., Taher, A., Chakar, N., Zalloua, P. A. Genetic heterogeneity of beta thalassemia in Lebanon reflects historic and recent population migration. Ann. Hum. Genet. 69: 55-66, 2005. [PubMed: 15638828] [Full Text: https://doi.org/10.1046/j.1529-8817.2004.00138.x]

  683. Malcorra-Azpiazu, J. J., Balda-Aguirre, M. I., Diaz-Chico, J. C., Hu, H., Wilson, J. B., Webber, B. B., Kutlar, F., Kutlar, A., Huisman, T. H. J. Hb Las Palmas or beta49 (CD8) ser-to-phe, a mildly unstable hemoglobin variant. Hemoglobin 12: 163-170, 1988. [PubMed: 3384708] [Full Text: https://doi.org/10.3109/03630268808998022]

  684. Malone, J. I., Shah, S. C., Barness, L. A. Hemoglobin South Florida: a genetic variant with laboratory recognition of only 20% of its product. Am. J. Med. Genet. Suppl. 3: 227-231, 1987.

  685. Manca, L., Cocco, E., Cossu, G., Masala, B. Identification of Hb Hamilton or beta-11(A8)val-to-ile gene by the polymerase chain reaction amplification technique. Biochim. Biophys. Acta 1139: 17-19, 1992. [PubMed: 1610915] [Full Text: https://doi.org/10.1016/0925-4439(92)90076-y]

  686. Manca, L., Formato, M., Masala, B., Gallisai, D., Orzalesi, M. Hemoglobin Hamilton (beta11 (A8) val-to-ile) in Sardinia. Hemoglobin 11: 161-167, 1987. [PubMed: 3623977] [Full Text: https://doi.org/10.3109/03630268709005792]

  687. Maniatis, A., Bousios, T., Nagel, R. L., Balazs, T., Ueda, Y., Bookchin, R. M., Maniatis, G. M. Hemoglobin Crete (beta 129 ala-to-pro): a new high-affinity variant interacting with beta-zero and delta-beta-zero-thalassemia. Blood 54: 54-62, 1979. [PubMed: 36184]

  688. Maniatis, T., Fritsch, E. F., Lauer, J., Lawn, R. M. The molecular genetics of human hemoglobins. Annu. Rev. Genet. 14: 145-178, 1980. [PubMed: 6452087] [Full Text: https://doi.org/10.1146/annurev.ge.14.120180.001045]

  689. Mant, M. J., Salkie, M. L., Cope, N., Appling, F., Bolch, K., Jayal-Akshmi, M., Gravely, M., Wilson, J. B., Huisman, T. H. J. Hb Alberta or beta 101 (G3) glu-to-gly, a new high-oxygen-affinity hemoglobin variant causing erythrocytosis. Hemoglobin 1: 183-194, 1977. [PubMed: 1052180] [Full Text: https://doi.org/10.3109/03630267608991679]

  690. Maquat, L. E., Kinniburgh, A. J., Beach, L. R., Honig, G. R., Lazerson, J., Ershler, W. B., Ross, J. Processing of human beta-globin mRNA precursor to mRNA is defective in three patients with B+-thalassemia. Proc. Nat. Acad. Sci. 77: 4287-4291, 1980. [PubMed: 6933479] [Full Text: https://doi.org/10.1073/pnas.77.7.4287]

  691. Maragoudaki, E., Kanavakis, E., Traeger-Synodinos, J., Vrettou, C., Tzetis, M., Metaxotou-Mavrommati, A., Kattamis, C. Molecular, haematological and clinical studies of the -101 C-to-T substitution of the beta-globin gene promoter in 25 beta-thalassaemia intermedia patients and 45 heterozygotes. Brit. J. Haemat. 107: 699-706, 1999. [PubMed: 10606872] [Full Text: https://doi.org/10.1046/j.1365-2141.1999.01788.x]

  692. Marengo-Rowe, A. J., Lorkin, P. A., Gallo, E., Lehmann, H. Haemoglobin Dhofar--a new variant from southern Arabia. Biochim. Biophys. Acta 168: 58-63, 1968. [PubMed: 5684629] [Full Text: https://doi.org/10.1016/0005-2795(68)90233-x]

  693. Marinucci, M., Boissel, J. P., Massa, A., Wajcman, H., Tentori, L., Labie, D. Hemoglobin Maputo: a new beta-chain variant (beta 47 (CD6) asp-to-tyr) in combination with hemoglobin S, identified by high performance liquid chromatography (HPLC). Hemoglobin 7: 423-433, 1983. [PubMed: 6629824] [Full Text: https://doi.org/10.3109/03630268309038411]

  694. Marinucci, M., Giuliani, A., Maffi, D., Massa, A., Giampaolo, A., Mavilio, F., Zannotti, M., Tentori, L. Hemoglobin Bologna (beta61 (E5) lys-to-met) an abnormal human hemoglobin with low oxygen affinity. Biochim. Biophys. Acta 668: 209-215, 1981. [PubMed: 7225407] [Full Text: https://doi.org/10.1016/0005-2795(81)90028-3]

  695. Marinucci, M., Mavilio, F., Fontanarosa, P. P., Tentori, L., Brancati, C. Studies on a family with Hb J (Calabria) (beta 64 (E8) gly-to-asp). Hemoglobin 3: 327-340, 1979. [PubMed: 500375] [Full Text: https://doi.org/10.3109/03630267908997538]

  696. Marinucci, M., Mavilio, F., Tentori, L., Alberti, R. Hemoglobin Gavello (beta 47(CD6) asp-to-gly): a new hemoglobin variant from Polesine (Italy). Hemoglobin 1: 771-779, 1977. [PubMed: 604315] [Full Text: https://doi.org/10.3109/03630267709003906]

  697. Marti, H. R., Winterhalter, K. H., di Iorio, E. E., Lorkin, P. A., Lehmann, H. Hb Altdorf (beta 135 (H13) ala-to-pro): a new electrophoretically silent unstable haemoglobin variant from Switzerland. FEBS Lett. 63: 193-196, 1976. [PubMed: 1261680] [Full Text: https://doi.org/10.1016/0014-5793(76)80224-4]

  698. Martin, H., Heupke, G., Pfleiderer, G., Woerner, W. Haemoglobin D in a Frankfurt family. Folia Haemat. 4: 233-241, 1960. [PubMed: 14421678]

  699. Martinez, G., Canizares, M. E. A second family with hemoglobin Willamette. Hemoglobin 8: 193-195, 1984. [PubMed: 6590550] [Full Text: https://doi.org/10.3109/03630268408991713]

  700. Martinez, G., Colombo, B. Interaction between Hb S and Hb Hope in a Cuban family. Hemoglobin 8: 519-522, 1984. [PubMed: 6500990] [Full Text: https://doi.org/10.3109/03630268408991737]

  701. Martinez, G., Lima, F., Colombo, B. Haemoglobin J Guantanamo (beta 128 (H6) ala replaced by asp): a new fast unstable haemoglobin found in a Cuban family. Biochim. Biophys. Acta 491: 1-6, 1977. [PubMed: 849451] [Full Text: https://doi.org/10.1016/0005-2795(77)90034-4]

  702. Martino, T., Kaplan, F., Diamond, S., Oppenheim, A., Scriver, C. R. Probable identity by descent and discovery of familial relationships by means of a rare beta-thalassemia haplotype. Hum. Mutat. 9: 86-87, 1997. [PubMed: 8990020] [Full Text: https://doi.org/10.1002/(SICI)1098-1004(1997)9:1<86::AID-HUMU20>3.0.CO;2-K]

  703. Matsuno, Y., Yamashiro, Y., Yamamoto, K., Hattori, Y., Yamamoto, K., Ohba, Y., Miyaji, T. A possible example of gene conversion with a common beta-thalassemia mutation and chi sequence present in the beta-globin gene. Hum. Genet. 88: 357-358, 1992. [PubMed: 1733840] [Full Text: https://doi.org/10.1007/BF00197277]

  704. McCurdy, P. R., Fox, J., Moo-Penn, W. Apparent duplication of the beta-chain gene in man. (Abstract) Am. J. Hum. Genet. 27: 62A, 1975.

  705. McKusick, V. A. Human Genetics. Englewood Cliffs, N. J.: Prentice-Hall (pub.) 1969.

  706. Mears, J. G., Lachman, H. M., Cabannes, R., Amegnizin, K. P. E., Labie, D., Nagel, R. L. Sickle gene: its origin and diffusion from West Africa. J. Clin. Invest. 68: 606-610, 1981. [PubMed: 6268660] [Full Text: https://doi.org/10.1172/jci110294]

  707. Merault, G., Keclard, L., Garin, J., Poyart, C., Blouquit, Y., Arous, N., Galacteros, F., Feingold, J., Rosa, J. Hemoglobin La Desirade, beta129 (H7) ala-to-val: a new unstable hemoglobin. Hemoglobin 10: 593-605, 1986. [PubMed: 3557994] [Full Text: https://doi.org/10.3109/03630268609036564]

  708. Merault, G., Keclard, L., Saint-Martin, C., Jasmin, K., Campier, A., Delanoe-Garin, J., Arous, N., Fortune, R., Theodore, M., Seytor, S., Rosa, J., Blouquit, Y., Galacteros, F. Hemoglobin Roseau-Pointe a Pitre, beta90 (F6) glu-to-gly: a new variant with slight instability and low oxygen affinity. FEBS Lett. 184: 10-13, 1985. [PubMed: 3838727] [Full Text: https://doi.org/10.1016/0014-5793(85)80642-6]

  709. Merghoub, T., Sanchez-Mazas, A., Tamouza, R., Lu, C. Y., Bouzid, K., Ardjoun, F. Z., Labie, D., Lapoumeroulie, C., Elion, J. Haemoglobin D-Ouled Rabah among the Mozabites: a relevant variant to trace the origin of Berber-speaking populations. Europ. J. Hum. Genet. 5: 390-396, 1997. [PubMed: 9450184]

  710. Metherall, J. E., Collins, F. S., Pan, J., Weissman, S. M., Forget, B. G. Beta-0-thalassemia caused by a base substitution that creates an alternative splice acceptor site in an intron. EMBO J. 5: 2551-2557, 1986. [PubMed: 3780671] [Full Text: https://doi.org/10.1002/j.1460-2075.1986.tb04534.x]

  711. Millar, C. M., Phelan, L., Bain, B. J. Diabetes mellitus diagnosed following request for haemoglobin electrophoresis. Brit. J. Haemat. 117: 778 only, 2002. [PubMed: 12060111] [Full Text: https://doi.org/10.1046/j.1365-2141.2002.03556.x]

  712. Miller, D. R., Smetanina, N. S., Gu, L.-H., Leonova, J. Y., Huisman, T. H. J. Hb Sogn or alpha-2-beta-2-14(All)leu-to-arg in combination with an alpha-thalassemia heterozygosity. Hemoglobin 20: 131-134, 1996. [PubMed: 8811316] [Full Text: https://doi.org/10.3109/03630269609027918]

  713. Miller, D. R., Weed, R. I., Stamatoyannopoulos, G., Yoshida, A. Hemoglobin Koln disease occurring as a fresh mutation: erythrocyte metabolism and survival. Blood 38: 715-729, 1971. [PubMed: 4942314]

  714. Miller, D. R., Wilson, J. B., Kutlar, A., Huisman, T. H. J. Hb Bicetre or beta63(E7)his-to-pro in a white male: clinical observations over a period of 25 years. Am. J. Hemat. 21: 209-214, 1986. [PubMed: 3753631] [Full Text: https://doi.org/10.1002/ajh.2830210210]

  715. Miller, H. I., Konkel, D. A., Leder, P. An intervening sequence of the mouse beta-globin major gene shares extensive homology only with beta-globin genes. Nature 275: 772-776, 1978. [PubMed: 568218] [Full Text: https://doi.org/10.1038/275772a0]

  716. Milner, P. F., Corley, C. C., Pomeroy, W. L., Wilson, J. B., Gravely, M., Huisman, T. H. J. Thalassemia intermedia caused by heterozygosity for both beta-thalassemia and hemoglobin Saki (beta 14(A11) leu-to-pro). Am. J. Hemat. 1: 283-292, 1976. [PubMed: 998617] [Full Text: https://doi.org/10.1002/ajh.2830010302]

  717. Milner, P. F., Miller, C., Grey, R., Seakins, M., De Jong, W. W., Went, L. N. Hemoglobin O Arab: interaction with hemoglobin S and hemoglobin C. New Eng. J. Med. 283: 1417-1424, 1970. [PubMed: 5481775] [Full Text: https://doi.org/10.1056/NEJM197012242832601]

  718. Milner, P. F. High incidence of hemoglobin G (Accra) in a rural district in Jamaica. J. Med. Genet. 4: 88-90, 1967. [PubMed: 5619995] [Full Text: https://doi.org/10.1136/jmg.4.2.88]

  719. Minnich, V., Hill, R. J., Khuri, P. D., Anderson, M. E. Hemoglobin Hope: a beta chain variant. Blood 25: 830-838, 1965. [PubMed: 14282052]

  720. Miranda, S. R. P., Kimura, E. M., Saad, S. T. O., Costa, F. F. Identification of Hb Zurich (beta-63 (E7) his-to-arg) by DNA analysis in a Brazilian family. Hemoglobin 18: 337-341, 1994. [PubMed: 7852089] [Full Text: https://doi.org/10.3109/03630269408996200]

  721. Miranda, S. R. P., Kimura, E. M., Teixeira, R. C., Bertuzzo, C. S., Ramalho, A. S., Saad, S. T. O., Costa, F. F. Hb Camperdown [alpha-2-beta-2-104(G6)arg-to-ser] identified by DNA analysis in a Brazilian family. Hemoglobin 20: 147-153, 1996. [PubMed: 8811319] [Full Text: https://doi.org/10.3109/03630269609027921]

  722. Miyaji, T., Ohba, Y., Matsuoka, M., Kudoh, H., Asano, M., Yamamoto, K., Satoh, T. Hemoglobin Karatsu: beta-120 (GH3) lysine-to-asparagine: an example of Hb Riyadh in Japan. Hemoglobin 1: 461-466, 1977. [PubMed: 893141] [Full Text: https://doi.org/10.3109/03630267709027863]

  723. Miyaji, T., Ohba, Y., Yamamoto, K., Shibata, S., Iuchi, I., Hamilton, H. B. Hemoglobin Hijiyama: a new fast-moving hemoglobin in a Japanese family. Science 159: 204-206, 1968. [PubMed: 5634912] [Full Text: https://doi.org/10.1126/science.159.3811.204]

  724. Miyaji, T., Ohba, Y., Yamamoto, K., Shibata, S., Iuchi, I., Takenaka, M. Japanese haemoglobin variant. Nature 217: 89-90, 1968. [PubMed: 5635645] [Full Text: https://doi.org/10.1038/217089a0]

  725. Miyaji, T., Suzuki, H., Ohba, Y., Shibata, S. Hemoglobin Agenogi (alpha-2 beta-2 90 lys), a slow-moving hemoglobin of a Japanese family resembling hemoglobin E. Clin. Chim. Acta 14: 624-629, 1966. [PubMed: 5972415] [Full Text: https://doi.org/10.1016/0009-8981(66)90187-2]

  726. Miyazaki, A., Nakanishi, T., Kishikawa, M., Nakagawa, T., Shimizu, A., Mawjood, A. H. M., Imai, K., Aoki, Y., Kikuchi, M. Compound heterozygosity for beta(+)-thalassemia (-31(A-to-G)) and a new variant with low oxygen affinity, Hb Sagami (beta-139(H17)asn-to-thr). Hemoglobin 23: 267-271, 1999. [PubMed: 10490140] [Full Text: https://doi.org/10.3109/03630269909005708]

  727. Miyazaki, A., Nakanishi, T., Shimizu, A., Mizobuchi, M., Yamada, Y., Imai, K. Hb Kochi (beta-141(H19)leu-to-val (g.1404C-G); 144-146(HC1-3)lys-tyr-his-0 (g.1413A-T)): a new variant with increased oxygen affinity. Hemoglobin 29: 1-10, 2005. [PubMed: 15768550]

  728. Miyazaki, A., Nakanishi, T., Shimizu, A., Ninomiya, K., Nishimura, S., Imai, K. Hb Buzen [beta-138(H16)ala-to-thr (g.1395G-A)]: a new beta chain variant. Hemoglobin 27: 243-247, 2003. [PubMed: 14649315] [Full Text: https://doi.org/10.1081/hem-120026049]

  729. Modell, B., Darlison, M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull. World Health Organ. 86: 480-487, 2008. [PubMed: 18568278] [Full Text: https://doi.org/10.2471/blt.06.036673]

  730. Modiano, D., Bancone, G., Ciminelli, B. M., Pompei, F., Blot, I., Simpore, J., Modiano, G. Haemoglobin S and haemoglobin C: 'quick but costly' versus 'slow but gratis' genetic adaptations to Plasmodium falciparum malaria. Hum. Molec. Genet. 17: 789-799, 2008. Note: Erratum: Hum. Molec. Genet. 17: 2070 only, 2008. [PubMed: 18048408] [Full Text: https://doi.org/10.1093/hmg/ddm350]

  731. Modiano, D., Luoni, G., Sirima, B. S., Simpore, J., Verra, F., Konate, A., Rastrelli, E., Olivieri, A., Calissano, C., Paganotti, G. M., D'Urbano, L., Sanou, I., Sawadogo, A., Modiano, G., Coluzzi, M. Haemoglobin C protects against clinical Plasmodium falciparum malaria. Nature 414: 305-308, 2001. [PubMed: 11713529] [Full Text: https://doi.org/10.1038/35104556]

  732. Moghimi, B., Yavarian, M., Oberkanins, C., Amini, S. S. H., Khatami, S., Rouhi, S., Kahrizi, K., Najmabadi, H. Hb Dhonburi (Neapolis) (beta-126(H4)val-to-gly) identified in a family from northern Iran. Hemoglobin 28: 353-356, 2004. [PubMed: 15658193] [Full Text: https://doi.org/10.1081/hem-200038876]

  733. Moi, P., Faa, V., Marini, M. G., Asunis, I., Ibba, G., Cao, A., Rosatelli, M. C. A novel silent beta-thalassemia mutation in the distal CACCC box affects the binding and responsiveness to EKLF. Brit. J. Haemat. 126: 881-884, 2004. [PubMed: 15352994] [Full Text: https://doi.org/10.1111/j.1365-2141.2004.05146.x]

  734. Mojzikova, R., Dolezel, P., Pavlicek, J., Mlejnek, P., Pospisilova, D., Divoky, V. Partial glutathione reductase deficiency as a cause of diverse clinical manifestations in a family with unstable hemoglobin (hemoglobin Hana, beta-63(E7) his-asn). Blood Cells Mol. Dis. 45: 219-222, 2010. [PubMed: 20692194] [Full Text: https://doi.org/10.1016/j.bcmd.2010.07.003]

  735. Molchanova, T. P., Postnikov, Y. V., Gu, L.-H., Huisman, T. H. J. The beta-thalassemia allele in the noble Russian family Lermontov is identified as the ATG-to-ACG change in the initiation codon. Hemoglobin 22: 283-286, 1998. [PubMed: 9629504] [Full Text: https://doi.org/10.3109/03630269809113143]

  736. Molchanova, T. P., Postnikov, Y. V., Gu, L.-H., Prior, J. F., Raven, J. L., Bennett, J. A., Huisman, T. H. J. Hb Tigraye or beta79 (EF3) asp-to-his (GAC-to-CAC): a hemoglobin variant with increased oxygen affinity observed in an Ethiopian male. Hemoglobin 17: 247-250, 1993. [PubMed: 8330977] [Full Text: https://doi.org/10.3109/03630269308998899]

  737. Molchanova, T. P., Postnikov, Y. V., Pobedimskaya, D. D., Smetanina, N. S., Moschan, A. A., Kazanetz, E. G., Tokarev, Y. N., Huisman, T. H. J. Hb Alesha or beta67 (E11) val-to-met: a new unstable hemoglobin variant identified through sequencing of amplified DNA. Hemoglobin 17: 217-225, 1993. [PubMed: 8330974] [Full Text: https://doi.org/10.3109/03630269308998896]

  738. Molchanova, T. P., Wilson, J. B., Gu, L.-H., Guemira, F., Fattoum, S., Huisman, T. H. J. Hb Bab-Saadoun or beta48 (CD7) leu-to-pro, a mildly unstable variant found in an Arabian boy from Tunisia. Hemoglobin 16: 267-273, 1992. [PubMed: 1517103] [Full Text: https://doi.org/10.3109/03630269208998867]

  739. Monn, E., Gaffney, P. J., Lehmann, H. Haemoglobin Sogn (beta 14 arginine)--a new hemoglobin variant. Scand. J. Haemat. 5: 353-360, 1968. [PubMed: 5710451]

  740. Monplaisir, N., Merault, G., Poyart, C., Rhoda, M.-D., Craescu, C., Vidaud, M., Galacteros, F., Blouquit, Y., Rosa, J. Hemoglobin S Antilles: a variant with lower solubility than hemoglobin S and producing sickle cell disease in heterozygotes. Proc. Nat. Acad. Sci. 83: 9363-9367, 1986. [PubMed: 3467311] [Full Text: https://doi.org/10.1073/pnas.83.24.9363]

  741. Moo-Penn, W. F., Bechtel, K. C., Johnson, M. H., Jue, D. L., Therrell, B. L., Jr., Morrison, B. Y., Schmidt, R. M. Hemoglobin Fannin-Lubbock (beta 119 (GH2) gly-to-asp): a new hemoglobin variant at the alpha-1-beta-1-contact. Biochim. Biophys. Acta 453: 472-477, 1976. [PubMed: 11828] [Full Text: https://doi.org/10.1016/0005-2795(76)90142-2]

  742. Moo-Penn, W. F., Bechtel, K. C., Schmidt, R. M., Johnson, M. H., Jue, D. L., Schmidt, D. E., Jr., Dunlap, W. M., Opella, S. J., Bonaventura, J., Bonaventura, C. Hemoglobin Raleigh (beta 1 valine-to-acetylalanine): structural and functional characterization. Biochemistry 16: 4872-4879, 1977. [PubMed: 20942] [Full Text: https://doi.org/10.1021/bi00641a019]

  743. Moo-Penn, W. F., Hine, T. K., Johnson, M. H., Jue, D. L., Holland, S., George, S., Pierce, A. M., Michalski, L. A., McDonald, M. J. Hb Rancho Mirage [beta143(H21)his-to-asp]; a variant in the 2,3-DPG binding site showing normal oxygen affinity at physiological pH. Hemoglobin 16: 35-44, 1992. [PubMed: 1634360] [Full Text: https://doi.org/10.3109/03630269209005674]

  744. Moo-Penn, W. F., Johnson, M. H., Bechtel, K. C., Jue, D. L., Therrell, B. L., Jr., Schmidt, R. M. Hemoglobins Austin and Waco: two hemoglobins with substitutions in the alpha-1-beta-2 contact region. Arch. Biochem. Biophys. 179: 86-94, 1977. [PubMed: 14597] [Full Text: https://doi.org/10.1016/0003-9861(77)90089-3]

  745. Moo-Penn, W. F., Johnson, M. H., Jue, D. L., Lonser, R. Hb Hinsdale (beta139(H17)asn-to-lys): a variant in the central cavity showing reduced affinity for oxygen and 2,3-diphosphoglycerate. Hemoglobin 13: 455-464, 1989. [PubMed: 2513289] [Full Text: https://doi.org/10.3109/03630268908998084]

  746. Moo-Penn, W. F., Johnson, M. H., McGuffey, J. E., Jue, D. L., Therrell, B. L., Jr. Hemoglobin Rio Grande (beta8 (A5) lys-to-thr): a new variant found in a Mexican-American family. Hemoglobin 7: 91-95, 1983. [PubMed: 6857757] [Full Text: https://doi.org/10.3109/03630268309038405]

  747. Moo-Penn, W. F., Johnson, M. H., McGuffey, J. E., Jue, D. L. Hemoglobin Shelby [beta131 (H9) gln-to-lys]: a correction to the structure of hemoglobin Deaconess and hemoglobin Leslie. Hemoglobin 8: 583-593, 1984. [PubMed: 6526653] [Full Text: https://doi.org/10.3109/03630268408991743]

  748. Moo-Penn, W. F., Jue, D. L., Bechtel, K. C., Johnson, M. H., Bemis, E., Brosious, E., Schmidt, R. M. Hemoglobin Deaconess, a new deletion mutant: beta131 (H9) glutamine deleted. Biochem. Biophys. Res. Commun. 65: 8-15, 1975. [PubMed: 1148000] [Full Text: https://doi.org/10.1016/s0006-291x(75)80054-4]

  749. Moo-Penn, W. F., Jue, D. L., Bechtel, K. C., Johnson, M. H., Schmidt, R. M. Hemoglobin Providence: a human hemoglobin variant occurring in two forms in vivo. J. Biol. Chem. 251: 7557-7562, 1976. [PubMed: 1002699]

  750. Moo-Penn, W. F., Jue, D. L., Johnson, M. H., Bechtel, K. C., Patchen, L. C. Hemoglobin variants and methods used for their characterization during 7 years of screening at the Center for Disease Control. Hemoglobin 4: 347-361, 1980. [PubMed: 6252122] [Full Text: https://doi.org/10.3109/03630268008996216]

  751. Moo-Penn, W. F., Jue, D. L., Johnson, M. H., Olsen, K. W., Shih, D., Jones, R. T., Lux, S. E., Rodgers, P., Arnone, A. Hemoglobin Brockton (beta138 (H16) ala-to-pro): an unstable variant near the C-terminus of the beta-subunits with normal oxygen-binding properties. Biochemistry 27: 7614-7619, 1988. [PubMed: 3207692] [Full Text: https://doi.org/10.1021/bi00420a007]

  752. Moo-Penn, W. F., McGuffey, J. E., Jue, D. L., Johnson, M. H., Schum, T. Hemoglobin New Mexico: beta100 (G2) pro-to-arg: a variant hemoglobin associated with erythrocytosis (BBA 32356). Biochim. Biophys. Acta 832: 192-196, 1985. [PubMed: 3840697] [Full Text: https://doi.org/10.1016/0167-4838(85)90331-0]

  753. Moo-Penn, W. F., Schmidt, R. M., Jue, D. L., Bechtel, K. C., Wright, J. M., Horne, M. K., III, Haycraft, G. L., Roth, E. F., Nagel, R. L. Hemoglobin S Travis: a sickling hemoglobin with two amino acid substitutions (beta6 glutamic acid to valine and beta142 alanine to valine). Europ. J. Biochem. 77: 561-566, 1977. [PubMed: 19257] [Full Text: https://doi.org/10.1111/j.1432-1033.1977.tb11699.x]

  754. Moo-Penn, W. F., Schneider, R. G., Andrian, S., Das, D. K. Hemoglobin Detroit: beta 95 (FG2) lysine-to-asparagine. Biochim. Biophys. Acta 536: 283-288, 1978. [PubMed: 708768] [Full Text: https://doi.org/10.1016/0005-2795(78)90075-2]

  755. Moo-Penn, W. F., Schneider, R. G., Shih, T., Jones, R. T., Govindarajan, S., Govindarajan, P. G., Patchen, L. C. Hemoglobin Ohio (beta 142 ala-to-asp): a new abnormal hemoglobin with high oxygen affinity and erythrocytosis. Blood 56: 246-250, 1980. [PubMed: 7397380]

  756. Moo-Penn, W. F., Wolff, J. A., Simon, G., Vacek, M., Jue, D. L., Johnson, M. H. Hemoglobin Presbyterian: beta 108(G10) asn-to-lys. A haemoglobin variant with low oxygen affinity. FEBS Lett. 92: 53-56, 1978. [PubMed: 668922] [Full Text: https://doi.org/10.1016/0014-5793(78)80720-0]

  757. Moo-Penn, W. F. Personal Communication. Atlanta, Ga. 1981.

  758. Moon, A. M., Ley, T. J. Conservation of the primary structure, organization, and function of the human and mouse beta-globin locus-activating regions. Proc. Nat. Acad. Sci. 87: 7693-7697, 1990. [PubMed: 2217202] [Full Text: https://doi.org/10.1073/pnas.87.19.7693]

  759. Morton, C. C., Kirsch, I. R., Taub, R., Orkin, S. H., Brown, J. A. Localization of the beta-globin gene by chromosomal in situ hybridization. Am. J. Hum. Genet. 36: 576-585, 1984. [PubMed: 6587773]

  760. Mrad, A., Blouquit, Y., Lacombe, C., Blibech, R., Arous, N., Bardakdjian, J., Kastally, R., Rosa, J., Galacteros, F. Hb Tunis: (beta124 (H2) pro-to-ser), a new beta-chain variant identified by HPLC. Hemoglobin 12: 23-30, 1988. [PubMed: 3384695] [Full Text: https://doi.org/10.3109/03630268808996879]

  761. Muller, C. J., Kingma, S. Haemoglobin Zurich beta 63 arg. Biochim. Biophys. Acta 50: 595, 1961. [PubMed: 13726693] [Full Text: https://doi.org/10.1016/0006-3002(61)90028-2]

  762. Murawski, K., Carta, S., Sorcini, M., Tentori, L., Vivaldi, G., Antonini, E., Brunori, M., Wyman, J., Bucci, E., Rossi-Fanelli, A. Observations on the structure and behavior of hemoglobin M (Radom). Arch. Biochem. 111: 197-201, 1965. [PubMed: 5851873] [Full Text: https://doi.org/10.1016/0003-9861(65)90340-1]

  763. Murru, S., Loudianos, G., Deiana, M., Camaschella, C., Sciarratta, G. V., Agosti, S., Parodi, M. I., Cerruti, P., Cao, A., Pirastu, M. Molecular characterization of beta-thalassemia intermedia in patients of Italian descent and identification of three novel beta-thalassemia mutations. Blood 77: 1342-1347, 1991. [PubMed: 2001456]

  764. Murru, S., Pischedda, M. C., Cao, A., Rosatelli, M. C., Pirastu, M., Sciarratta, G. V. A promoter mutation of the beta-globin gene (-101 C-to-T) has an age-related expression pattern. (Letter) Blood 81: 2818-2819, 1993. [PubMed: 7683931]

  765. Murru, S., Poddie, D., Sciarratta, G. V., Agosti, S., Baffico, M., Melevendi, C., Pirastu, M., Cao, A. A novel beta-globin structural mutant, Hb Brescia (beta114 leu-to-pro), causing a severe beta-thalassemia intermedia phenotype. Hum. Mutat. 1: 124-128, 1992. [PubMed: 1301199] [Full Text: https://doi.org/10.1002/humu.1380010207]

  766. Musumeci, S., Schiliro, G., Fisher, A., Musco, A., Marinucci, M., Mavilio, F., Fontanarosa, P. P., Tentori, L. Hb J Baltimore (beta 16 (A13) gly-to-asp) in association with beta-thalassemia in a Sicilian family. Hemoglobin 3: 459-464, 1979. [PubMed: 511585] [Full Text: https://doi.org/10.3109/03630267909002282]

  767. Nagel, R. L., Daar, S., Romero, J. R., Suzuka, S. M., Gravell, D., Bouhassira, E., Schwartz, R. S., Fabry, M. E., Krishnamoorthy, R. Hb S-Oman heterozygote: a new dominant sickle syndrome. Blood 92: 4375-4382, 1998. [PubMed: 9834244]

  768. Nagel, R. L., Fabry, M. E., Pagnier, J., Zohoun, I., Wajcman, H., Baudin, V., Labie, D. Hematologically and genetically distinct forms of sickle cell anemia in Africa: the Senegal type and the Benin type. New Eng. J. Med. 312: 880-884, 1985. [PubMed: 2579336] [Full Text: https://doi.org/10.1056/NEJM198504043121403]

  769. Nagel, R. L., Lin, M. J., Witkowska, H. E., Fabry, M. E., Bestak, M., Hirsch, R. E. Compound heterozygosity for hemoglobin C and Korle-Bu: moderate microcytic hemolytic anemia and acceleration of crystal formation. Blood 82: 1907-1912, 1993. Note: Erratum: Blood 83: 3105 only, 1994. [PubMed: 7691242]

  770. Nagel, R. L., Lynfield, J., Johnson, J., Landau, L., Bookchin, R. M., Harris, M. B. Hemoglobin Beth Israel: a mutant causing clinically apparent cyanosis. New Eng. J. Med. 295: 125-130, 1976. [PubMed: 1272328] [Full Text: https://doi.org/10.1056/NEJM197607152950302]

  771. Nakamura, T., Araki, M., Kuzuo, Y., Harano, T., Harano, K., Ohba, Y. Hb Nagasaki [beta-17(A14)lys-to-glu]: a second case found in a Japanese family. Hemoglobin 21: 187-188, 1997. [PubMed: 9101287] [Full Text: https://doi.org/10.3109/03630269708997522]

  772. Nakanishi, T., Miyazaki, A., Kishikawa, M., Shimizu, A., Aoki, Y., Kikuchi, M. Hb Peterborough [beta-111(G13)val-to-phe] in Japan: rapid identification by ESI/MS using proteolytic digests of oxidized globin. Hemoglobin 22: 23-35, 1998. [PubMed: 9494045] [Full Text: https://doi.org/10.3109/03630269809071514]

  773. Nakanishi, T., Miyazaki, A., Kishikawa, M., Shimizu, A., Kishida, O., Sumi, S., Tsubakio, T., Imai, K. A new hemoglobin variant found during Hb A(1c) measurement: Hb Hokusetsu [beta-52(D3)asp-to-gly]. Hemoglobin 22: 355-371, 1998. [PubMed: 9730366] [Full Text: https://doi.org/10.3109/03630269809071530]

  774. Nakatsuji, T., Miwa, S., Ohba, Y., Hattori, Y., Miyaji, T., Hino, S., Matsumoto, N. A new unstable hemoglobin, Hb Yokohama (beta31 (B13) leu-to-pro), causing hemolytic anemia. Hemoglobin 5: 667-678, 1981. [PubMed: 7338469] [Full Text: https://doi.org/10.3109/03630268108991834]

  775. Nakatsuji, T., Miwa, S., Ohba, Y., Hattori, Y., Miyaji, T., Miyata, H., Shinohara, T., Hori, T., Takayama, J. Hemoglobin Miyashiro (beta23 (B5) val-to-gly): an electrophoretically silent variant discovered by the isopropanol test. Hemoglobin 5: 653-666, 1981. [PubMed: 7338468] [Full Text: https://doi.org/10.3109/03630268108991833]

  776. Naritomi, Y., Naito, Y., Nakashima, H., Yokota, E., Imamura, T. A substitution of cytosine for thymine in codon 110 of the human beta-globin gene is a novel cause of beta-thalassemia phenotypes. Hum. Genet. 80: 11-15, 1988. [PubMed: 3417300] [Full Text: https://doi.org/10.1007/BF00451448]

  777. Navas, P. A., Li, Q., Peterson, K. R., Swank, R. A., Rohde, A., Roy, J., Stamatoyannopoulos, G. Activation of the beta-like globin genes in transgenic mice is dependent on the presence of the beta-locus control region. Hum. Molec. Genet. 11: 893-903, 2002. [PubMed: 11971871] [Full Text: https://doi.org/10.1093/hmg/11.8.893]

  778. Navas, P. A., Swank, R. A., Yu, M., Peterson, K. R., Stamatoyannopoulos, G. Mutation of a transcriptional motif of a distant regulatory element reduces the expression of embryonic and fetal globin genes. Hum. Molec. Genet. 12: 2941-2948, 2003. [PubMed: 14506128] [Full Text: https://doi.org/10.1093/hmg/ddg319]

  779. Necheles, T. F., Allen, D. M., Gerald, P. S. The many forms of thalassemia: definition and classification of the thalassemia syndromes. Ann. N.Y. Acad. Sci. 165: 5-12, 1969. [PubMed: 5260168] [Full Text: https://doi.org/10.1111/j.1749-6632.1969.tb27771.x]

  780. Neel, J. V., Kaplan, E., Zuelzer, W. W. Further studies of hemoglobin C. I. A description of three additional families segregating for hemoglobin C and sickle cell hemoglobin. Blood 8: 724-734, 1953. [PubMed: 13066514]

  781. Neel, J. V. The inheritance of sickle cell anemia. Science 110: 64-66, 1949. [PubMed: 17774955] [Full Text: https://doi.org/10.1126/science.110.2846.64]

  782. Negri Arjona, S., Eloy-Garcia, J. M., Gu, L.-H., Smetanina, N. S., Huisman, T. H. J. The dominant beta-thalassaemia in a Spanish family is due to a frameshift that introduces an extra CGG codon (=arginine) at the 5-prime end of the second exon. Brit. J. Haemat. 93: 841-844, 1996. [PubMed: 8703815] [Full Text: https://doi.org/10.1046/j.1365-2141.1996.d01-1725.x]

  783. Negri Arjona, S., Maldonado Eloy-Garcia, J., Molchanova, T. P., Wilson, J. B., Gu, L.-H., Huisman, T. H. J. Hb Brockton (beta-138 (H16) ala-to-pro) observed in a Spanish girl. Hemoglobin 16: 511-514, 1992. [PubMed: 1487422] [Full Text: https://doi.org/10.3109/03630269208993119]

  784. Ngiwsara, L., Srisomsap, C., Winichagoon, P., Fucharoen, S., Svasti, J. Hb Kodaira II [beta-146(HC3)his-to-gln] detected in Thailand. Hemoglobin 27: 37-39, 2003. [PubMed: 12603092] [Full Text: https://doi.org/10.1081/hem-120018434]

  785. Niazi, G. A., Zamanianpoor, M., Ala, F. Hemoglobin G Saskatoon in association with PNH in an Iranian soldier. Hemoglobin 5: 85-87, 1981. [PubMed: 7204096] [Full Text: https://doi.org/10.3109/03630268108996912]

  786. Noguera, N. I., Cardozo, M. A., Gonzalez, F. A., Benavente, C., Milani, A. C., Villegas, A. Hb Agenogi [beta-90(F6)glu-to-lys] in an Argentinean girl. Hemoglobin 26: 201-203, 2002. [PubMed: 12144066] [Full Text: https://doi.org/10.1081/hem-120005461]

  787. North, M. L., Duwig, I., Riou, J., Prome, D., Yapo, A. P., Kister, J., Bardakdjian-Michau, J., Cazenave, J. P., Wajcman, H. Hb Tsukumi (beta-117(G19)his-to-tyr) found in a Moroccan woman. Hemoglobin 25: 107-110, 2001. [PubMed: 11300344] [Full Text: https://doi.org/10.1081/hem-100103076]

  788. Novy, M. J., Edwards, M. J., Metcalfe, J. Hemoglobin Yakima. II. High blood oxygen affinity associated with compensatory erythrocytosis and normal hemodynamics. J. Clin. Invest. 46: 1848-1854, 1967. [PubMed: 6061752] [Full Text: https://doi.org/10.1172/JCI105675]

  789. Novy, M. J., Edwards, M. J., Peterson, E. N., Metcalfe, J. Hemoglobin Yakima: oxygen hemoglobin equilibrium and cardiodynamic effects. (Abstract) Clin. Res. 15: 133, 1967.

  790. Nusapan, R., Conant, J. L. Hemoglobin Southampton (Casper) inclusions resembling intracellular parasites. Blood 141: 3126 only, 2023. [PubMed: 37347497] [Full Text: https://doi.org/10.1182/blood.2023020505]

  791. Nute, P. E., Stamatoyannopoulos, G., Hermodson, M. A., Roth, D. Hemoglobinopathic erythrocytosis due to a new electrophoretically silent variant, hemoglobin San Diego (beta 109 (G11) val-to-met). J. Clin. Invest. 53: 320-328, 1974. [PubMed: 4808644] [Full Text: https://doi.org/10.1172/JCI107553]

  792. O'Donnell, A., Premawardhena, A., Arambepola, M., Samaranayake, R., Allen, S. J., Peto, T. E. A., Fisher, C. A., Cook, J., Corran, P. H., Olivieri, N. F., Weatherall, D. J. Interaction of malaria with a common form of severe thalassemia in an Asian population. Proc. Nat. Acad. Sci. 106: 18716-18721, 2009. [PubMed: 19841268] [Full Text: https://doi.org/10.1073/pnas.0910142106]

  793. O'Gorman, P., Lehmann, H., Allsopp, K. M., Sukumaran, P. K. Sickle cell haemoglobin K disease. Brit. Med. J. 2: 1381-1382, 1963. [PubMed: 14063031] [Full Text: https://doi.org/10.1136/bmj.2.5369.1381]

  794. Ockelford, P. A., Liang, A. Y., Wells, R. M., Vissers, M., Brennan, S. O., Williamson, D., Carrell, R. W. Hemoglobin Volga, beta27 (B9) ala-to-asp: functional and clinical correlations of an unstable hemoglobin. Hemoglobin 4: 295-306, 1980. [PubMed: 7419425] [Full Text: https://doi.org/10.3109/03630268008996212]

  795. Oehme, R., Kohne, E., Kleihauer, E., Horst, J. Hb M Milwaukee: direct detection of the beta-globin gene mutation in three generations of an afflicted family. Hum. Genet. 64: 376-379, 1983. [PubMed: 6311728] [Full Text: https://doi.org/10.1007/BF00292370]

  796. Ogata, K., Ito, T., Okazaki, T., Dan, K., Nomura, T., Nozawa, Y., Kajita, A. Hemoglobin Sendagi (beta42 phe-to-val): a new unstable hemoglobin variant having an amino acid substitution at CD1 of the beta-chain. Hemoglobin 10: 469-481, 1986. [PubMed: 3781864] [Full Text: https://doi.org/10.3109/03630268609014132]

  797. Ohashi, J., Naka, I., Patarapotikul, J., Hananantachai, H., Brittenham, G., Looareesuwan, S., Clark, A. G., Tokunaga, K. Extended linkage disequilibrium surrounding the hemoglobin E variant due to malarial selection. Am. J. Hum. Genet. 74: 1198-1208, 2004. [PubMed: 15114532] [Full Text: https://doi.org/10.1086/421330]

  798. Ohba, Y., Ami, M., Imai, K., Komatsu, K., Amatsu, K. Hb Masuda [beta114(G16)leu-to-met, 119(GH2)gly-to-asp], a hemoglobin with two substitutions in the beta chain. Hemoglobin 13: 753-759, 1989. [PubMed: 2634673] [Full Text: https://doi.org/10.3109/03630268908998850]

  799. Ohba, Y., Hasegawa, Y., Amino, H., Miwa, S., Nakatsuji, T., Hattori, Y., Miyaji, T. Hemoglobin Saitama or beta117 (G19) his-to-pro, a new variant causing hemolytic disease. Hemoglobin 7: 47-56, 1983. [PubMed: 6687721] [Full Text: https://doi.org/10.3109/03630268309038400]

  800. Ohba, Y., Hattori, Y., Ami, M., Yagami, H., Miyaji, T., Tani, Y. Hb Cocody [beta21(B3)asp-to-asn] and Hb Yusa [beta21(B3)asp-to-tyr] found in Japan. Hemoglobin 14: 109-114, 1990. [PubMed: 2384310] [Full Text: https://doi.org/10.3109/03630269009002259]

  801. Ohba, Y., Hattori, Y., Fuyuno, K., Takeda, I., Matsuoka, M., Yoshinaka, H., Satoh, T., Miyaji, T. Two further examples of Hb Hirose, beta37 (C3) trp-to-ser. Hemoglobin 7: 191-193, 1983. [PubMed: 6671905]

  802. Ohba, Y., Hattori, Y., Miyaji, T., Takasaki, M., Shirahama, M., Fujisawa, K., Nakatsuji, T., Miwa, S. Purification and properties of hemoglobin Miyashiro. Hemoglobin 8: 515-518, 1984. [PubMed: 6500989] [Full Text: https://doi.org/10.3109/03630268408991736]

  803. Ohba, Y., Hattori, Y., Sakata, S., Yamashiro, Y., Okayama, N., Hirano, T., Nakanishi, T., Miyazaki, A., Shimizu, A. Hb Niigata [beta-1(NA1)val-to-leu]: the fifth variant with retention of the initiator methionine and partial acetylation. Hemoglobin 21: 179-186, 1997. [PubMed: 9101286] [Full Text: https://doi.org/10.3109/03630269708997521]

  804. Ohba, Y., Imai, K., Kumada, I., Ohsawa, A., Miyaji, T. Hb Moriguchi or beta97(FG4)his-to-tyr substitution at the alpha(1)-beta(2) interface. Hemoglobin 13: 367-376, 1989. [PubMed: 2775360] [Full Text: https://doi.org/10.3109/03630268909003399]

  805. Ohba, Y., Imanaka, M., Matsuoka, M., Hattori, Y., Miyaji, T., Funaki, C., Shibata, K., Shimokata, H., Kuzuya, F., Miwa, S. A new unstable, high oxygen affinity hemoglobin: Hb Nagoya or beta97 (FG4) his-to-pro. Hemoglobin 9: 11-24, 1985. [PubMed: 3838976] [Full Text: https://doi.org/10.3109/03630268508996978]

  806. Ohba, Y., Matsuoka, M., Fuyuno, K., Yamamoto, K., Nishijima, S., Miyaji, T. Further studies on hemoglobin Hofu, beta 126 (H4) val-to-glu, with special reference to its stability. Hemoglobin 5: 89-95, 1981. [PubMed: 7204097] [Full Text: https://doi.org/10.3109/03630268108996913]

  807. Ohba, Y., Matsuoka, M., Miyaji, T., Shibuya, T., Sakuragawa, M. Hemoglobin Bristol or beta 67 (E11) val-to-asp in Japan. Hemoglobin 9: 79-85, 1985. [PubMed: 3997544] [Full Text: https://doi.org/10.3109/03630268508996986]

  808. Ohba, Y., Miyaji, T., Hirosaki, T., Matsuoka, M., Koresawa, M., Iuchi, I. Occurrence of hemoglobin G Coushatta in Japan. Hemoglobin 2: 437-441, 1978. [PubMed: 721611] [Full Text: https://doi.org/10.3109/03630267809007077]

  809. Ohba, Y., Miyaji, T., Ihzumi, T., Shibata, A. Hb Bushwick, an unstable hemoglobin with tendency to lose heme. Hemoglobin 9: 517-523, 1985. [PubMed: 3841345] [Full Text: https://doi.org/10.3109/03630268508997031]

  810. Ohba, Y., Miyaji, T., Matsuoka, M., Sugiyama, K., Suzuki, T., Sugiura, T. Hemoglobin Mizuho or beta 68 (E12) leucine-to-proline, a new unstable variant associated with severe hemolytic anemia. Hemoglobin 1: 467-478, 1977. [PubMed: 893142] [Full Text: https://doi.org/10.3109/03630267709027864]

  811. Ohba, Y., Miyaji, T., Matsuoka, M., Ueda, S., Iuchi, I., Shibata, S. Hemoglobin Tokuchi: beta131 glutamine-to-glutamic acid, an example of hemoglobin Camden in Japan. Acta Haemat. Jpn. 38: 1-7, 1975. [PubMed: 1173714]

  812. Ohba, Y., Miyaji, T., Matsuoka, M., Yamaguchi, K., Yonemitsu, H., Ishii, T., Shibata, S. Hemoglobin Chiba: Hb Hammersmith in a Japanese girl. Acta Haemat. Jpn. 38: 53-58, 1975. [PubMed: 1173718]

  813. Ohba, Y., Miyaji, T., Murakami, M., Kadowaki, S., Fujita, T., Oimomi, M., Hatanaka, H., Ishikawa, K., Baba, S., Hitaka, K., Imai, K. Hb Himeji or beta140 (H18) ala-to-asp: a slightly unstable hemoglobin with increased beta-N-terminal glycation. Hemoglobin 10: 109-126, 1986. [PubMed: 3754244] [Full Text: https://doi.org/10.3109/03630268609046438]

  814. Ohba, Y., Miyaji, T., Shibata, S. Identical substitution in Hb Ube-1 and Hb Koln. Nature N.B. 243: 205-207, 1973. [PubMed: 4514958] [Full Text: https://doi.org/10.1038/newbio243205a0]

  815. Ohba, Y., Yamada, H., Takamatsu, S., Imai, K. Hb Tsurumai [beta-82(EF6)lys-to-gln]: a new Hb variant with high oxygen affinity and erythrocytosis. Hemoglobin 20: 141-146, 1996. [PubMed: 8811318] [Full Text: https://doi.org/10.3109/03630269609027920]

  816. Ohta, Y., Yamaoka, K., Sumida, I., Yanase, T. Haemoglobin Miyada, a beta-delta fusion peptide (anti-Lepore) type discovered in a Japanese family. Nature N.B. 234: 218-220, 1971. [PubMed: 5288810] [Full Text: https://doi.org/10.1038/newbio234218a0]

  817. Old, J. M., Ward, R. H. T., Petrou, M., Karagozlu, F., Modell, B., Weatherall, D. J. First-trimester fetal diagnosis for hemoglobinopathies: three cases. Lancet 320: 1413-1416, 1982. Note: Originally Volume II. [PubMed: 6129504] [Full Text: https://doi.org/10.1016/s0140-6736(82)91324-1]

  818. Opfell, R. W., Lorkin, P. A., Lehmann, H. Hereditary non-spherocytic haemolytic anaemia with post-splenectomy inclusion bodies and pigmenturia caused by an unstable haemoglobin Santa Ana--beta 88 (F4) leucine-proline. J. Med. Genet. 5: 292-297, 1968. [PubMed: 5713642] [Full Text: https://doi.org/10.1136/jmg.5.4.292]

  819. Oppenheim, A., Oron, V., Filon, D., Fearon, C. C., Rachmilewitz, E. A., Kazazian, H. H., Jr., Rund, D. Sporadic alleles, including a novel mutation, characterize beta-thalassemia in Ashkenazi Jews. Hum. Mutat. 2: 155-157, 1993. [PubMed: 8318995] [Full Text: https://doi.org/10.1002/humu.1380020219]

  820. Oribe, Y., Hamaguchi, K., Kusuda, Y., Harano, K., Harano, T., Iwasaki, Y., Kotegawa, K., Sakata, T. Hb Tsukumi (beta-117(G19)his-to-tyr): a new hemoglobin variant found in a Japanese male. Hemoglobin 24: 117-123, 2000. [PubMed: 10870882] [Full Text: https://doi.org/10.3109/03630260009003430]

  821. Orkin, S. H., Alter, B. P., Altay, C., Mahoney, M. J., Lazarus, H., Hobbins, J. C., Nathan, D. G. Application of endonuclease mapping to the analysis and prenatal diagnosis of thalassemias caused by globin-gene deletion. New Eng. J. Med. 299: 166-172, 1978. [PubMed: 661890] [Full Text: https://doi.org/10.1056/NEJM197807272990403]

  822. Orkin, S. H., Antonarakis, S. E., Loukopoulos, D. Abnormal processing of beta(Knossos) RNA. Blood 64: 311-313, 1984. [PubMed: 6733281]

  823. Orkin, S. H., Cheng, T.-C., Antonarakis, S. E., Kazazian, H. H., Jr. Thalassemia due to a mutation in the cleavage-polyadenylation signal of the human beta-globin gene. EMBO J. 4: 453-456, 1985. [PubMed: 4018033] [Full Text: https://doi.org/10.1002/j.1460-2075.1985.tb03650.x]

  824. Orkin, S. H., Goff, S. C. Nonsense and frameshift mutations in beta-thalassemia detected in cloned beta-globin genes. J. Biol. Chem. 256: 9782-9784, 1981. [PubMed: 6985481]

  825. Orkin, S. H., Kazazian, H. H., Jr., Antonarakis, S. E., Goff, S. C., Boehm, C. D., Sexton, J. P., Waber, P. G., Giardina, P. J. V. Linkage of beta-thalassaemic mutations and beta-globin gene polymorphisms with DNA polymorphisms in the human beta-globin gene cluster. Nature 296: 627-631, 1982. [PubMed: 6280057] [Full Text: https://doi.org/10.1038/296627a0]

  826. Orkin, S. H., Kazazian, H. H., Jr., Antonarakis, S. E., Ostrer, H., Goff, S. C., Sexton, J. P. Abnormal RNA processing due to the exon mutation of beta-E-globin gene. Nature 300: 768-769, 1982. [PubMed: 7177196] [Full Text: https://doi.org/10.1038/300768a0]

  827. Orkin, S. H., Kolodner, R., Michelson, A., Husson, R. Cloning and direct examination of a structurally abnormal human beta-zero-thalassemia globin gene. Proc. Nat. Acad. Sci. 77: 3558-3562, 1980. [PubMed: 6251466] [Full Text: https://doi.org/10.1073/pnas.77.6.3558]

  828. Orkin, S. H., Little, P. F. R., Kazazian, H. H., Jr., Boehm, C. D. Improved detection of the sickle mutation by DNA analysis: application to prenatal diagnosis. New Eng. J. Med. 307: 32-36, 1982. [PubMed: 6176867] [Full Text: https://doi.org/10.1056/NEJM198207013070106]

  829. Orkin, S. H., Old, J. M., Weatherall, D. J., Nathan, D. G. Partial deletion of beta-globin gene DNA in certain patients with beta-zero-thalassemia. Proc. Nat. Acad. Sci. 76: 2400-2404, 1979. [PubMed: 287080] [Full Text: https://doi.org/10.1073/pnas.76.5.2400]

  830. Orkin, S. H., Sexton, J. P., Cheng, T.-C., Goff, S. C., Giardina, P. J. V., Lee, J. I., Kazazian, H. H., Jr. ATA box transcription mutation in beta-thalassemia. Nucleic Acids Res. 11: 4727-4734, 1983. [PubMed: 6308558] [Full Text: https://doi.org/10.1093/nar/11.14.4727]

  831. Orkin, S. H., Sexton, J. P., Goff, S. C., Kazazian, H. H., Jr. Inactivation of an acceptor RNA splice site by a short deletion in beta-thalassemia. J. Biol. Chem. 258: 7249-7251, 1983. [PubMed: 6190800]

  832. Oron, V., Filon, D., Oppenheim, A., Rund, D. Severe thalassaemia intermedia caused by interaction of homozygosity for alpha-globin gene triplication with heterozygosity for beta zero-thalassaemia. Brit. J. Haemat. 86: 377-379, 1994. [PubMed: 8199028] [Full Text: https://doi.org/10.1111/j.1365-2141.1994.tb04743.x]

  833. Orringer, E. P., Felice, A., Reese, A., Wilson, J. B., Lam, H., Gravely, M. E., Huisman, T. H. J. Hemoglobin Nottingham (beta (FG5) 98 val-to-gly) in a Caucasian male: clinical and biosynthetic studies. Hemoglobin 2: 315-332, 1978. [PubMed: 701088] [Full Text: https://doi.org/10.3109/03630267809005343]

  834. Osgood, E. E., Jones, R. T., Brimhall, B., Koler, R. D. Hemoglobin Yakima: clinical and biochemical studies. (Abstract) Clin. Res. 15: 134, 1967.

  835. Ottolenghi, S., Comi, P., Giglioni, B., Tolstoshev, P., Lanyon, W. G., Mitchell, G. J., Williamson, R., Russo, G., Musumeci, S., Schilliro, G., Tsistrakis, G. A., Charache, S., Wood, W. G., Clegg, J. B., Weatherall, D. J. Delta-beta-thalassemia is due to a gene deletion. Cell 9: 71-80, 1976. [PubMed: 975241] [Full Text: https://doi.org/10.1016/0092-8674(76)90053-2]

  836. Ottolenghi, S., Giglioni, B. The deletion in a type of delta-zero-beta-zero-thalassemia begins in an inverted AluI repeat. Nature 300: 770-771, 1982. [PubMed: 6184621] [Full Text: https://doi.org/10.1038/300770a0]

  837. Ottolenghi, S., Lanyon, W. G., Paul, J., Williamson, R., Weatherall, D. J., Clegg, J. B., Pritchard, J., Pootrakul, S., Boon, W. H. Gene deletion as the cause of alpha-thalassaemia: the severe form of alpha thalassaemia is caused by haemoglobin gene deletion. Nature 251: 389-391, 1974. [PubMed: 4138824] [Full Text: https://doi.org/10.1038/251389a0]

  838. Ottolenghi, S., Lanyon, W. G., Williamson, R., Weatherall, D. J., Clegg, J. B., Pitcher, C. S. Human globin gene analysis for a patient with 'beta-zero: delta-beta-zero' thalassemia. Proc. Nat. Acad. Sci. 72: 2294-2299, 1975. [PubMed: 49057] [Full Text: https://doi.org/10.1073/pnas.72.6.2294]

  839. Outeirino, J., Casey, R., White, J. M., Lehmann, H. Haemoglobin Madrid beta 115 (G17) alanine-to-proline: an unstable variant associated with haemolytic anaemia. Acta Haemat. 52: 53-60, 1974. [PubMed: 4212046] [Full Text: https://doi.org/10.1159/000208220]

  840. Owen, M. C., Ockelford, P. A., Wells, R. M. G. HB Howick (beta37 (C3) trp-to-gly): a new high oxygen affinity variant of the alpha-1-beta-2 contact. Hemoglobin 17: 513-521, 1993. [PubMed: 8144352] [Full Text: https://doi.org/10.3109/03630269309043491]

  841. Ozsoylu, S. Homozygous hemoglobin D Punjab. Acta Haemat. 43: 353-359, 1970. [PubMed: 4991321] [Full Text: https://doi.org/10.1159/000208751]

  842. Padanilam, B. J., Huisman, T. H. J. The beta-0-thalassemia in an American black family is due to a single nucleotide substitution in the acceptor splice junction of the second intervening sequence. Am. J. Hemat. 22: 259-263, 1986. [PubMed: 2424301] [Full Text: https://doi.org/10.1002/ajh.2830220306]

  843. Pagano, L., Lacerra, G., Camardella, L., De Angioletti, M., Fioretti, G., Maglione, G., de Bonis, C., Guarino, E., Viola, A., Cutolo, R., De Rosa, L., Carestia, C. Hemoglobin Neapolis, beta-126(H4)val-to-gly: a novel beta-chain variant associated with a mild beta-thalassemia phenotype and displaying anomalous stability features. Blood 78: 3070-3075, 1991. [PubMed: 1954392]

  844. Pagano, L., Salzano, A. M., Carbone, V., Iannelli, D., Viola, A., Pollio, F., Prossomariti, L., David, O., Ricco, G., Pucci, P. Hb Cardarelli [beta-86(F2)ala-to-pro]: a new unstable and hyperaffine variant in association with beta(+)-thalassemia. Hemoglobin 28: 103-115, 2004. [PubMed: 15182052] [Full Text: https://doi.org/10.1081/hem-120035915]

  845. Pagnier, J., Baudin-Chich, V., Lacaze, N., Bohn, B., Poyart, C. Haemoglobin beta23 val-to-ile produced in Escherichia coli facilitates Hb S polymerization. Brit. J. Haemat. 74: 531-534, 1990. [PubMed: 2189492] [Full Text: https://doi.org/10.1111/j.1365-2141.1990.tb06346.x]

  846. Pagnier, J., Mears, J. G., Dunda-Belkhodja, O., Schaefer-Rego, K. E., Beldjord, C., Nagel, R. L., Labie, D. Evidence for the multicentric origin of the sickle cell hemoglobin gene in Africa. Proc. Nat. Acad. Sci. 81: 1771-1773, 1984. [PubMed: 6584911] [Full Text: https://doi.org/10.1073/pnas.81.6.1771]

  847. Paniker, N. V., Lin, K. D., Krantz, S. B., Flexner, J. M., Wasserman, B. K., Puett, D. Hemoglobin Vanderbilt (beta 89 ser-to-arg): a new hemoglobin with high oxygen affinity and compensatory erythrocytosis. Brit. J. Haemat. 39: 249-258, 1978. [PubMed: 678476] [Full Text: https://doi.org/10.1111/j.1365-2141.1978.tb01095.x]

  848. Papassotiriou, I., Traeger-Synodinos, J., Prome, D., Kister, J., Vrettou, C., Xaidara, A., Marden, M., Stamoulakatou, A., Wajcman, H., Kanavakis, E. Hb Sitia (beta-128(H6)ala-to-val): an unstable variant with a substitution in the alpha-1-beta-1 interface. Hemoglobin 25: 45-56, 2001. [PubMed: 11300349] [Full Text: https://doi.org/10.1081/hem-100103069]

  849. Park, S. S., Barnetson, R., Kim, S. W., Weatherall, D. J., Thein, S. L. A spontaneous deletion of beta33/34 val in exon 2 of the beta globin gene (Hb Korea) produces the phenotype of dominant beta thalassaemia. Brit. J. Haemat. 78: 581-582, 1991. [PubMed: 1911355] [Full Text: https://doi.org/10.1111/j.1365-2141.1991.tb04499.x]

  850. Pasvol, G. Protective hemoglobinopathies and Plasmodium falciparum transmission. Nature Genet. 42: 284-285, 2010. [PubMed: 20348963] [Full Text: https://doi.org/10.1038/ng0410-284]

  851. Pauling, L., Itano, H. A., Singer, S. J., Wells, I. C. Sickle cell anemia, a molecular disease. Science 110: 543-548, 1949. [PubMed: 15395398] [Full Text: https://doi.org/10.1126/science.110.2865.543]

  852. Pearson, H. A., Gallagher, D., Chilcote, R., Sullivan, E., Wilimas, J., Espeland, M., Ritchey, A. K., Cooperative Study of Sickle Cell Disease. Developmental pattern of splenic dysfunction in sickle cell disorders. Pediatrics 76: 392-397, 1985. [PubMed: 2412200]

  853. Perea, F. J., Magana, M. T., Esparza, M. A., Ibarra, B. A frameshift at codons 77/78 (-C): a novel beta-thalassemia mutation. Hemoglobin 28: 261-265, 2004. [PubMed: 15481896] [Full Text: https://doi.org/10.1081/hem-120040220]

  854. Perichon, B., Ragusa, A., Lapoumeroulie, C., Romand, A., Moi, P., Ikuta, T., Labie, D., Elion, J., Krishnamoorthy, R. Inter-ethnic polymorphism of the beta-globin gene locus control region (LCR) in sickle-cell anemia patients. Hum. Genet. 91: 464-468, 1993. [PubMed: 8314558] [Full Text: https://doi.org/10.1007/BF00217773]

  855. Perrault, J., Fairbanks, V. F., McCormick, D. J., Kubik, K., Madden, B. J., Holmes, M. W., Hoyer, J. D. Hemoglobin Rockford, beta68(E12)leu-to-phe: a new HB variant associated with mild anemia. (Abstract) Blood 90 (Suppl. 1): 30b, 1997.

  856. Persons, D. A., Nienhuis, A. W. Gene therapy for the hemoglobin disorders: past, present, and future. (Commentary) Proc. Nat. Acad. Sci. 97: 5022-5024, 2000. [PubMed: 10805762] [Full Text: https://doi.org/10.1073/pnas.97.10.5022]

  857. Perutz, M. F., Fermi, G., Shih, T.-B. Structure of deoxyhemoglobin Cowtown (HC3(146)beta his-to-leu): origin of the alkaline Bohr effect and electrostatic interactions in hemoglobin. Proc. Nat. Acad. Sci. 81: 4781-4784, 1984. [PubMed: 6589624] [Full Text: https://doi.org/10.1073/pnas.81.15.4781]

  858. Perutz, M. F., Lehmann, H. Molecular pathology of human hemoglobin. Nature 219: 902-909, 1968. [PubMed: 5691676] [Full Text: https://doi.org/10.1038/219902a0]

  859. Perutz, M. F., Pulsinelli, P. D., Ranney, H. M. Structure and subunit interaction of haemoglobin M Milwaukee. Nature N.B. 237: 259-263, 1972. [PubMed: 4338724] [Full Text: https://doi.org/10.1038/newbio237259a0]

  860. Perutz, M. F., Pulsinelli, P., Eyck, L. T., Kilmartin, J. V., Shibata, S., Miyaji, Y., Iuchi, I., Hamilton, H. B. Haemoglobin Hiroshima and the mechanism of the alkaline Bohr effect. Nature N.B. 232: 147-149, 1971. [PubMed: 5285571] [Full Text: https://doi.org/10.1038/newbio232147a0]

  861. Peters, J., Andrews, S. J., Loutit, J. F., Clegg, J. B. A mouse beta-globin mutant that is an exact model of hemoglobin Rainier in man. Genetics 110: 709-721, 1985. [PubMed: 3839762] [Full Text: https://doi.org/10.1093/genetics/110.4.709]

  862. Peterson, K. R., Clegg, C. H., Navas, P. A., Norton, E. J., Kimbrough, T. G., Stamatoyannopoulos, G. Effect of deletion of 5-prime HS3 or 5-prime HS2 of the human beta-globin locus control region on the developmental regulation of globin gene expression in beta-globin locus yeast artificial chromosome transgenic mice. Proc. Nat. Acad. Sci. 93: 6605-6609, 1996. [PubMed: 8692864] [Full Text: https://doi.org/10.1073/pnas.93.13.6605]

  863. Philippe, M., Larondelle, Y., Vaerman, J. L., Martiat, P., Galacteros, F., Wajcman, H., Lambert, M. Hb Tubingen [beta-106(G8) leu-to-gln] in a Belgian family. Hemoglobin 17: 373-378, 1993. [PubMed: 8226097] [Full Text: https://doi.org/10.3109/03630269308997490]

  864. Pierce, L. E., Rath, C. E., McCoy, K. A new hemoglobin variant with sickling properties. New Eng. J. Med. 268: 862-866, 1963. [PubMed: 13943409] [Full Text: https://doi.org/10.1056/NEJM196304182681603]

  865. Pillers, D. M., Jones, M., Head, C., Jones, R. T. Hb Hope [beta-136(H14)gly-to-asp] and Hb E [beta-26(B8)glu-to-lys]: compound heterozygosity in a Thai Mien family. Hemoglobin 16: 81-84, 1992. [PubMed: 1634366] [Full Text: https://doi.org/10.3109/03630269209005680]

  866. Pinkerton, P. H., Wilson, J. B., Lam, H., Williams, D., Huisman, T. H. J. Hemoglobin Riyadh-beta (zero)-thalassemia in an Indian family. Hemoglobin 3: 451-458, 1979. [PubMed: 511584] [Full Text: https://doi.org/10.3109/03630267909002281]

  867. Pirastu, M., del Senno, L., Conconi, F., Vullo, C., Kan, Y. W. Ferrara beta-zero-thalassaemia caused by the beta-39 nonsense mutation. Nature 307: 76, 1984. [PubMed: 6690987] [Full Text: https://doi.org/10.1038/307076a0]

  868. Pirastu, M., Galanello, R., Doherty, M. A., Tuveri, T., Cao, A., Kan, Y. W. The same beta-globin gene mutation is present on nine different beta-thalassemia chromosomes in a Sardinian population. Proc. Nat. Acad. Sci. 84: 2882-2885, 1987. [PubMed: 3033668] [Full Text: https://doi.org/10.1073/pnas.84.9.2882]

  869. Pirastu, M., Kan, Y. W., Lin, C. C., Baine, R. M., Holbrook, C. T. Hemolytic disease of the newborn caused by a new deletion of the entire beta-globin cluster. J. Clin. Invest. 72: 602-609, 1983. [PubMed: 6308057] [Full Text: https://doi.org/10.1172/JCI111008]

  870. Pirastu, M., Ristaldi, M. S., Loudianos, G., Murru, S., Sciarratta, G. V., Parodi, M. I., Leone, D., Agosti, S., Cao, A. Molecular analysis of atypical beta-thalassemia heterozygotes. Ann. N.Y. Acad. Sci. 612: 90-97, 1990. [PubMed: 2291578] [Full Text: https://doi.org/10.1111/j.1749-6632.1990.tb24294.x]

  871. Pisciotta, A. V., Ebbe, S. N., Hinz, J. E. Clinical and laboratory features of two variants of methemoglobin-M disease. J. Lab. Clin. Med. 54: 73-87, 1959. [PubMed: 13665153]

  872. Pistidda, P., Cherchi, L., Corda, M., Guiso, L., Pardini, S., Pirastru, M., Manca, L., Longinotti, M., Masala, B. Hb Tigraye [beta-79(EF3)asp-his] in a Caucasian family from Sardinia. Hemoglobin 25: 341-345, 2001. [PubMed: 11570729] [Full Text: https://doi.org/10.1081/hem-100105229]

  873. Plaseska, D., de Alarcon, P. A., McMillan, S., Walbrecht, M., Wilson, J. B., Huisman, T. H. J. Hb Iowa or beta119(GH2)gly-to-ala. Hemoglobin 14: 423-429, 1990. [PubMed: 2283296] [Full Text: https://doi.org/10.3109/03630269009032002]

  874. Plaseska, D., Dimovski, A. J., Jankovic, L., Sukarova, E., Efremov, G. D., Gebauer, E., Jerance, D. Hb Hoshida [beta-43(CD2)glu-to-gln] observed in a Yugoslavian family. Hemoglobin 15: 541-543, 1991. [PubMed: 1814859] [Full Text: https://doi.org/10.3109/03630269109027902]

  875. Plaseska, D., Dimovski, A. J., Wilson, J. B., Webber, B. B., Hume, H. A., Huisman, T. H. J. Hb Montreal, a new variant with an extended beta chain due to a deletion of asp, gly, leu at positions 73, 74, and 75, and an insertion of ala, arg, cys, gln at the same location. Blood 77: 178-181, 1991. [PubMed: 1845844]

  876. Plaseska, D., Jankovic, L., Dimovski, A. J., Milenovic, D., Juricic, D., Efremov, G. D. Hb Yokohama [beta-31(B13)leu-to-pro] detected as a de novo mutation in a Yugoslavian boy. Hemoglobin 15: 469-476, 1991. [PubMed: 1814855] [Full Text: https://doi.org/10.3109/03630269109027894]

  877. Plaseska, D., Wilson, J. B., Gu, L.-H., Kutlar, F., Huisman, T. H. J., Zeng, Y.-T., Shen, M. Hb Zengcheng or beta114(G16)leu-to-met. Hemoglobin 14: 555-557, 1990. [PubMed: 2079435] [Full Text: https://doi.org/10.3109/03630269009005808]

  878. Plaseska-Karanfilska, D., de Weinstein, B. I., Efremov, G. D. Hb Rambam (beta-69(E13)gly-to-asp)/beta-0-thalassemia (codon 5 [-CT]) in a family from Argentina. Hemoglobin 24: 157-161, 2000. [PubMed: 10870889] [Full Text: https://doi.org/10.3109/03630260009003437]

  879. Plaseska-Karanfilska, D., Song, K. S., Efremov, G. D. Hb Old Dominion/Burton-upon-Trent or beta-143(H21)his-to-tyr, found in a diabetic woman from Korea. Hemoglobin 24: 323-326, 2000. [PubMed: 11186263] [Full Text: https://doi.org/10.3109/03630260008993140]

  880. Platt, O. S., Brambilla, D. J., Rosse, W. F., Milner, P. F., Castro, O., Steinberg, M. H., Klug, P. P. Mortality in sickle cell disease: life expectancy and risk factors for early death. New Eng. J. Med. 330: 1639-1644, 1994. [PubMed: 7993409] [Full Text: https://doi.org/10.1056/NEJM199406093302303]

  881. Podda, A., Galanello, R., Maccioni, L., Melis, M. A., Perseu, L., Ruggeri, R., Addis, M., Cao, A. A new unstable hemoglobin variant producing a beta-thalassemia-like phenotype. (Abstract) 3rd International Conference on Thalassemia and the Hemoglobinopathies, Sardinia, April 1989. P. 51.

  882. Podda, A., Galanello, R., Maccioni, L., Melis, M. A., Rosatelli, C., Perseu, L., Cao, A. Hemoglobin Cagliari (beta60 [E4] val-to-glu): a novel unstable thalassemic hemoglobinopathy. Blood 77: 371-375, 1991. [PubMed: 1985702]

  883. Poncz, M., Ballantine, M., Solowiejczyk, D., Barak, I., Schwartz, E., Surrey, S. Beta-thalassemia in a Kurdish Jew. J. Biol. Chem. 257: 5994-5996, 1982. [PubMed: 7076659]

  884. Pootrakul, S. N., Wasi, P., Na-Nakorn, S. Haemoglobin J-Bangkok: a clinical, haematological and genetical study. Brit. J. Haemat. 13: 303-309, 1967. [PubMed: 6025242] [Full Text: https://doi.org/10.1111/j.1365-2141.1967.tb08744.x]

  885. Popp, R. A., Popp, D. M., Shinpock, S. G., Yang, M. Y., Mural, J. G., Aguinaga, M. P., Kopsombut, P., Roa, P. D., Turner, E. A., Rubin, E. M. A transgenic mouse model of hemoglobin S Antilles disease. Blood 89: 4204-4212, 1997. [PubMed: 9166865]

  886. Powars, D., Schroeder, W. A., Shelton, J. R., Evans, L., Vinetz, R. An individual with hemoglobins S and Deer Lodge. Hemoglobin 1: 97-100, 1977.

  887. Poyart, C., Bursaux, E., Teisseire, B., Freminet, A., Duvelleroy, M., Rosa, J. Hemoglobin Creteil: oxygen transport by erythrocytes: in vitro and in vivo studies in a high oxygen-affinity mutant. Ann. Intern. Med. 88: 758-763, 1978. [PubMed: 27132] [Full Text: https://doi.org/10.7326/0003-4819-88-6-758]

  888. Poyart, C., Schaad, O., Kister, J., Galacteros, F., Edelstein, S. J., Blouquit, Y., Arous, N. Hemoglobin Saint Mande (beta-102 (G4) asn-to-tyr): functional studies and structural modeling reveal an altered T state. Europ. J. Biochem. 194: 343-348, 1990. [PubMed: 2269272] [Full Text: https://doi.org/10.1111/j.1432-1033.1990.tb15624.x]

  889. Praxedes, H., Wiltshire, B. G., Lorkin, P. A., Lehmann, H. Cited by Lehmann, H. In: Martin, H.; Nowicki, J. F. (eds.): Int. Symp. 'Synthese, Struktur und Funktion des Hamoglobins,' Bad Nauheim, April, 1972. Munich: Lehmanns (pub.) 1972. Pp. 359-379.

  890. Prchal, J. T., Cashman, D. P., Kan, Y. W. Hemoglobin Long Island is caused by a single mutation (adenine to cytosine) resulting in a failure to cleave amino-terminal methionine. Proc. Nat. Acad. Sci. 83: 24-27, 1986. [PubMed: 3455755] [Full Text: https://doi.org/10.1073/pnas.83.1.24]

  891. Prehu, C., Behnken, L. J., Neumann, R., Riou, J., Kister, J., Kiger, L., Prome, D., Arndt, T., Semmelroggen, B., Schmidt, M., Galacteros, F., Wajcman, H. A new unstable hemoglobin variant with low oxygen affinity: Hb Ilmenau [beta-41(C7)phe-to-cys]. Hemoglobin 26: 169-174, 2002. [PubMed: 12144060] [Full Text: https://doi.org/10.1081/hem-120005455]

  892. Prehu, C., Riou, J., Sartelet, I, Prome, D., Claparols, C., Denier, M., Motte, J., Galacteros, F., Wajcman, H. Hb O-Tibesti [beta-121(GH4)glu-to-lys; beta-11(A8)val-to-ile], a hemoglobin variant carrying in the same beta chain the substitutions of Hb O-Arab and Hb Hamilton, found in combination with Hb S [beta-6(A3)glu-to-val]. Hemoglobin 26: 13-20, 2002. [PubMed: 11939508] [Full Text: https://doi.org/10.1081/hem-120002936]

  893. Premawardhena, A., Fisher, C. A., Fathiu, F., de Silva, S., Perera, W., Peto, T. E. A., Olivieri, N. F., Weatherall, D. J. Genetic determinants of jaundice and gallstones in haemoglobin E beta-thalassemia. Lancet 357: 1945-1946, 2001. [PubMed: 11425418] [Full Text: https://doi.org/10.1016/s0140-6736(00)05082-0]

  894. Premawardhena, A., Fisher, C. A., Liu, Y. T., Verma, I. C., de Silva, S., Arambepola, M., Clegg, J. B., Weatherall, D. J. The global distribution of length polymorphisms of the promoters of the glucuronosyltransferase 1 gene (UGT1A1): hematologic and evolutionary implications. Blood Cells Molec. Dis. 31: 98-101, 2003. [PubMed: 12850492] [Full Text: https://doi.org/10.1016/s1079-9796(03)00071-8]

  895. Premawardhena, A., Fisher, C. A., Olivieri, N. F., de Silva, S., Arambepola, M., Perera, W., O'Donnell, A., Peto, T. E. A., Viprakasit, V., Merson, L., Muraca, G., Weatherall, D. J. Haemoglobin E beta-thalassemia in Sri Lanka. Lancet 366: 1467-1470, 2005. [PubMed: 16243092] [Full Text: https://doi.org/10.1016/S0140-6736(05)67396-5]

  896. Prezant, T. R., Fischel-Ghodsian, N. Trapped-oligonucleotide nucleotide incorporation (TONI) assay, a simple method for screening point mutations. Hum. Mutat. 1: 159-164, 1992. [PubMed: 1301203] [Full Text: https://doi.org/10.1002/humu.1380010212]

  897. Pribilla, W., Klesse, P., Betke, K., Lehmann, H., Beale, D. Haemoglobin Koln disease: familial hypochromic hemolytic anemia with hemoglobin anomaly. Klin. Wschr. 43: 1049-1053, 1965. [PubMed: 5881530] [Full Text: https://doi.org/10.1007/BF01746594]

  898. Pribilla, W. Thalassemie-aehnliche Erkrankung mit neuem minor-Hb (Hb Koln). In: Lehmann, H.; Betke, K.: Haemoglobin-Colloquium. Stuttgart: Georg Thieme Verlag (pub.) 1962. Pp. 1-14.

  899. Price, P. M., Conover, J. H., Hirschhorn, K. Chromosomal localization of human hemoglobin structural genes. Nature 237: 340-342, 1972. [PubMed: 4557400] [Full Text: https://doi.org/10.1038/237340a0]

  900. Prior, J. F., Raven, J. L., Wilson, J. B., Kutlar, A., Kutlar, F., Huisman, T. H. J. Hb J-Lome or beta59 (E3) lys-to-asn in a Vietnamese family. Hemoglobin 13: 79-81, 1989. [PubMed: 2703367] [Full Text: https://doi.org/10.3109/03630268908998055]

  901. Proudfoot, N. J., Shander, M. H. M., Manley, J. L., Gefter, M. L., Maniatis, T. Structure and in vitro transcription of human globin genes. Science 209: 1329-1336, 1980. [PubMed: 6158093] [Full Text: https://doi.org/10.1126/science.6158093]

  902. Puett, D., Paniker, N. V., Lin, K. D., Flexner, J. M., Wasserman, B. K., Krantz, S. B. Hemoglobin Vanderbilt (beta 89 (F5) ser-to-arg): a new hemoglobin mutant with increased oxygen affinity and lowered response to 2,3-diphosphoglycerate. (Abstract) Clin. Res. 25: 53A, 1977.

  903. Qin, W.-B., Pobedimskaya, D. D., Molchanova, T. P., Wilson, J. B., Gu, L.-H., de Pablos, J. M., Huisman, T. H. J. Hb Fannin-Lubbock in five Spanish families is characterized by two mutations: beta-111 GTC-to-CTC (val-to-leu) and beta-119 GGC-to-GAC (gly-to-asp). Hemoglobin 18: 297-306, 1994. [PubMed: 7852084] [Full Text: https://doi.org/10.3109/03630269408996195]

  904. Qualtieri, A., Le Pera, M., Pedace, V., Magariello, A., Brancati, C. Hb Molfetta (beta-126(H4)val-to-leu, GTG-to-CTG): a new, silent, neutral beta chain variant found in an Italian woman. Hemoglobin 26: 7-12, 2002. [PubMed: 11939515] [Full Text: https://doi.org/10.1081/hem-120002935]

  905. Quarum, M., Shih, T., Jones, R. T. Oxygen equilibrium studies of Hb Willamette, beta51(D2)pro-to-arg. Hemoglobin 7: 57-69, 1983. [PubMed: 6841127] [Full Text: https://doi.org/10.3109/03630268309038401]

  906. Quattrin, N., Ventruto, V., De Rosa, L. Hemoglobinopathies in Campania with particular reference to the rare and new types. Blut 20: 292-295, 1970. [PubMed: 5447151] [Full Text: https://doi.org/10.1007/BF01632131]

  907. Ragusa, A., Lombardo, M., Sortino, G., Lombardo, T., Nagel, R. L., Labie, D. Beta-S gene in Sicily is in linkage disequilibrium with the Benin haplotype: implications for gene flow. Am. J. Hemat. 27: 139-141, 1988. [PubMed: 2893541] [Full Text: https://doi.org/10.1002/ajh.2830270214]

  908. Rahbar, S., Asmerom, Y., Blume, K. G. A silent hemoglobin variant detected by HPLC: hemoglobin City of Hope beta69 (E13) gly-to-ser. Hemoglobin 8: 333-342, 1984. [PubMed: 6434492] [Full Text: https://doi.org/10.3109/03630268408991716]

  909. Rahbar, S., Beale, D., Isaacs, W. A., Lehmann, H. Abnormal haemoglobins in Iran: observations of a new variant--haemoglobin J Iran (beta 77 his-to-asp). Brit. Med. J. 1: 674-677, 1967. [PubMed: 6019668] [Full Text: https://doi.org/10.1136/bmj.1.5541.674]

  910. Rahbar, S., Feagler, R. J., Beutler, E. Hemoglobin Hammersmith, beta 42 (CD1) phe-to-ser, associated with severe hemolytic anemia. Hemoglobin 5: 97-105, 1981. [PubMed: 6259091] [Full Text: https://doi.org/10.3109/03630268108996914]

  911. Rahbar, S., Lee, T., Asmeron, Y. Hb Beckman alpha135 (H13) ala-to-glu: a new unstable variant and reduced oxygen affinity. (Abstract) Blood 78 (suppl. 1): 204a, 1991.

  912. Rahbar, S., Louis, J., Lee, T., Asmerom, Y. Hemoglobin North Chicago (beta36 (C2) proline-to-serine): a new high affinity hemoglobin. Hemoglobin 9: 559-576, 1985. [PubMed: 3937824] [Full Text: https://doi.org/10.3109/03630268508997038]

  913. Rahbar, S., Nowzari, G., Ala, F. Haemoglobin Avicenna (beta47 (CD6) asp-to-ala), a new abnormal haemoglobin. Biochim. Biophys. Acta 576: 466-470, 1979. [PubMed: 427203] [Full Text: https://doi.org/10.1016/0005-2795(79)90421-5]

  914. Rahbar, S., Nowzari, G., Haydari, H., Kaneshmand, P. Hemoglobin Hamadan: beta 56 gly-to-arg. Biochim. Biophys. Acta 379: 645-648, 1975. [PubMed: 1122305] [Full Text: https://doi.org/10.1016/0005-2795(75)90171-3]

  915. Rahbar, S., Rea, C., Blume, K., Seltzer, D., Feiner, R. A second case of hemoglobin McKees Rocks (beta145 tyr-to-term): a variant with premature termination of the beta-chain. Hemoglobin 7: 97-104, 1983. [PubMed: 6841128] [Full Text: https://doi.org/10.3109/03630268309038406]

  916. Rahbar, S., Rosen, R., Nozari, G., Lee, T. D., Asmerom, Y., Wallace, R. B. Hemoglobin Pasadena: identification of the gene mutant by DNA analysis using synthetic DNA probes. Am. J. Hemat. 27: 204-208, 1988. [PubMed: 3348204] [Full Text: https://doi.org/10.1002/ajh.2830270310]

  917. Rahbar, S., Winkler, K., Louis, J., Rea, C., Blume, K., Beutler, E. Hemoglobin Great Lakes (beta68 (E12) leucine to histidine): a new high-affinity hemoglobin. Blood 58: 813-817, 1981. [PubMed: 7272510]

  918. Rahbar, S. Haemoglobin D Iran: beta 22 glutamic acid to glutamine (B4). Brit. J. Haemat. 24: 31-36, 1973. [PubMed: 4715135] [Full Text: https://doi.org/10.1111/j.1365-2141.1973.tb05724.x]

  919. Ramachandran, M., Gu, L.-H., Wilson, J. B., Kitundu, M. N., Adekile, A. D., Liu, J.-C., McKie, K. M., Huisman, T. H. J. A new variant, Hb Muscat [beta32 (B14) leu-to-val] observed in association with Hb S in an Arabian family. Hemoglobin 16: 259-266, 1992. [PubMed: 1517102] [Full Text: https://doi.org/10.3109/03630269208998866]

  920. Ramot, B., Fisher, S., Remez, D., Schneerson, R., Kahane, D., Ager, J. A. M., Lehmann, H. Haemoglobin O in an Arab family: sickle-cell haemoglobin O trait. Brit. Med. J. 2: 1262-1264, 1960. [PubMed: 20788973] [Full Text: https://doi.org/10.1136/bmj.2.5208.1262]

  921. Ramsay, M., Jenkins, T. Globin gene--associated restriction-fragment-length polymorphisms in Southern African peoples. Am. J. Hum. Genet. 41: 1132-1144, 1987. [PubMed: 2891298]

  922. Ranney, H. M., Jacobs, A. S., Nagel, R. L. Haemoglobin New York. Nature 213: 876-878, 1967. [PubMed: 6030043] [Full Text: https://doi.org/10.1038/213876a0]

  923. Ranney, H. M., Jacobs, A. S., Udem, L., Zalusky, R. Hemoglobin Riverdale-Bronx: an unstable hemoglobin resulting from the substitution of arginine for glycine at helical residue B6 of the beta polypeptide chain. Biochem. Biophys. Res. Commun. 33: 1004-1011, 1968. [PubMed: 5705748] [Full Text: https://doi.org/10.1016/0006-291x(68)90413-0]

  924. Ranney, H. M., Larson, D. L., McCormack, G. H., Jr. Some clinical, biochemical and genetic observations on hemoglobin C. J. Clin. Invest. 32: 1277-1284, 1953. [PubMed: 13108995] [Full Text: https://doi.org/10.1172/JCI102856]

  925. Reed, C. S., Hampson, R., Gordon, S., Jones, R. T., Novy, M. J., Brimhall, B., Edwards, M. J., Koler, R. D. Erythrocytosis secondary to increased oxygen affinity of a mutant hemoglobin, hemoglobin Kempsey. Blood 31: 623-632, 1968. [PubMed: 5651043]

  926. Rees, D. C., Duley, J., Simmonds, H. A., Wonke, B., Thein, S. L., Clegg, J. B., Weatherall, D. J. Interaction of hemoglobin E and pyrimidine 5-prime nucleotidase deficiency. Blood 88: 2761-2767, 1996. [PubMed: 8839873]

  927. Rees, D. C., Rochette, J., Schofield, C., Green, B., Morris, M., Parker, N. E., Sasaki, H., Tanaka, A., Ohba, Y., Clegg, J. B. A novel silent posttranslational mechanism converts methionine to aspartate in hemoglobin Bristol (beta-67(E11) val-met-to-asp). Blood 88: 341-348, 1996. [PubMed: 8704193]

  928. Reissmann, K. R., Ruth, W. E., Nomura, T. A human hemoglobin with lowered oxygen affinity and impaired heme-heme interactions. J. Clin. Invest. 40: 1826-1833, 1961. [PubMed: 14491349] [Full Text: https://doi.org/10.1172/JCI104406]

  929. Ren, Y., Chen, S. S., Liang, C. C., Zhang, M. J., Huang, M. X., Zhang, G. L., Zen, X. S. Hb D-Ouled Rabah (beta-19(B1)asn-to-lys): a rare beta-chain variant found in a Chinese family. Hemoglobin 12: 77-79, 1988. [PubMed: 3384702] [Full Text: https://doi.org/10.3109/03630268808996886]

  930. Renda, M., Maggio, A., Warren, T. C., Kazazian, H. H., Jr. Detection of an IVS-1 3-prime end (G-C) beta-thalassemia mutation in the AG invariant dinucleotide of the acceptor splice site in a Sicilian subject. Genomics 13: 234-235, 1992. [PubMed: 1577489] [Full Text: https://doi.org/10.1016/0888-7543(92)90232-h]

  931. Rey, K. S., Unger, C. A., Rao, S. P., Miller, S. T. Sickle cell-hemoglobin E disease: clinical findings and implications. J. Pediat. 119: 949-951, 1991. [PubMed: 1960615] [Full Text: https://doi.org/10.1016/s0022-3476(05)83053-7]

  932. Ribeiro, M. L. S., Baysal, E., Kutlar, F., Tamagnini, G. P., Goncalves, P., Lopes, D., Huisman, T. H. J. A novel beta-zero-thalassaemia mutation (codon 15, TGG-to-TGA) is prevalent in a population of central Portugal. Brit. J. Haemat. 80: 567-568, 1992. [PubMed: 1581247] [Full Text: https://doi.org/10.1111/j.1365-2141.1992.tb04581.x]

  933. Ricco, G., Gallo, E., Pich, P. G., Miniero, R., Mazza, U. Haemoglobin G San Jose in an Italian family. Acta Haemat. 52: 180-188, 1974. [PubMed: 4214182] [Full Text: https://doi.org/10.1159/000208238]

  934. Ricco, G., Pich, P. G., Mazza, U., Rossi, G., Ajmar, F., Arese, P., Gallo, E. Hb J Sicilia: beta 65 (E9) lys-to-asn, a beta homologue of the Hb Zambia. FEBS Lett. 39: 200-204, 1974. [PubMed: 4852224] [Full Text: https://doi.org/10.1016/0014-5793(74)80050-5]

  935. Rieder, R. F., Bradley, T. B., Jr. Hemoglobin Gun Hill: an unstable protein associated with chronic hemolysis. Blood 32: 355-369, 1968. [PubMed: 5675976]

  936. Rieder, R. F., Oski, F. A., Clegg, J. B. Hemoglobin Philly (beta 35 tyrosine to phenylalanine): studies in the molecular pathology of hemoglobin. J. Clin. Invest. 48: 1627-1642, 1969. [PubMed: 5822575] [Full Text: https://doi.org/10.1172/JCI106128]

  937. Rieder, R. F., Wolf, D. J., Clegg, J. B., Lee, S. L. Hemoglobin Bushwick, beta 74 (E18) gly-to-val: an unstable hemoglobin found in extremely small amounts. (Abstract) J. Clin. Invest. 53: 65A, 1974.

  938. Rieder, R. F., Zinkham, W. H., Holtzman, N. A. Hemoglobin Zurich: clinical, chemical and kinetic studies. Am. J. Med. 39: 4-20, 1965. [PubMed: 14314237] [Full Text: https://doi.org/10.1016/0002-9343(65)90241-x]

  939. Rihet, P., Flori, L., Tall, F., Traore, A. S., Fumoux, F. Hemoglobin C is associated with reduced Plasmodium falciparum parasitemia and low risk of mild malaria attack. Hum. Molec. Genet. 13: 1-6, 2004. [PubMed: 14613965] [Full Text: https://doi.org/10.1093/hmg/ddh002]

  940. Ringelhann, B., Konotey-Ahulu, F. I. D., Talapatra, N. C., Nkrumah, F. K., Wiltshire, B. G., Lehmann, H. Haemoglobin K Woolwich (beta 132 lysine-to-glutamine) in Ghana. Acta Haemat. 45: 250-258, 1971. [PubMed: 4999133] [Full Text: https://doi.org/10.1159/000208632]

  941. Ristaldi, M. S., Murru, S., Loudianos, G., Casula, L., Porcu, S., Pigheddu, D., Fanni, B., Sciarratta, G. V., Agosti, S., Parodi, M. I., Leone, D., Camaschella, C., Serra, A., Pirastu, M., Cao, A. The C-T substitution in the distal CACCC box of the beta-globin gene promoter is a common cause of silent beta thalassaemia in the Italian population. Brit. J. Haemat. 74: 480-486, 1990. [PubMed: 2346726] [Full Text: https://doi.org/10.1111/j.1365-2141.1990.tb06338.x]

  942. River, G. L., Robbins, A. B., Schwartz, S. O. S-C hemoglobin: a clinical study. Blood 18: 385-416, 1961. [PubMed: 14492555]

  943. Rochette, J., Boissel, J. P., Labie, D., Wajcman, H., Poyart, C., Bohn, B., Varet, B. Polyglobulie par hemoglobine a affinite augmentee: hemoglobine Saint-Jacques beta140 (H18) ala-to-thr, mutant presentant une alteration du site de fixation du 2,3-diphosphoglycerate. Nouv. Rev. Franc. Hemat. 26: 75-77, 1984. [PubMed: 6546989]

  944. Rochette, J., Poyart, C., Varet, B., Wajcman, H. A new hemoglobin variant altering the beta contact: Hb Chemilly beta99 (G1) asp-to-val. FEBS Lett. 166: 8-12, 1984. [PubMed: 6692925] [Full Text: https://doi.org/10.1016/0014-5793(84)80034-4]

  945. Rodrigues de Souza, L., Kimura, E. M., Albuquerque, D. M., Costa, F. F., de Fatima Sonati, M. Hb Osu-Christiansborg (beta-52(D3)asp-to-asn): a de novo mutation in Brazil. Hemoglobin 28: 65-68, 2004. [PubMed: 15008267] [Full Text: https://doi.org/10.1081/hem-120028889]

  946. Rodriguez Romero, W. E., Castillo, M., Chaves, M. A., Saenz, G. F., Gu, L.-H., Wilson, J. B., Baysal, E., Smetanina, N. S., Leonova, J. Y., Huisman, T. H. J. Hb Costa Rica or alpha-2-beta-2-77(EF1)His-to-Arg: the first example of a somatic cell mutation in a globin gene. Hum. Genet. 97: 829-833, 1996. [PubMed: 8641705]

  947. Rohe, R. A., Sharma, V. S., Ranney, H. M. Double heterozygosity for beta thalassemia and hemoglobin D Iran (beta 22 glu-to-gln). (Abstract) Meeting of the American Society of Hematology, Hollywood, Florida, December 1972.

  948. Romain, P. L., Schwartz, A. D., Shamsuddin, M., Adams, J. G., III, Mason, R. G., Vida, L. N., Honig, G. R. Hemoglobin J (Chicago) (beta (E20) ala-to-asp): a new hemoglobin variant resulting from substitution of an external residue. Blood 45: 387-393, 1975. [PubMed: 163659]

  949. Romero, C., Fernandez Fuertes, I., Quintana, A., Blanco, L., Navarro, J. L., Wilson, J. B., Huisman, T. H. J. Hemoglobin G-Szuhu or beta80(EF4)asn-to-lys, in combination with beta-zero-thalassemia in a Spanish family. Hemoglobin 9: 535-539, 1985. [PubMed: 3841346] [Full Text: https://doi.org/10.3109/03630268508997034]

  950. Romero, J. R., Suzuka, S. M., Nagel, R. L., Fabry, M. E. Arginine supplementation of sickle transgenic mice reduces red cell density and Gardos channel activity. Blood 99: 1103-1108, 2002. [PubMed: 11830454] [Full Text: https://doi.org/10.1182/blood.v99.4.1103]

  951. Romey, M.-C., Aguilar-Martinez, P., Demaille, J., Claustres, M. Rapid detection of single nucleotide deletions: application to the beta-6 (-A) mutation of the beta-globin gene and to cystic fibrosis. Hum. Genet. 92: 627-628, 1993. [PubMed: 8262525] [Full Text: https://doi.org/10.1007/BF00420951]

  952. Rooks, H., Bergounioux, J., Game, L., Close, J. P., Osborne, C., Best, S., Senior, T., Height, S., Thompson, R., Hadzic, N., Fraser, P., Bolton-Maggs, P., Thein, S. L. Heterogeneity of the epsilon-gamma-delta-beta-thalassaemias: characterization of three novel English deletions. Brit. J. Haemat. 128: 722-729, 2005. [PubMed: 15725095] [Full Text: https://doi.org/10.1111/j.1365-2141.2005.05368.x]

  953. Ropero, P., Fernandez-Lago, C., Villegas, A., Polo, M., Mateo, M., Mora, A., Gonzalez, F. A. Hb La Coruna (beta-38(C4)thr-to-ile): a new hemoglobin variant leading to familial polycythemia. Hemoglobin 30: 379-383, 2006. [PubMed: 16840229] [Full Text: https://doi.org/10.1080/03630260600755666]

  954. Ropero, P., Villegas, A., Martinez, M., Ataulfo Gonzalez Fernandez, F., Benavente, C., Mateo, M. A deletion of 11 bp (CD 131-134) in exon 3 of the beta-globin gene produces the phenotype of inclusion body beta-thalassemia. Ann. Hemat. 84: 584-587, 2005. [PubMed: 15977037] [Full Text: https://doi.org/10.1007/s00277-004-0992-2]

  955. Rosa, J., Labie, D., Wajcman, H., Boigne, J. M., Cabannes, R., Bierme, R., Ruffie, J. Hemoglobin I Toulouse: beta 66 (E10) lys-to-glu: a new abnormal hemoglobin with a mutation localized on the E10 porphyrin surrounding zone. Nature 223: 190-191, 1969. [PubMed: 5791730] [Full Text: https://doi.org/10.1038/223190a0]

  956. Rosatelli, C., Leoni, G. B., Tuveri, T., Scalas, M. T., Di Tucci, A., Cao, A. Beta-thalassaemia mutations in Sardinians: implications for prenatal diagnosis. J. Med. Genet. 24: 97-100, 1987. [PubMed: 3031299] [Full Text: https://doi.org/10.1136/jmg.24.2.97]

  957. Rosatelli, M. C., Dozy, A., Faa, V., Meloni, A., Sardu, R., Saba, L., Kan, Y. W., Cao, A. Molecular characterization of beta-thalassemia in the Sardinian population. Am. J. Hum. Genet. 50: 422-426, 1992. [PubMed: 1734721]

  958. Rotoli, B., Camera, A., Fontana, R., Frigeri, F., Pandolfi, G., Vecchione, R., Poggi, V., Longo, G., Carestia, C., De Angioletti, M., Lacerra, G., Pucci, P., Marino, G., Ferranti, P., Malorni, A., Romano, R., Formisano, S. Hb-M Hyde Park: a de novo mutation, identified by mass spectrometry and DNA analysis. Haematologica 77: 110-118, 1992. [PubMed: 1398295]

  959. Rouabhi, F., Chardin, P., Boissel, J. P., Beghoul, F., Labie, D., Benabadji, M. Silent beta-thalassemia associated with Hb Knossos beta27(B9) ala-to-ser in Algeria. Hemoglobin 7: 555-561, 1983. [PubMed: 6668188] [Full Text: https://doi.org/10.3109/03630268309027935]

  960. Rousseaux, J., Nuyts, J. P., Demouveau, G., Deutrevaux, M. A severe hemolytic anemia related to a new case of hemoglobin Perth (Abraham Lincoln) in a French patient. Hemoglobin 4: 89-93, 1980. [PubMed: 6153383] [Full Text: https://doi.org/10.3109/03630268009042375]

  961. Rund, D., Cohen, T., Filon, D., Dowling, C. E., Warren, T. C., Barak, I., Rachmilewitz, E., Kazazian, H. H., Jr., Oppenheim, A. Evolution of a genetic disease in an ethnic isolate: beta-thalassemia in the Jews of Kurdistan. Proc. Nat. Acad. Sci. 88: 310-314, 1991. [PubMed: 1986379] [Full Text: https://doi.org/10.1073/pnas.88.1.310]

  962. Rund, D., Dowling, C., Najjar, K., Rachmilewitz, E. A., Kazazian, H. H., Jr., Oppenheim, A. Two mutations in the beta-globin polyadenylation signal reveal extended transcripts and new RNA polyadenylation sites. Proc. Nat. Acad. Sci. 89: 4324-4328, 1992. [PubMed: 1374896] [Full Text: https://doi.org/10.1073/pnas.89.10.4324]

  963. Rund, D., Filon, D., Rachmilewitz, E. A., Cohen, T., Dowling, C., Kazazian, H. H., Oppenheim, A. Molecular analysis of beta-thalassemia in Kurdish Jews: novel mutations and expression studies. (Abstract) Blood 74 (suppl. 1): 220a, 1989.

  964. Ruvidic, R., Efremov, G. D., Juricic, D., Rolovic, Z., Pendic, S. Hemoglobin Beograd (alpha (2)-beta (2) 121 glu-to-val) interacting with beta-thalassemia. Acta Haemat. 54: 180-187, 1975. [PubMed: 809962] [Full Text: https://doi.org/10.1159/000208070]

  965. Ryrie, D. R., Plowman, D., Lehmann, H. Haemoglobin Sherwood Forest (beta 104 (G6) arg-to-thr). FEBS Lett. 83: 260-262, 1977. [PubMed: 590504] [Full Text: https://doi.org/10.1016/0014-5793(77)81018-1]

  966. Saba, L., Meloni, A., Sardu, R., Travi, M., Primignani, P., Rosatelli, M. C., Cao, A. A novel beta-thalassemia mutation (G-to-A) at the initiation codon of the beta-globin gene. Hum. Mutat. 1: 420-422, 1992. [PubMed: 1301952] [Full Text: https://doi.org/10.1002/humu.1380010512]

  967. Saenz, G. F., Arroyo, G., Montero, G., Lima, F., Martinez, G., Elizondo, J., Jimenez, J. Two cases of hemoglobin New York in Costa Rica. Hemoglobin 4: 101-105, 1980. [PubMed: 7353956] [Full Text: https://doi.org/10.3109/03630268009042377]

  968. Saglio, G., Camaschella, C., Serra, A., Bertero, T., Cambrin, G. R., Guerrasio, A., Mazza, U., Izzo, P., Terragni, F., Giglioni, B., Comi, P., Ottolenghi, S. Italian type of deletional hereditary persistence of fetal hemoglobin. Blood 68: 646-651, 1986. [PubMed: 2427137]

  969. Saiki, R. K., Bugawan, T. L., Horn, G. T., Mullis, K. B., Erlich, H. A. Analysis of enzymatically amplified beta-globin and HLA-DQ-alpha DNA with allele-specific oligonucleotide probes. Nature 324: 163-166, 1986. [PubMed: 3785382] [Full Text: https://doi.org/10.1038/324163a0]

  970. Salhany, J. M. The deoxygenation kinetics of hemoglobin Rainier (beta 145 tyr-to-cys). Biochem. Biophys. Res. Commun. 47: 784-789, 1972. [PubMed: 5026295] [Full Text: https://doi.org/10.1016/0006-291x(72)90560-8]

  971. Salomon, H., Tatarski, I., Dance, N., Huehns, E. R., Shooter, E. M. A new hemoglobin variant found in a Bedouin tribe: hemoglobin 'Rambam'. Isr. J. Med. Sci. 1: 836-840, 1965. [PubMed: 5856126]

  972. Salzano, A. M., Carbone, V., Pagano, L., Buffardi, S., De Rosa, C., Pucci, P. Hb Vila Real (beta-36(C2)pro-to-his) in Italy: characterization of the amino acid substitution and the DNA mutation. Hemoglobin 26: 21-31, 2002. [PubMed: 11939509] [Full Text: https://doi.org/10.1081/hem-120002937]

  973. Salzano, F. M. Permanence or change? The meaning of genetic variation. Proc. Nat. Acad. Sci. 97: 5317-5321, 2000. [PubMed: 10805790] [Full Text: https://doi.org/10.1073/pnas.97.10.5317]

  974. Sammarco, P., Giambona, A., Lo Gioco, P., Di Marzo, R., Maggio, A. Evidence of the African origin of sickle cell hemoglobin in Western Sicily. Hemoglobin 12: 193-196, 1988. [PubMed: 2898460] [Full Text: https://doi.org/10.3109/03630268808998026]

  975. Sanders-Haigh, L., Anderson, W. F., Francke, U. The beta-globin gene is on the short arm of human chromosome 11. Nature 283: 683-686, 1980. [PubMed: 7354859] [Full Text: https://doi.org/10.1038/283683a0]

  976. Sansone, G., Carrell, R. W., Lehmann, H. Haemoglobin Genova: beta 28 (B10) leucine to proline. Nature 214: 877-879, 1967. [PubMed: 6054966] [Full Text: https://doi.org/10.1038/214877a0]

  977. Sansone, G., Sciarratta, G. V., Genova, R., Darbre, P. D., Lehmann, H. Haemoglobin Shepherds Bush (beta 74(E18) gly-to-asp) in an Italian family. Acta Haemat. 57: 102-108, 1977. [PubMed: 402764] [Full Text: https://doi.org/10.1159/000207866]

  978. Sathiapalan, R., Robinson, M. G. Hereditary haemolytic anaemia due to an abnormal haemoglobin (haemoglobin Kings County). Brit. J. Haemat. 15: 579-587, 1968. [PubMed: 5710064] [Full Text: https://doi.org/10.1111/j.1365-2141.1968.tb01580.x]

  979. Schiliro, G., Li Volti, S., Musumeci, S., Mollica, F., Marinucci, M., Mavilio, L., Tentori, L. Sicily: a cluster of Hb G-San Jose. Hemoglobin 5: 725-730, 1981. [PubMed: 7338474] [Full Text: https://doi.org/10.3109/03630268108991840]

  980. Schiliro, G., Musumeci, S., Russo, A., Marino, S., Russo, G., Marinucci, M., Fontanarosa, P. P., Tentori, L. Hemoglobin G Copenhagen beta 47 (CD6) asp-to-asn in a Sicilian family. Hemoglobin 5: 195-198, 1981. [PubMed: 7216819] [Full Text: https://doi.org/10.3109/03630268108996925]

  981. Schiliro, G., Russo-Mancuso, G., Dibenedetto, S. P., Samperi, P., Di Cataldo, A., Ragusa, R., Testa, R. Six rare hemoglobin variants found in Sicily. Hemoglobin 15: 431-437, 1991. [PubMed: 1802885] [Full Text: https://doi.org/10.3109/03630269108998862]

  982. Schmidt, R. M., Bechtel, K. C., Johnson, M. H., Therrell, B. L., Jr., Moo-Penn, W. F. Hemoglobin Lufkin: beta 29 (B11) gly-to-asp an unusual hemoglobin variant involving an internal amino acid residue. Hemoglobin 1: 799-814, 1977. [PubMed: 24022] [Full Text: https://doi.org/10.3109/03630267709003908]

  983. Schmidt, R. M., Jue, D. L., Lyonnais, J., Moo-Penn, W. F. Hemoglobin (Bethesda), beta 145 (HC2) tyr-to-his, in a Canadian family. Am. J. Clin. Path. 66: 449-452, 1976. [PubMed: 949044] [Full Text: https://doi.org/10.1093/ajcp/66.2.449]

  984. Schnee, J., Aulehla-Scholz, C., Eigel, A., Horst, J. Hb D Los Angeles (D-Punjab) and Hb Presbyterian: analysis of the defect at the DNA level. Hum. Genet. 84: 365-367, 1990. [PubMed: 2307460] [Full Text: https://doi.org/10.1007/BF00196236]

  985. Schnee, J., Griese, E. U., Eigel, A., Horst, J. Beta-thalassemia gene analysis in a Turkish family reveals a 7 bp deletion in the coding region. (Letter) Blood 73: 2224-2225, 1989. [PubMed: 2730955]

  986. Schneider, R. G., Alperin, J. B., Brimhall, B., Jones, R. T. Hemoglobin P (beta 117 arg): structure and properties. J. Lab. Clin. Med. 73: 616-622, 1969. [PubMed: 5775133]

  987. Schneider, R. G., Bremner, J. E., Brimhall, B., Jones, R. T., Shih, T.-B. Hemoglobin Cowtown (beta 146 HC3 his-to-leu): a mutant with high oxygen affinity and erythrocytosis. Am. J. Clin. Path. 72: 1028-1032, 1979. [PubMed: 42311] [Full Text: https://doi.org/10.1093/ajcp/72.6.1028]

  988. Schneider, R. G., Haggard, M. E., McNutt, C. W., Johnson, J. E., Bowman, B. H., Barnett, D. R. Hemoglobin G Coushatta: a new variant in an American Indian family. Science 143: 697-698, 1964. [PubMed: 14081243] [Full Text: https://doi.org/10.1126/science.143.3607.697]

  989. Schneider, R. G., Hethig, R. A., Bilunos, M., Brimhall, B. Hemoglobin Baylor (beta 81 leu-to-arg), an unstable mutant with high oxygen affinity. Hemoglobin 1: 85-96, 1977.

  990. Schneider, R. G., Hosty, T. S., Tomlin, G., Atkins, R., Brimhall, B., Jones, R. T. Hb Mobile beta 73(E17) asp-to-val: a new variant. Biochem. Genet. 13: 411-415, 1975. [PubMed: 1180880] [Full Text: https://doi.org/10.1007/BF00485784]

  991. Schneider, R. G., Ueda, S., Alperin, J. B., Brimhall, B., Jones, R. T. Hemoglobin Sabine at beta 91 (E7) leu-to-pro: an unstable variant causing severe anemia with inclusion bodies. New Eng. J. Med. 280: 739-745, 1969. [PubMed: 5773354] [Full Text: https://doi.org/10.1056/NEJM196904032801402]

  992. Schneider, R. G., Ueda, S., Alperin, J. B., Levin, W. C., Jones, R. T., Brimhall, B. Hemoglobin D Los Angeles in two Caucasian families: hemoglobin SD disease and hemoglobin D thalassemia. Blood 32: 250-259, 1968. [PubMed: 5672850]

  993. Schneider, R. Personal Communication. Galveston, Tex. 10/6/1978.

  994. Schoenfelder, S., Sexton, T., Chakalova, L., Cope, N. F., Horton, A., Andrews, S., Kurukuti, S., Mitchell, J. A., Umlauf, D., Dimitrova, D. S., Eskiw, C. H., Luo, Y., Wei, C.-L., Ruan, Y., Bieker, J. J., Fraser, P. Preferential associations between co-regulated genes reveal a transcription interactome in erythroid cells. Nature Genet. 42: 53-61, 2010. [PubMed: 20010836] [Full Text: https://doi.org/10.1038/ng.496]

  995. Schroeder, W. A., Jones, R. T. Some aspects of the chemistry and function of human and animal hemoglobins. Fortschr. Chem. Organ. Naturst. 23: 113-194, 1965.

  996. Schroeder, W. A., Powars, D., Shelton, J. B., Shelton, J. R., Wilson, J. B., Huisman, T. H. J., Bedros, A. A. An unusual phenotypic expression of Hb-Leiden. Biochem. Genet. 20: 1175-1187, 1982. [PubMed: 7165693] [Full Text: https://doi.org/10.1007/BF00498941]

  997. Schwartz, H. C., Spaet, T. H., Zuelzer, W. W., Neel, J. V., Robinson, A. R., Kaufman, S. F. Combinations of hemoglobin G, hemoglobin S and thalassemia occurring in one family. Blood 12: 238-250, 1957. [PubMed: 13403987]

  998. Sciarratta, G. V., Ivaldi, G., Moruzzi, F. Hb J-Guantanamo in a Chilean baby. Hemoglobin 14: 115-117, 1990. [PubMed: 2384311] [Full Text: https://doi.org/10.3109/03630269009002260]

  999. Sciarratta, G. V., Ivaldi, G., Sansone, G., Wilson, J. B., Webber, B. B., Huisman, T. H. J. Hb Volga or beta27(B9)ala-to-asp in an Italian family. Hemoglobin 9: 91-93, 1985. [PubMed: 3838977] [Full Text: https://doi.org/10.3109/03630268508996988]

  1000. Sciarratta, G. V., Ivaldi, G. Hb Matera (beta55(D6)met-to-lys): a new unstable hemoglobin variant in an Italian family. Hemoglobin 14: 79-85, 1990. [PubMed: 2384314] [Full Text: https://doi.org/10.3109/03630269009002256]

  1001. Scott, A. F., Phillips, J. A., III, Migeon, B. R. DNA restriction endonuclease analysis for localization of human beta- and delta-globin genes on chromosome 11. Proc. Nat. Acad. Sci. 76: 4563-4565, 1979. [PubMed: 291988] [Full Text: https://doi.org/10.1073/pnas.76.9.4563]

  1002. Seid-Akhavan, M., Ayres, M., Salzano, F. M., Winter, W. P., Rucknagel, D. L. Two more examples of Hb Porto Alegre, beta 9 ser-to-cys, in Belem, Brazil. Hum. Hered. 23: 175-181, 1973. [PubMed: 4756855] [Full Text: https://doi.org/10.1159/000152570]

  1003. Serjeant, B., Myerscough, E., Serjeant, G. R., Higgs, D. R., Moo-Penn, W. F. Sickle cell-hemoglobin D Iran: a benign sickle cell syndrome. Hemoglobin 6: 57-59, 1982. [PubMed: 7073867] [Full Text: https://doi.org/10.3109/03630268208996934]

  1004. Serjeant, G. R., Higgs, D. R., Hambleton, I. R. Elderly survivors with homozygous sickle cell disease. (Letter) New Eng. J. Med. 356: 642-643, 2007. [PubMed: 17287491] [Full Text: https://doi.org/10.1056/NEJMc066547]

  1005. Serjeant, G. R., Richards, R., Barbor, P. R. H., Milner, P. F. Relatively benign sickle-cell anaemia in 60 patients aged over 30 in the West Indies. Brit. Med. J. 3: 86-91, 1968. [PubMed: 4232783] [Full Text: https://doi.org/10.1136/bmj.3.5610.86]

  1006. Shaeffer, J. R., Schmidt, G. J., Kingston, R. E., Bunn, H. F. Synthesis of hemoglobin Cranston, an elongated beta chain variant. J. Molec. Biol. 140: 377-389, 1980. [PubMed: 7441747] [Full Text: https://doi.org/10.1016/0022-2836(80)90390-3]

  1007. Shah, S. C., Malone, J. I., Boissel, J.-P., Kasper, T. J. Hemoglobin South Florida: new variant with normal electrophoretic pattern mistaken for glycosylated hemoglobin. Diabetes 35: 1073-1076, 1986. [PubMed: 3758492] [Full Text: https://doi.org/10.2337/diab.35.10.1073]

  1008. Shalev, O., Boylen, A. L., Levene, C., Oppenheim, A., Rachmilewitz, E. A. Sickle cell trait in a white Jewish family presenting as splenic infarction at high altitude. Am. J. Hemat. 27: 46-48, 1988. [PubMed: 3354556] [Full Text: https://doi.org/10.1002/ajh.2830270111]

  1009. Sherman, I. J. The sickling phenomenon, with special reference to the difference of sickle cell anemia from the sickle cell trait. Bull. Johns Hopkins Hosp. 67: 309-324, 1940.

  1010. Shibata, S., Iuchi, I., Hamilton, H. B. The first instance of hemoglobin E in a Japanese family. Proc. Jpn. Acad. 40: 846-851, 1962.

  1011. Shibata, S., Iuchi, I., Mazagi, T., Takeda, I. Hemoglobinopathy in Japan. Bull. Yamaguchi Med. Sch. 10: 1-9, 1963.

  1012. Shibata, S., Iuchi, I., Miyaji, T., Ueda, S., Yamashita, K., Suzuno, R. A case of hemolytic disease associated with the production of Heinz bodies and of an abnormal hemoglobin (Hb Ube-1). Med. Biol. 59: 79-84, 1961.

  1013. Shibata, S., Iuchi, I., Miyaji, T., Ueda, S. Spectroscopic characterization of hemoglobin M (Iwate) and hemoglobin M (Kurume), the two variants of hemoglobin M found in Japan. Acta Haemat. Jpn. 24: 477-485, 1961. [PubMed: 13911805]

  1014. Shibata, S., Iuchi, I., Miyaji, T. Hemoglobin M disease in Japan. Isr. J. Med. Sci. 1: 766-768, 1965. [PubMed: 5856115]

  1015. Shibata, S., Iuchi, I. Hemoglobin-Hikari (alpha-2-beta-2, T-7): a fast-moving hemoglobin demonstrated in two families of Japanese people, with a brief note on the abnormal hemoglobins of Japan which are likely to be confused with it. (Abstract) Proceedings of the 9th Congress of the International Society of Hematology, Mexico City 1962. Pp. 65-70.

  1016. Shibata, S., Miyaji, T., Iuchi, I., Ohba, Y., Yamamoto, K. Amino acid substitution in hemoglobin M (Akita). J. Biochem. 63: 193-198, 1968. [PubMed: 5669922] [Full Text: https://doi.org/10.1093/oxfordjournals.jbchem.a128761]

  1017. Shibata, S., Miyaji, T., Iuchi, I., Ueda, S., Takeda, I. Hemoglobin Hikari (beta 61 asn): a fast-moving hemoglobin found in two unrelated Japanese families. Clin. Chim. Acta 10: 101-105, 1964. [PubMed: 14203236] [Full Text: https://doi.org/10.1016/0009-8981(64)90153-6]

  1018. Shibata, S., Miyaji, T., Iuchi, I., Ueda, S. A comparative study of hemoglobin M (Iwate) and hemoglobin M (Kurume) by means of electrophoresis, chromatography and analysis of peptide chains. Acta Haemat. Jpn. 24: 486-494, 1961. [PubMed: 13911808]

  1019. Shibata, S., Miyaji, T., Ohba, Y. Abnormal hemoglobins in Japan. Hemoglobin 4: 395-408, 1980. [PubMed: 6998928] [Full Text: https://doi.org/10.3109/03630268008996220]

  1020. Shibata, S., Miyaji, T., Ueda, S., Matsvoka, M., Iuchi, I., Yamada, K., Shinkai, N. Hemoglobin Tochigi (beta 56-59 deleted). A new unstable hemoglobin discovered in a Japanese family. Proc. Jpn. Acad. 46: 440-445, 1970.

  1021. Shih, D. T., Jones, R. T., Shih, M. F.-C., Jones, M. B., Koler, R. D., Howard, J. Hemoglobin Chico (beta66 (E10) lys-to-thr): a new variant with decreased oxygen affinity. Hemoglobin 11: 453-464, 1987. [PubMed: 3429244] [Full Text: https://doi.org/10.3109/03630268708998005]

  1022. Shih, M.-C., Wu, K.-H., Liu, S.-C., Chang, J.-G. Hb Tak: A beta chain elongation at the end of the beta chain, in a Taiwanese. Hemoglobin 29: 65-67, 2005. [PubMed: 15768557]

  1023. Shimizu, K., Keino, H., Takenaka, O. Hemoglobin Lufkin (beta-29[B11]gly-to-asp) found in a Japanese. Hemoglobin 12: 81-85, 1988. [PubMed: 3384703] [Full Text: https://doi.org/10.3109/03630268808996887]

  1024. Shulman, L. N., Bunn, H. F. Hb Deer Lodge in a Caucasian American: effect of iron deficiency on level of variant. Hemoglobin 12: 197-199, 1988. [PubMed: 3384712] [Full Text: https://doi.org/10.3109/03630268808998027]

  1025. Sick, K., Beale, D., Irvine, D., Lehmann, H., Goodall, P. T., MacDougall, S. Hemoglobin G (Copenhagen) and hemoglobin J (Cambridge): two new beta-chain variants of hemoglobin A. Biochim. Biophys. Acta 140: 231-242, 1967. [PubMed: 6048303] [Full Text: https://doi.org/10.1016/0005-2795(67)90463-1]

  1026. Sierakowska, H., Sambade, M. J., Agrawal, S., Kole, R. Repair of thalassemic human beta-globin mRNA in mammalian cells by antisense oligonucleotides. Proc. Nat. Acad. Sci. 93: 12840-12844, 1996. [PubMed: 8917506] [Full Text: https://doi.org/10.1073/pnas.93.23.12840]

  1027. Silvestroni, E., Bianco, I., Brancati, C. Haemoglobin P in a family of southern Italian extraction. Nature 200: 658-659, 1963. [PubMed: 14109943] [Full Text: https://doi.org/10.1038/200658a0]

  1028. Simonis, M., Klous, P., Splinter, E., Moshkin, Y., Willemsen, R., de Wit, E., van Steensel, B., de Laat, W. Nuclear organization of active and inactive chromatin domains conserved by chromosome conformation capture-on-chip (4C). Nature Genet. 38: 1348-1354, 2006. [PubMed: 17033623] [Full Text: https://doi.org/10.1038/ng1896]

  1029. Smetanina, N. S., Gu, L.-H., Rodriguez Romero, W. E., Howard, E. F., Huisman, T. H. J. The relative levels of different types of beta-mRNA and beta-globin in BFU-E derived colonies from patients with beta-chain variants: further evidence for somatic mosaicism in the Hb Costa Rica carrier (beta-77(EF1) his-arg). Hemoglobin 20: 199-212, 1996. [PubMed: 8854130] [Full Text: https://doi.org/10.3109/03630269609027929]

  1030. Smith, E. W., Conley, C. L. Sickle cell-hemoglobin D disease. Ann. Intern. Med. 50: 94-98, 1959. [PubMed: 13617832] [Full Text: https://doi.org/10.7326/0003-4819-50-1-94]

  1031. Smith, E. W., Krevans, J. R. Clinical manifestations of hemoglobin C disorders. Bull. Johns Hopkins Hosp. 104: 17-43, 1959. [PubMed: 13618691]

  1032. So, C.-C., Ma, S.-K., Law, K.-M., Chan, A. Y.-Y., Chan, L.-C., Wong, K.-F. Hb Kodaira II: a high oxygen affinity variant with a novel mutation in the beta-globin gene and phenotypic identity to Hb Kodaira. Hemoglobin 26: 205-207, 2002. [PubMed: 12144067] [Full Text: https://doi.org/10.1081/hem-120005462]

  1033. Somjee, S., Yu, L. C., Hagar, A. F., Hempe, J. M. Diagnosis and characterization of Hb C/Hb Iowa: a rare but easily misidentified compound heterozygous condition. Hemoglobin 28: 7-13, 2004. [PubMed: 15008260] [Full Text: https://doi.org/10.1081/hem-120028882]

  1034. Spivak, V. A., Molchanova, T. P., Postnikov, Y. V., Aseeva, E. A., Lutsenko, I. N., Tokarev, Y. N. A new abnormal hemoglobin: Hb Mozhaisk beta92 (F8) his-to-arg. Hemoglobin 6: 169-181, 1982. [PubMed: 7096107] [Full Text: https://doi.org/10.3109/03630268209002292]

  1035. Spivak, V. A. Letter to the editor. (Letter) Hemoglobin 13: 219-220, 1989. [PubMed: 2737920] [Full Text: https://doi.org/10.3109/03630268908998077]

  1036. Spritz, R. A., Jagadeeswaran, P., Choudary, P. V., Biro, P. A., Elder, J. T., deRiel, J. K., Manley, J. L., Gefter, M. L., Forget, B. G., Weissman, S. M. Base substitution in an intervening sequence of a beta-plus-thalassemic human globin gene. Proc. Nat. Acad. Sci. 78: 2455-2459, 1981. [PubMed: 6264477] [Full Text: https://doi.org/10.1073/pnas.78.4.2455]

  1037. Spritz, R. A. Duplication-deletion polymorphism 5-prime to the human beta-globin gene. Nucleic Acids Res. 9: 5037-5047, 1981. [PubMed: 7312624] [Full Text: https://doi.org/10.1093/nar/9.19.5037]

  1038. Stabler, S. P., Jones, R. T., Head, C., Shih, D. T.-B., Fairbanks, V. F. Hemoglobin Denver (beta-41 (C7) phe-to-ser): a low-O(2)-affinity variant associated with chronic cyanosis and anemia. Mayo Clin. Proc. 69: 237-243, 1994. [PubMed: 8133661] [Full Text: https://doi.org/10.1016/s0025-6196(12)61062-3]

  1039. Stamatoyannopoulos, G., Nute, P. E., Adamson, J. W., Bellingham, A. J., Funk, D. Hemoglobin Olympia (beta 20 valine-to-methionine): an electrophoretically silent variant associated with high oxygen affinity and erythrocytosis. J. Clin. Invest. 52: 342-349, 1973. [PubMed: 4683875] [Full Text: https://doi.org/10.1172/JCI107190]

  1040. Stamatoyannopoulos, G., Nute, P. E., Giblett, E., Detter, J., Chard, R. Haemoglobin M Hyde Park occurring as a fresh mutation: diagnostic, structural, and genetic considerations. J. Med. Genet. 13: 142-147, 1976. [PubMed: 933112] [Full Text: https://doi.org/10.1136/jmg.13.2.142]

  1041. Stamatoyannopoulos, G., Parer, J. T., Finch, C. A. Physiologic implications of a hemoglobin with decreased oxygen affinity (hemoglobin Seattle). New Eng. J. Med. 281: 915-919, 1969. [PubMed: 5811424] [Full Text: https://doi.org/10.1056/NEJM196910232811701]

  1042. Stamatoyannopoulos, G., Woodson, R., Papayannopoulou, T., Heywood, D., Kurachi, S. Inclusion-body beta-thalassemia trait: a form of beta-thalassemia producing clinical manifestations in simple heterozygotes. New Eng. J. Med. 290: 939-943, 1974. [PubMed: 4361439] [Full Text: https://doi.org/10.1056/NEJM197404252901705]

  1043. Stamatoyannopoulos, G., Yoshida, A., Adamson, J., Heinenberg, S. Hemoglobin Rainier (beta 145 tyrosine to histidine): alkali-resistant hemoglobin with increased oxygen affinity. Science 159: 741-743, 1968. [PubMed: 17795074] [Full Text: https://doi.org/10.1126/science.159.3816.741]

  1044. Stamatoyannopoulos, G., Yoshida, A. Single chain alkali resistance in hemoglobin Rainier: beta 145 tyrosine to histidine. Science 166: 1005-1006, 1969. [PubMed: 5347519] [Full Text: https://doi.org/10.1126/science.166.3908.1005]

  1045. Steadman, J. H., Yates, A., Huehns, E. R. Idiopathic Heinz body anaemia: Hb Bristol (beta 67 (E 11) val-to-asp). Brit. J. Haemat. 18: 435-446, 1970. [PubMed: 5420592] [Full Text: https://doi.org/10.1111/j.1365-2141.1970.tb01457.x]

  1046. Steger, H., Eigel, A., Flatz, G., Horst, J. Hemoglobin E and codon 17 nonsense: two beta-globin gene mutations common in Southeast Asia detected by the use of ARMS. Ann. Hemat. 67: 119-120, 1993. [PubMed: 8373896] [Full Text: https://doi.org/10.1007/BF01701733]

  1047. Steinberg, M. H., Adams, J. G., III, Morrison, W. T., Pullen, D. J., Abney, R., Ibrahim, A., Rieder, R. F. Hemoglobin Mississippi (beta-44 ser-to-cys): studies of the thalassemic phenotype in a mixed heterozygote with beta-plus-thalassemia. J. Clin. Invest. 79: 826-832, 1987. [PubMed: 2434529] [Full Text: https://doi.org/10.1172/JCI112890]

  1048. Steinberg, M. H., Adams, J. G., III. Thalassemia: recent insights into molecular mechanisms. Am. J. Hemat. 12: 81-92, 1982. [PubMed: 6278929] [Full Text: https://doi.org/10.1002/ajh.2830120113]

  1049. Steinberg, M. H., Adams, J. G., Thigpen, J. T., Morrison, F. S., Dreiling, J. Hemoglobin Hope (beta 136 gly-to-asp)-S disease: clinical and biochemical studies. J. Lab. Clin. Med. 84: 632-642, 1974. [PubMed: 4283785]

  1050. Steinberg, M. H., Lovell, W. J., Coleman, M., Dreiling, B. J., Adams, J. G. Hemoglobin Hope: studies of oxygen equilibrium in heterozygotes, hemoglobin S-Hope disease, and isolated hemoglobin Hope. J. Lab. Clin. Med. 88: 125-131, 1976. [PubMed: 932531]

  1051. Stinson, R. A. Isoelectric focusing studies of a stable asymmetrical hybrid formed with a new hemoglobin variant Hemoglobin Alberta. J. Lab. Clin. Med. 90: 623-631, 1977. [PubMed: 903694]

  1052. Stinson, R. A. Asymmetric hybrids formed with hemoglobin British Columbia (beta 101 glu-to-lys). Hemoglobin 8: 483-496, 1984. [PubMed: 6500987] [Full Text: https://doi.org/10.3109/03630268408991733]

  1053. Stout, C., Holland, C. K., Bird, R. M. Hemoglobin D in an Oklahoma family. Arch. Intern. Med. 114: 296-300, 1964. [PubMed: 14160125] [Full Text: https://doi.org/10.1001/archinte.1964.03860080146016]

  1054. Strahler, J. R., Rosenbloom, B. B., Hanash, S. M. A silent, neutral substitution detected by reverse-phase high-performance liquid chromatography: hemoglobin Beirut. Science 221: 860-862, 1983. [PubMed: 6879181] [Full Text: https://doi.org/10.1126/science.6879181]

  1055. Studencki, A. B., Conner, B. J., Impraim, C. C., Teplitz, R. L., Wallace, R. B. Discrimination among the human beta-A, beta-S, and beta-C-globin genes using allele-specific oligonucleotide hybridization probes. Am. J. Hum. Genet. 37: 42-51, 1985. [PubMed: 2983543]

  1056. Sugihara, J., Imamura, T., Nagafuchi, S., Bonaventura, J., Bonaventura, C., Cashon, R. Hemoglobin Rahere, a human hemoglobin variant with amino acid substitution at the 2,3-diphosphoglycerate binding site: functional consequences of the alteration and effects of bezafibrate on the oxygen bindings. J. Clin. Invest. 76: 1169-1173, 1985. [PubMed: 3930571] [Full Text: https://doi.org/10.1172/JCI112072]

  1057. Suryantoro, P., Takeshima, Y., Haryanto, A., Matsuo, M. C to T transition at the first nucleotide of codon 63 of the beta-globin gene corresponding to hemoglobin M-Saskatoon in an Indonesian boy. Jpn. J. Hum. Genet. 40: 195-201, 1995. [PubMed: 7663000] [Full Text: https://doi.org/10.1007/BF01883577]

  1058. Suzuki, Y., Shimizu, T., Sakai, H., Tamaki, M., Koizumi, K., Kuriyama, T., Tsuchida, E., Koseki, H., Shirasawa, T. Model mice for Presbyterian hemoglobinopathy (asn(beta108)-to-lys) confer hemolytic anemia with altered oxygen affinity and instability of Hb. Biochem. Biophys. Res. Commun. 295: 869-876, 2002. [PubMed: 12127975] [Full Text: https://doi.org/10.1016/s0006-291x(02)00752-0]

  1059. Sydenstricker, V. P., Horton, B., Payne, R. A., Huisman, T. H. J. Studies on a fast hemoglobin variant found in a Negro family in association with thalassemia. Clin. Chim. Acta 6: 677-685, 1961.

  1060. Tagawa, Y., Fujinami, S., Kadota, Y., Nakagawa, T., Seki, T., Shiozaki, Y., Inoue, K., Harano, T., Harano, K., Ueda, S. Hb Olomouc [beta86(F2)ala-to-asp] found in a Japanese family. Hemoglobin 16: 73-76, 1992. [PubMed: 1634364] [Full Text: https://doi.org/10.3109/03630269209005678]

  1061. Taketa, F., Huang, Y. P., Libnoch, J. A., Dessel, B. H. Hemoglobin Wood beta 97 (FG4) his-to-leu: a new high-oxygen-affinity hemoglobin associated with familial erythrocytosis. Biochim. Biophys. Acta 400: 348-353, 1975. [PubMed: 1164511]

  1062. Takihara, Y., Nakamura, T., Yamada, H., Takagi, Y., Fukumaki, Y. A novel mutation in the TATA box in a Japanese patient with beta-plus-thalassemia. Blood 67: 547-550, 1986. [PubMed: 3002527]

  1063. Talbot, D., Collis, P., Antoniou, M., Vidal, M., Grosveld, F., Greaves, D. R. A dominant control region from the human beta-globin locus conferring integration site-independent gene expression. Nature 338: 352-355, 1989. [PubMed: 2922063] [Full Text: https://doi.org/10.1038/338352a0]

  1064. Tamagnini, G. P., Lopes, M. C., Castanheira, M. E., Wainscoat, J. S., Wood, W. G. Beta-plus-thalassaemia--Portuguese type: clinical, haematological and molecular studies of a newly defined form of beta-thalassaemia. Brit. J. Haemat. 54: 189-200, 1983. [PubMed: 6189507] [Full Text: https://doi.org/10.1111/j.1365-2141.1983.tb02087.x]

  1065. Tamagnini, G. P., Ribeiro, M. L., Valente, V., Ramachandran, M., Wilson, J. B., Baysal, E., Gu, L.-H., Huisman, T. H. J. Hb Coimbra or beta-99(G1)asp-to-glu, a newly discovered high oxygen affinity variant. Hemoglobin 15: 487-496, 1991. [PubMed: 1814856] [Full Text: https://doi.org/10.3109/03630269109027896]

  1066. Tanaka, Y., Kelleher, J. F., Schwartz, E., Asakura, T. Oxygen binding and stability properties of Hb Santa Ana (beta88 leu-to-pro). Hemoglobin 9: 157-169, 1985. [PubMed: 3839771] [Full Text: https://doi.org/10.3109/03630268508996997]

  1067. Tatsis, B., Sofroniadou, K., Stergiopoulos, K. Hemoglobin Pyrgos (beta 83 gly-to-asp): a new hemoglobin variant. (Abstract) Meeting of the American Society of Hematology, Hollywood, Florida, December 1972.

  1068. Taylor, J. M., Dozy, A. M., Kan, Y. W., Vermus, H. E., Lie-Injo, L. E., Ganesan, J., Todd, D. Genetic lesion in homozygous thalassaemia (hydrops fetalis). Nature 251: 392-393, 1974. [PubMed: 4424635] [Full Text: https://doi.org/10.1038/251392a0]

  1069. Teixeira, A., Tahiri-Alaoui, A., West, S., Thomas, B., Ramadass, A., Martianov, I., Dye, M., James, W., Proudfoot, N. J., Akoulitchev, A. Autocatalytic RNA cleavage in the human beta-globin pre-mRNA promotes transcription termination. Nature 432: 526-530, 2004. [PubMed: 15565159] [Full Text: https://doi.org/10.1038/nature03032]

  1070. Tentori, L., Carta Sorcini, M., Buccella, C. Hemoglobin Abruzzo: beta 143 (H 21) his to arg. Clin. Chim. Acta 38: 258-262, 1972. [PubMed: 5031790] [Full Text: https://doi.org/10.1016/0009-8981(72)90241-0]

  1071. Tentori, L. Three examples of double heterozygosis for beta-thalassemia and a rare hemoglobin variant. (Abstract) International Symposium of Hemoglobins and Thalassemia, Istanbul, Turkey 1974.

  1072. Thein, S. L., Best, S., Sharpe, J., Paul, B., Clark, D. J., Brown, M. J. Hemoglobin Chesterfield (beta-28 leu-to-arg) produces the phenotype of inclusion body beta thalassemia. (Letter) Blood 77: 2791-2793, 1991. [PubMed: 1675132]

  1073. Thein, S. L., Hesketh, C., Taylor, P., Temperley, I. J., Hutchinson, R. M., Old, J. M., Wood, W. G., Clegg, J. B., Weatherall, D. J. Molecular basis for dominantly inherited inclusion body beta-thalassemia. Proc. Nat. Acad. Sci. 87: 3924-3928, 1990. [PubMed: 1971109] [Full Text: https://doi.org/10.1073/pnas.87.10.3924]

  1074. Thein, S. L., Hesketh, C., Weatherall, D. J. The molecular basis of beta-thalassemia in UK Asian Indians: applications to prenatal diagnosis. Brit. J. Haemat. 70: 225-231, 1988. [PubMed: 2903765] [Full Text: https://doi.org/10.1111/j.1365-2141.1988.tb02468.x]

  1075. Thein, S. L., Lynch, J. R., Old, J. M., Weatherall, D. J. Direct detection of haemoglobin E with MnlI. J. Med. Genet. 24: 110-112, 1987. [PubMed: 3031297] [Full Text: https://doi.org/10.1136/jmg.24.2.110]

  1076. Thillet, J., Blouquit, Y., Garel, M. C., Dreyfus, B., Reyes, F., Cohen-Solal, M., Beuzard, Y., Rosa, J. Hemoglobin Creteil beta 89 (F5) ser-to-asn: high oxygen affinity variant of hemoglobin frozen in a quaternary R-structure. J. Molec. Med. 1: 135-150, 1976.

  1077. Thillet, J., Cohen-Solal, M., Seligmann, M., Rosa, J. Functional and physiochemical studies of hemoglobin St. Louis beta 28 (B10) leu-to-gln: a variant with ferric beta heme iron. J. Clin. Invest. 58: 1098-1106, 1976. [PubMed: 186485] [Full Text: https://doi.org/10.1172/JCI108561]

  1078. Thuret, I., Bardakdjian, J., Badens, C., Wajcman, H., Galacteros, F., Vanuxem, D., Perrimond, H., Giraud, F., Lena-Russo, D. Priapism following splenectomy in an unstable hemoglobin: hemoglobin Olmsted beta-141(H19)leu-to-arg. Am. J. Hemat. 51: 133-136, 1996. [PubMed: 8579053] [Full Text: https://doi.org/10.1002/(SICI)1096-8652(199602)51:2<133::AID-AJH6>3.0.CO;2-Z]

  1079. Tilghman, S. M., Curtis, P. J., Tiemeier, D. C., Leder, P., Weissmann, C. The intervening sequence of a mouse beta-globin gene is transcribed within the 15S beta-globin mRNA precursor. Proc. Nat. Acad. Sci. 75: 1309-1313, 1978. [PubMed: 274720] [Full Text: https://doi.org/10.1073/pnas.75.3.1309]

  1080. Todd, D., Chan, V., Schneider, R. G., Dozy, A. M., Kan, Y. W., Chan, T. K. Globin chain synthesis in haemoglobin New York (beta 113 valine-to-glutamic acid). Brit. J. Haemat. 46: 557-564, 1980. [PubMed: 7437334] [Full Text: https://doi.org/10.1111/j.1365-2141.1980.tb06012.x]

  1081. Tondo, C. V., Salzano, F. M., Rucknagel, D. L. Hemoglobin Porto Alegre, a possible polymer of normal hemoglobin in a Caucasian Brazilian family. Am. J. Hum. Genet. 15: 265-279, 1963. [PubMed: 13985474]

  1082. Tondo, C. V. Asymmetric tetramer in a second occurrence of hemoglobin Porto Alegre beta 9 ser-to-cys. Hemoglobin 1: 195-210, 1976. [PubMed: 1052181] [Full Text: https://doi.org/10.3109/03630267608991680]

  1083. Tonz, O., Winterhalter, K. H., Glatthaar, B. E. New mutation leading to beta-thalassaemia minor. Nature N.B. 241: 127-128, 1973. [PubMed: 4512457] [Full Text: https://doi.org/10.1038/newbio241127a0]

  1084. Townes, T. M., Behringer, R. R. Human globin locus activation region (LAR): role in temporal control. Trends Genet. 6: 219-223, 1990. [PubMed: 2202110] [Full Text: https://doi.org/10.1016/0168-9525(90)90182-6]

  1085. Trabuchet, G., Elion, J., Dunda, O., Lapoumeroulie, C., Ducrocq, R., Nadifi, S., Zohoun, I., Chaventre, A., Carnevale, P., Nagel, R. L., Krishnamoorthy, R., Labie, D. Nucleotide sequence evidence of the unicentric origin of the beta-C mutation in Africa. Hum. Genet. 87: 597-601, 1991. [PubMed: 1680789] [Full Text: https://doi.org/10.1007/BF00209020]

  1086. Traeger-Synodinos, J., Kanavakis, E., Vrettou, C., Maragoudaki, E., Michael, T. H., Metaxotou-Mavromati, A., Kattamis, C. The triplicated alpha-globin gene locus in beta-thalassemia heterozygotes: clinical, haematological, biosynthetic and molecular studies. Brit. J. Haemat. 95: 467-471, 1996. [PubMed: 8943886] [Full Text: https://doi.org/10.1046/j.1365-2141.1996.d01-1939.x]

  1087. Traeger-Synodinos, J., Tzetis, M., Kanavakis, E., Metaxotou-Mavromati, A., Kattamis, C. The Corfu delta-beta-thalassaemia mutation in Greece: haematological phenotype and prevalence. Brit. J. Haemat. 79: 302-305, 1991. [PubMed: 1720325] [Full Text: https://doi.org/10.1111/j.1365-2141.1991.tb04537.x]

  1088. Trecartin, R. F., Liebhaber, S. A., Chang, J. C., Lee, Y. W., Kan, Y. W. Beta-zero-thalassemia in Sardinia is caused by a nonsense mutation. J. Clin. Invest. 68: 1012-1017, 1981. [PubMed: 6457059] [Full Text: https://doi.org/10.1172/jci110323]

  1089. Treisman, R., Proudfoot, N. J., Shander, M., Maniatis, T. A single base change at a splice site in a beta-0-thalassemia gene causes abnormal RNA splicing. Cell 29: 903-911, 1982. [PubMed: 7151176] [Full Text: https://doi.org/10.1016/0092-8674(82)90452-4]

  1090. Trent, R. J., Harris, M. G., Fleming, P. J., Wyatt, K., Hughes, W. G., Kronenberg, H. Haemoglobin D Punjab: interaction with alpha thalassaemia and diagnosis by gene mapping. Scand. J. Haemat. 32: 275-282, 1984. [PubMed: 6322284] [Full Text: https://doi.org/10.1111/j.1600-0609.1984.tb01693.x]

  1091. Tsoi, W. C., Li, C. K., Plaseka-Karanfilska, D., Efremov, G. D. Hb Brockton (beta-138(H16)ala-to-pro) observed in a Chinese boy. Hemoglobin 22: 397-400, 1998. [PubMed: 9730372] [Full Text: https://doi.org/10.3109/03630269809071536]

  1092. Tuan, D., Solomon, W., Li, Q., London, I. M. The 'beta-like globin' gene domain in human erythroid cells. Proc. Nat. Acad. Sci. 82: 6384-6388, 1985. [PubMed: 3879975] [Full Text: https://doi.org/10.1073/pnas.82.19.6384]

  1093. Tuchinda, S., Beale, D., Lehmann, H. A new haemoglobin in a Thai family: a case of haemoglobin Siriraj-beta thalassaemia. Brit. Med. J. 1: 1583-1585, 1965. [PubMed: 14288126] [Full Text: https://doi.org/10.1136/bmj.1.5450.1583]

  1094. Turhan, A., Weiss, L. A., Mohandas, N., Coller, B. S., Frenette, P. S. Primary role for adherent leukocytes in sickle cell vascular occlusion: a new paradigm. Proc. Nat. Acad. Sci. 99: 3047-3051, 2002. [PubMed: 11880644] [Full Text: https://doi.org/10.1073/pnas.052522799]

  1095. Turner, J. W., Jr., Jones, R. T., Brimhall, B., DuVal, M. C., Koler, R. D. Characterization of hemoglobin Burke (beta 107 (G9) gly-to-arg). Biochem. Genet. 14: 577-585, 1976. [PubMed: 10883] [Full Text: https://doi.org/10.1007/BF00485836]

  1096. Ulukutlu, L., Ozsahin, H., Wilson, J. B., Webber, B. B., Hu, H., Kutlar, A., Kutlar, F., Huisman, T. H. J. HB Brockton (beta138(H16)ala-to-pro) observed in a Turkish girl. Hemoglobin 13: 509-513, 1989. [PubMed: 2599887] [Full Text: https://doi.org/10.3109/03630268908998091]

  1097. van den Berg, H. M., Bruin, M. C. A., Batelaan, D., van Delft, P., van Zwieten, R., Roos, D., Harteveld, C. L., Bernini, L. F., Giordano, P. C. Hb Nijkerk: a new mutation at codons 138/139 of the beta-globin gene inducing severe hemolytic anemia in a Dutch girl. Hemoglobin 23: 135-144, 1999. [PubMed: 10335981] [Full Text: https://doi.org/10.3109/03630269908996158]

  1098. Vassilopoulos, G., Papassotiriou, I., Voskaridou, E., Stamoulakatou, A., Premetis, E., Kister, J., Marden, M., Griffon, N., Poyart, C., Wajcman, H., Galacteros, F., Loukopoulos, D. Hb Arta [beta45(CD4)phe-to-cys]: a new unstable haemoglobin with reduced oxygen affinity in trans with beta-thalassaemia. Brit. J. Haemat. 91: 595-601, 1995. [PubMed: 8555060] [Full Text: https://doi.org/10.1111/j.1365-2141.1995.tb05353.x]

  1099. Vella, F., Beale, D., Lehmann, H. Haemoglobin O Arab in Sudanese. Nature 209: 308-309, 1966. [PubMed: 5915974] [Full Text: https://doi.org/10.1038/209308a0]

  1100. Vella, F., Isaacs, W. A., Lehmann, H. Hemoglobin G (Saskatoon): beta-22-glu-ala. Canad. J. Biochem. 45: 351-353, 1967. [PubMed: 6021187] [Full Text: https://doi.org/10.1139/o67-041]

  1101. Vella, F., Lorkin, P. A., Carrell, R. W. A new hemoglobin variant resembling hemoglobin E: hemoglobin E(Saskatoon): beta-22 glu replaced by lys. Canad. J. Biochem. 45: 1385-1391, 1967. [PubMed: 6048388] [Full Text: https://doi.org/10.1139/o67-163]

  1102. Ventruto, V., Baglioni, C., De Rosa, L., Bianchi, P., Colombo, B., Quattrin, N. Haemoglobin Caserta: an abnormal haemoglobin observed in a southern Italian family. Scand. J. Haemat. 2: 118-125, 1965. [PubMed: 14343423] [Full Text: https://doi.org/10.1111/j.1600-0609.1965.tb01287.x]

  1103. Verma, C., Edwards, J. H. Linkage data for the beta-hemoglobin locus. Cytogenet. Cell Genet. 22: 646, 1978. [PubMed: 752559] [Full Text: https://doi.org/10.1159/000131043]

  1104. Vidaud, M., Gattoni, R., Stevenin, J., Vidaud, D., Amselem, S., Chibani, J., Rosa, J., Goossens, M. A 5-prime splice-region G-to-C mutation in exon 1 of the human beta-globin gene inhibits pre-mRNA splicing: a mechanism for beta(+)-thalassemia. Proc. Nat. Acad. Sci. 86: 1041-1045, 1989. [PubMed: 2915972] [Full Text: https://doi.org/10.1073/pnas.86.3.1041]

  1105. Villegas, A., Malcorra, J. J., Balda, I., Calero, F., Porres, A., Alvarez-Sala, J. L., Espinos, D. A new Spanish family with Hb Louisville. Am. J. Med. Genet. 32: 9-14, 1989. [PubMed: 2705488] [Full Text: https://doi.org/10.1002/ajmg.1320320103]

  1106. Villegas, A., Martin, G., Wilson, J. B., Webber, B. B., Hu, H., Kutlar, A., Kutlar, F., Huisman, T. H. J. HB Extremadura or beta133(H11)val-to-leu, a new mildly unstable hemoglobin in a Spanish female. Hemoglobin 13: 505-508, 1989. [PubMed: 2599886] [Full Text: https://doi.org/10.3109/03630268908998090]

  1107. Villegas, A., Perez-Clausell, C., Sanchez, J., Sal del Rio, E. A new case of thalassemia intermedia: interaction of a triplicated alpha-globin locus and beta-thalassemia trait. Hemoglobin 16: 99-101, 1992. [PubMed: 1634369] [Full Text: https://doi.org/10.3109/03630269209005683]

  1108. Villegas, A., Ropero, P., Nogales, A., Gonzalez, F. A., Mateo, M., Mazo, E., Rodrigo, E., Arias, M. Hb Santander [beta-34(B16)val-to-asp (GTC-GAC)]: a new unstable variant found as a de novo mutation in a Spanish patient. Hemoglobin 27: 31-35, 2003. [PubMed: 12603091] [Full Text: https://doi.org/10.1081/hem-120016378]

  1109. Villegas, A., Wilson, J. B., Chen, S. S., Calero, F., Reinares, L., Huisman, T. H. J., Espinos, D. Haemoglobin Presbyterian (beta 108 (G10) asn-to-lys) in a Spanish family. Acta Haemat. 76: 161-163, 1986. [PubMed: 3101357] [Full Text: https://doi.org/10.1159/000206043]

  1110. Virshup, D. M., Zinkham, W. H., Sirota, R. L., Caughey, W. S. Unique sensitivity of Hb Zurich to oxidative injury by phenazopyridine: reversal of the effects by elevating carboxyhemoglobin levels in vivo and in vitro. Am. J. Hemat. 14: 315-324, 1983. [PubMed: 6859031] [Full Text: https://doi.org/10.1002/ajh.2830140402]

  1111. Wada, Y., Ikkala, E., Imai, K., Matsuo, T., Matsuda, H., Lehtinen, M., Hayashi, A., Lehmann, H. Structure and function of a new hemoglobin variant, Hb Meilahti (beta36 (C2) pro-to-thr), characterized by mass spectrometry. Acta Haemat. 78: 109-113, 1987. [PubMed: 3120455] [Full Text: https://doi.org/10.1159/000205856]

  1112. Wade Cohen, P. T., Yates, A., Bellingham, A. J., Huehns, E. R. Amino-acid substitution in the alpha-1-beta-1 intersubunit contact of haemoglobin-Camden (beta 131 (H9) gln-to-glu). (Letter) Nature 243: 467-468, 1973.

  1113. Wade, P. T., Jenkins, T., Huehns, E. R. Haemoglobin variant in a Bushman: haemoglobin D beta-Bushman (16 gly to arg). Nature 216: 688-690, 1967. [PubMed: 6082467] [Full Text: https://doi.org/10.1038/216688b0]

  1114. Wajcman, H., Aguilar i Bascompte, J. L., Labie, D., Poyart, C., Bohn, B. Structural and functional studies of hemoglobin Barcelona (beta94 asp-to-his). J. Molec. Biol. 156: 185-202, 1982. [PubMed: 7097767] [Full Text: https://doi.org/10.1016/0022-2836(82)90466-1]

  1115. Wajcman, H., Amegnizin, K. P. E., Belkhodja, O., Labie, D., Kernemp, R. Hemoglobin J (Lome) (beta 59 (E3) lys-to-asn): a new fast moving variant found in a Togolese. FEBS Lett. 84: 372-374, 1977. [PubMed: 598514] [Full Text: https://doi.org/10.1016/0014-5793(77)80727-8]

  1116. Wajcman, H., Baudin-Chich, V., Kister, J., Feo, C., Gombaud-Saintonge, G., Bohn, B., Marden, M., Pagnier, J., Poyart, C., Dode, C., Galacteros, F., Blouquit, Y., Cynober, T., Tchernia, G. Hemoglobin J Guantanamo (beta128 (H6) ala-to-asp) in association with hemoglobin C and alpha-thalassemia in a family from Benin. Am. J. Hemat. 28: 170-175, 1988. [PubMed: 2841847] [Full Text: https://doi.org/10.1002/ajh.2830280308]

  1117. Wajcman, H., Blouquit, Y., Vasseur, C., Le Querrec, A., Laniece, M., Melevendi, C., Rasore, A., Galacteros, F. Two new human hemoglobin variants caused by unusual mutational events: Hb Zaire contains a five residue repetition within the alpha-chain and Hb Duino has two residues substituted in the beta-chain. Hum. Genet. 89: 676-680, 1992. [PubMed: 1511986] [Full Text: https://doi.org/10.1007/BF00221961]

  1118. Wajcman, H., Drupt, F., Henthorn, J. S., Kister, J., Prehu, C., Riou, J., Prome, D., Galacteros, F. Two new variants with the same substitution at position beta-122: Hb Bushey [beta-122(GH5)phe-to-leu] and Hb Casablanca [beta-65(E9)lys-to-met; beta-122(GH5)phe-to-leu]. Hemoglobin 24: 125-132, 2000. [PubMed: 10870883] [Full Text: https://doi.org/10.3109/03630260009003431]

  1119. Wajcman, H., Girodon, E., Prome, D., North, M. L., Plassa, F., Duwig, I., Kister, J., Bergerat, J. P., Oberling, F., Lampert, E., Lonsdorfer, J., Goossens, M., Galacteros, F. Germline mosaicism for an alanine to valine substitution at residue beta 140 in hemoglobin Puttelange, a new variant with oxygen affinity. Hum. Genet. 96: 711-716, 1995. [PubMed: 8522332] [Full Text: https://doi.org/10.1007/BF00210304]

  1120. Wajcman, H., Kilmartin, J. V., Najman, A., Labie, D. Hemoglobin Cochin-Port-Royal: consequences of the replacement of the beta chain C-terminal by an arginine. Biochim. Biophys. Acta 400: 354-364, 1975. [PubMed: 240418] [Full Text: https://doi.org/10.1016/0005-2795(75)90191-9]

  1121. Wajcman, H., Kister, J., M'Rad, A., Prome, D., Milpied, N., Rapp, M. J., Harousseau, J. L., Riou, J., Bardakdjian, J., Galacteros, F. Hb Saint Nazaire (beta-103[G5]phe-to-ile): a new example of polycythemia due to a hemoglobin variant with increased oxygen affinity. Am. J. Hemat. 44: 16-21, 1993. [PubMed: 8342560] [Full Text: https://doi.org/10.1002/ajh.2830440105]

  1122. Wajcman, H., Kister, J., Marden, M., Bohn, B., Blouquit, Y., Descamps, J., Goudemand, M., Poyart, C., Galacteros, F. Hemoglobin Calais (beta76 (E20) ala-to-pro): a hemoglobin variant with decreased intrinsic oxygen affinity. Biochim. Biophys. Acta 1096: 60-66, 1991.

  1123. Wajcman, H., Kister, J., Prehu, C., Riou, J., Godart, C., Bardakdjian, J., Soummer, A. M., Prome, D., Galacteros, F. Hb Tende [beta-124(H2)pro to leu]: a new variant with a moderate increase in oxygen affinity. Hemoglobin 22: 517-523, 1998. [PubMed: 9859935] [Full Text: https://doi.org/10.3109/03630269809071549]

  1124. Wajcman, H., Kister, J., Prome, D., Galacteros, F., Gilsanz, F. Hb Villaverde [beta-89 (F5) ser-to-thr]: the structural modification of an intrasubunit contact is responsible for a high oxygen affinity. Biochim. Biophys. Acta 1225: 89-94, 1993. [PubMed: 8241293] [Full Text: https://doi.org/10.1016/0925-4439(93)90127-m]

  1125. Wajcman, H., Kister, J., Vasseur, C., Blouquit, Y., Trastour, J. C., Cottenceau, D., Galacteros, F. Structure of the EF corner favors deamidation of asparaginyl residues in hemoglobin: the example of Hb La Roche-sur-Yon [beta 81(EF5)leu to his]. Biochim. Biophys. Acta 1138: 127-132, 1992. [PubMed: 1540659] [Full Text: https://doi.org/10.1016/0925-4439(92)90052-o]

  1126. Wajcman, H., Krishnamoorthy, R., Gacon, G., Elion, J., Allard, C., Labie, D. A new hemoglobin variant involving the distal histidine: Hb Bicetre (beta 63(E7) his-to-pro). J. Molec. Med. 1: 187-197, 1976.

  1127. Wajcman, H., Labie, D., Schapira, G. Hemoglobin Tours: thr beta-87 (F3) deleted and hemoglobin St. Antoine: gly-to-leu beta-74-75 (E18-19) deleted: consequences for oxygen affinity and protein stability. Biochim. Biophys. Acta 295: 495-504, 1973. [PubMed: 4699574]

  1128. Wajcman, H., Lahary, A., Prome, D., Kister, J., Riou, J., Godart, C., Prehu, C., Traeger-Synodinos, J., Papassotiriou, I., Galacteros, F. Hb Mont Saint Aignan (beta-128(H6)ala-to-pro): a new unstable variant leading to chronic microcytic anemia. Hemoglobin 25: 57-65, 2001. [PubMed: 11300350] [Full Text: https://doi.org/10.1081/hem-100103070]

  1129. Wajcman, H., Mrad, A., Blouquit, Y., Parmentier, C., Riou, J., Galacteros, F. Hemoglobin Villejuif (beta123(H1)thr-to-ile): a new variant found in coincidence with polycythemia vera. Am. J. Hemat. 32: 294-297, 1989. [PubMed: 2816924] [Full Text: https://doi.org/10.1002/ajh.2830320410]

  1130. Wajcman, H., Riou, J., Prome, D., Kister, J., Galacteros, F. Hb Brie Comte Robert (beta-36(C2)pro-to-ala): a new hemoglobin variant with high oxygen affinity and marked hydrophobic properties. Hemoglobin 23: 281-286, 1999. [PubMed: 10490142] [Full Text: https://doi.org/10.3109/03630269909005710]

  1131. Wajcman, H., Vasseur, C., Blouquit, Y., Santo, D. E., Peres, M. J., Martins, M. C., Poyart, C., Galacteros, F. Hemoglobin Redondo [beta 92(F8) his-to-asn]: an unstable hemoglobin variant associated with heme loss which occurs in two forms. Am. J. Hemat. 38: 194-200, 1991. [PubMed: 1951318] [Full Text: https://doi.org/10.1002/ajh.2830380308]

  1132. Walker, L., McFarlane, A., Patterson, M., Eng, B., Waye, J. S. Hb Castilla [beta-32(B14)leu-to-arg] caused by a de novo mutation. Hemoglobin 27: 253-256, 2003. [PubMed: 14649317] [Full Text: https://doi.org/10.1081/hem-120026051]

  1133. Watson-Williams, E. J., Beale, D., Irvine, D., Lehmann, H. A new haemoglobin, D Ibadan (beta-87 threonine-to-lysine), producing no sickle-cell haemoglobin D disease with haemoglobin S. Nature 205: 1273-1279, 1965. [PubMed: 14311973] [Full Text: https://doi.org/10.1038/2051273a0]

  1134. Waye, J. S., Eng, B., Patterson, M., Chui, D. H. K., Fernandes, B. J. Novel beta-0-thalassemia mutation in a Canadian woman of British descent (codons 72/73, -AGTGA, +T). Hemoglobin 21: 385-387, 1997. [PubMed: 9255617] [Full Text: https://doi.org/10.3109/03630269709000671]

  1135. Waye, J. S., Eng, B., Patterson, M., Chui, D. H. K., Fernandes, B. J. Novel beta-thalassemia mutation in patients of Jewish descent: [beta-30(B12)arg-to-gly or IVS-1(-2)(A-to-G)] Hemoglobin 22: 83-85, 1998. [PubMed: 9494053] [Full Text: https://doi.org/10.3109/03630269809071522]

  1136. Waye, J. S., Walker, L., Lafferty, J., Lemire, E. G., Chui, D. H. K. Dominant beta-thalassemia due to a newly identified frameshift mutation in exon 3 (codon 113, GTG to TG). Hemoglobin 26: 83-86, 2002. [PubMed: 11939518] [Full Text: https://doi.org/10.1081/hem-120002945]

  1137. Weatherall, D., Clegg, J. The Thalassemia Syndromes. (4th ed.) Oxford: Blackwell Science (pub.) 2001.

  1138. Weatherall, D. J., Clegg, J. B., Collender, S. T., Wells, R. G. M., Gale, R. E., Huehns, E. R., Perutz, M. F., Viggiano, G., Ho, C. Haemoglobin Radcliffe (beta 99 (G1) ala): a high oxygen-affinity variant causing familial polycythaemia. Brit. J. Haemat. 35: 177-191, 1977. [PubMed: 857849] [Full Text: https://doi.org/10.1111/j.1365-2141.1977.tb00575.x]

  1139. Weatherall, D. J., Clegg, J. B., Knox-Macaulay, H. H. M., Bunch, C., Hopkins, C. R., Temperley, I. J. A genetically determined disorder with features both of thalassaemia and congenital dyserythropoietic anaemia. Brit. J. Haemat. 24: 681-702, 1973. [PubMed: 4351905] [Full Text: https://doi.org/10.1111/j.1365-2141.1973.tb01696.x]

  1140. Weatherall, D. J., Clegg, J. B. The Thalassaemia Syndromes. Oxford: Blackwell (pub.) 1981.

  1141. Weatherall, D. J. Hemoglobin J (Baltimore) coexisting in a family with hemoglobin S-I. Bull. Johns Hopkins Hosp. 114: 1-12, 1964. [PubMed: 14117783]

  1142. Weatherall, D. J. The inherited diseases of hemoglobin are an emerging global health burden. Blood 115: 4331-4336, 2010. [PubMed: 20233970] [Full Text: https://doi.org/10.1182/blood-2010-01-251348]

  1143. Weaver, G. A., Rahbar, S., Ellsworth, C. A., de Alarcon, P. A., Forbes, G. B., Beutler, E. Iron overload in three generations of a family with hemoglobin Olympia. Gastroenterology 87: 695-702, 1984. [PubMed: 6745619]

  1144. Weinstein, B. I., White, J. M., Wiltshire, A., Lehmann, H. Hemoglobina Buenos Aires: una nueva hemoglobina inestable. (Abstract) Medicina 32: 749, 1973.

  1145. Welch, S. G., Bateman, C. Hb D-Neath or beta121 (GH4) glu-to-ala: a new member of the Hb D family. Hemoglobin 17: 255-259, 1993. [PubMed: 8330979] [Full Text: https://doi.org/10.3109/03630269308998901]

  1146. Welch, S. G. Haemoglobin G-Szuhu beta 80 asn-to-lys in an English family. Humangenetik 28: 331-334, 1975. [PubMed: 1176123] [Full Text: https://doi.org/10.1007/BF00284807]

  1147. Went, L. N., MacIver, J. E. Sickle-cell haemoglobin-J disease. Brit. Med. J. 2: 138-139, 1959. [PubMed: 13843994] [Full Text: https://doi.org/10.1136/bmj.2.5144.138]

  1148. Westaway, D., Williamson, R. An intron nucleotide sequence variant in a cloned beta-plus-thalassemia globin gene. Nucleic Acids Res. 9: 1777-1788, 1981. [PubMed: 6264391] [Full Text: https://doi.org/10.1093/nar/9.8.1777]

  1149. White, J. M., Brain, M. C., Lorkin, P. A., Lehmann, H., Smith, M. Mild 'unstable haemoglobin haemolytic anaemia' caused by haemoglobin Shepherds Bush (beta 74 (E18) gly to asp). Nature 225: 939-941, 1970. [PubMed: 5415129] [Full Text: https://doi.org/10.1038/225939a0]

  1150. White, J. M., Szur, L., Gillies, I. D. S., Lorkin, P. A., Lehmann, H. Familial polycythaemia caused by a new haemoglobin variant: Hb Heathrow, beta 103 (G5) phenylalanine to leucine. Brit. Med. J. 3: 665-667, 1973. [PubMed: 4742453] [Full Text: https://doi.org/10.1136/bmj.3.5882.665]

  1151. Wiedermann, B. F., Indrak, K., Wilson, J. B., Webber, B. B., Yang, K. G., Kutlar, F., Kutlar, A., Huisman, T. H. J. Hb Saint Louis or beta 28 (B10) leu-to-gln in a Czechoslovakian male. Hemoglobin 10: 673-676, 1986. [PubMed: 3557999] [Full Text: https://doi.org/10.3109/03630268609036572]

  1152. Wilkinson, T., Brennan, S. O., Carrell, R. W., Wells, R. M., Como, P., Kronenberg, H. Hemoglobin Summer Hill beta 52(D3) asp-to-his: a new variant from Sydney, Australia. Hemoglobin 4: 185-193, 1980. [PubMed: 7190137] [Full Text: https://doi.org/10.3109/03630268009042385]

  1153. Wilkinson, T., Chua, C. G., Carrell, R. W., Robin, H., Exner, T., Lee, K. M., Kronenberg, H. A new haemoglobin variant, haemoglobin Camperdown (beta 104 (G6) arginine-to-serine), which has normal physiological function. Biochim. Biophys. Acta 393: 195-200, 1975. [PubMed: 1138922] [Full Text: https://doi.org/10.1016/0005-2795(75)90231-7]

  1154. Wilkinson, T., Como, P., Brock, P., Kronenberg, H., Trent, R. J. A., Brennan, S. O. Hemoglobin I High Wycombe in an Australian family. Hemoglobin 11: 51-53, 1987. [PubMed: 3583766] [Full Text: https://doi.org/10.3109/03630268709036583]

  1155. Wilkinson, T., Kronenberg, H., Isaacs, W. A., Lehmann, H. Haemoglobin J Baltimore interacting with beta-thalassaemia in an Australian family. Med. J. Aust. 1: 907-910, 1967. [PubMed: 6026391] [Full Text: https://doi.org/10.5694/j.1326-5377.1967.tb21727.x]

  1156. Williamson, D., Beresford, C. H., Langdown, J. V., Anderson, C. C., Green, A. R. Polycythaemia associated with homozygosity for the abnormal haemoglobin Sherwood Forest (beta104 (G6)arg-to-thr). Brit. J. Haemat. 86: 890-892, 1994. [PubMed: 7918091] [Full Text: https://doi.org/10.1111/j.1365-2141.1994.tb04852.x]

  1157. Williamson, D., Brennan, S. O., Carrell, R. W. Hb Brisbane (beta68 (E12) leu-to-his) is unstable. Hemoglobin 7: 473-475, 1983. [PubMed: 6629830] [Full Text: https://doi.org/10.3109/03630268309038418]

  1158. Williamson, D., Brennan, S. O., Muir, H., Carrell, R. W. Hemoglobin Collingwood beta60 (E4) val-to-ala--a new unstable hemoglobin. Hemoglobin 7: 511-519, 1983. [PubMed: 6421773] [Full Text: https://doi.org/10.3109/03630268309027932]

  1159. Williamson, D., Nutkins, J., Rosthoj, S., Brennan, S. O., Williams, D. H., Carrell, R. W. Characterization of Hb Aalborg, a new unstable hemoglobin variant, by fast atom bombardment mass spectrometry. Hemoglobin 14: 137-145, 1990. [PubMed: 2272837] [Full Text: https://doi.org/10.3109/03630269009046955]

  1160. Williamson, D., Perry, D. J., Brown, K., Langdown, J. V., de Silva, C. Compound heterozygosity for two beta chain variants: Hb S (beta6(A3)glu--val) and the high affinity variant Hb San Diego (beta109(G11)val--met). Hemoglobin 19: 27-32, 1995. [PubMed: 7615400] [Full Text: https://doi.org/10.3109/03630269509069727]

  1161. Williamson, D., Wells, R. M. G., Anderson, R., Matthews, J. A new unstable and low oxygen affinity hemoglobin variant: Hb J-Auckland (beta25 (B7) gly-to-asp). Hemoglobin 11: 221-230, 1987. [PubMed: 3654265] [Full Text: https://doi.org/10.3109/03630268709017888]

  1162. Williamson, R., Eskdale, J., Coleman, D. V., Niazi, M., Loeffler, F. E., Modell, B. M. Direct gene analysis of chorionic villi: a possible technique for first-trimester antenatal diagnosis of haemoglobinopathies. Lancet 318: 1125-1127, 1981. Note: Originally Volume II. [PubMed: 6118574] [Full Text: https://doi.org/10.1016/s0140-6736(81)90583-3]

  1163. Wilson, C. I. D., Cave, R. J., Lehmann, H., Close, M., Imai, K. Haemoglobin Warwickshire (beta5 (A2) pro-to-arg): a possible 'fine tuning' of 2,3-DPG affinity by beta5 pro (FEBS 1918). FEBS Lett. 176: 331-333, 1984. [PubMed: 6548451] [Full Text: https://doi.org/10.1016/0014-5793(84)81190-4]

  1164. Wilson, G., Forrest, P., Heppinstall, S., Green, B. N., Goodeve, A. C., Peake, I. R., Reilly, J. T., Porter, N., Rees, D. C. A second case of Hb Renert [beta-133(H11)val-ala]. Hemoglobin 25: 337-340, 2001. [PubMed: 11570728] [Full Text: https://doi.org/10.1081/hem-100105228]

  1165. Wilson, J. B., Lam, H., Williams, D., Huisman, T. H. J. Hemoglobin G-San Jose beta 7 (A4) glu-to-gly in a Mexican family. Hemoglobin 4: 95-99, 1980. [PubMed: 7353959] [Full Text: https://doi.org/10.3109/03630268009042376]

  1166. Wilson, J. B., Ramachandran, M., Webber, B. B., Kutlar, F., Hazelwood, L. F., Barnett, D., Hirschler, N. V., Huisman, T. H. J. Hb Cleveland or alpha(2)beta(2)93(F9)cys-to-arg; 121(GH4)glu-to-gln. Hemoglobin 15: 269-278, 1991. [PubMed: 1787096] [Full Text: https://doi.org/10.3109/03630269109027879]

  1167. Wilson, J. B., Webber, B. B., Hu, H., Kutlar, A., Kutlar, F., Codrington, J. F., Prchal, J. T., Hall, K. M., de Pablos, J. M., Rodriguez, I., Huisman, T. H. J. Hemoglobin Birmingham and hemoglobin Galicia: two unstable beta chain variants characterized by small deletions and insertions. Blood 75: 1883-1887, 1990. [PubMed: 2158827]

  1168. Wilson, J. T., Forget, B. G., Wilson, L. B., Weissman, S. M. Human globin messenger RNA: importance of cloning for structural analysis. Science 196: 200-202, 1977. [PubMed: 847468] [Full Text: https://doi.org/10.1126/science.847468]

  1169. Wilson, J. T., Milner, P. F., Summer, M. E., Nallaseth, F. S., Fadel, H. E., Reindollar, R. H., McDonough, P. G., Wilson, L. B. Use of restriction endonucleases for mapping the allele for beta-S-globin. Proc. Nat. Acad. Sci. 79: 3628-3631, 1982. [PubMed: 6285354] [Full Text: https://doi.org/10.1073/pnas.79.11.3628]

  1170. Winslow, R. M., Charache, S. Hemoglobin Richmond: subunit dissociation and oxygen equilibrium properties. J. Biol. Chem. 250: 6939-6942, 1975. [PubMed: 239952]

  1171. Winslow, R. M., Swenberg, M.-L., Gross, E., Chervenick, P., Buchman, R. R., Anderson, W. F. Hemoglobin McKees Rocks (beta 145 tyr-to-term), a human 'nonsense' mutation leading to a shortened beta chain. (Abstract) Am. J. Hum. Genet. 27: 95A, 1975.

  1172. Witkowska, H. E., Lubin, B. H., Beuzard, Y., Baruchel, S., Esseltine, D. W., Vichinsky, E. P., Kleman, K. M., Bardakdjian-Michau, J., Pinkoski, L., Cahn, S., Roitman, E., Green, B. N., Falick, A. M., Shackleton, C. H. L. Sickle cell disease in a patient with sickle cell trait and compound heterozygosity for hemoglobin S and hemoglobin Quebec-Chori. New Eng. J. Med. 325: 1150-1154, 1991. [PubMed: 1891024] [Full Text: https://doi.org/10.1056/NEJM199110173251607]

  1173. Witkowski, J. A. The 51 most-cited articles in the Cold Spring Harbor Symposia on Quantitative Biology. Curr. Contents 33(28): 7-16, 1990.

  1174. Wong, C., Antonarakis, S. E., Goff, S. C., Orkin, S. H., Boehm, C. D., Kazazian, H. H., Jr. On the origin and spread of beta-thalassemia: recurrent observation of four mutations in different ethnic groups. Proc. Nat. Acad. Sci. 83: 6529-6532, 1986. [PubMed: 3462712] [Full Text: https://doi.org/10.1073/pnas.83.17.6529]

  1175. Wong, C., Antonarakis, S. E., Goff, S. C., Orkin, S. H., Forget, B. G., Nathan, D. G., Giardina, P. J. V., Kazazian, H. H., Jr. Beta-thalassemia due to two novel nucleotide substitutions in consensus acceptor splice sequences of the beta-globin gene. Blood 73: 914-918, 1989. [PubMed: 2920213]

  1176. Wong, C., Dowling, C. E., Saiki, R. K., Higuchi, R. G., Erlich, H. A., Kazazian, H. H., Jr. Characterization of beta-thalassaemia mutations using direct genomic sequencing of amplified single copy DNA. Nature 330: 384-386, 1987. [PubMed: 3683554] [Full Text: https://doi.org/10.1038/330384a0]

  1177. Wong, S. C., Ali, M. A. M., Lam, H., Webber, B. B., Wilson, J. B., Huisman, T. H. J. Hemoglobin Hamilton or beta11(A8)val-to-ile: a silent beta-chain variant detected by triton X-100 acid-urea polyacrylamide gel electrophoresis. Am. J. Hemat. 16: 47-52, 1984. [PubMed: 6695908] [Full Text: https://doi.org/10.1002/ajh.2830160106]

  1178. Wong, S. C., Ali, M. A. M., Nicholson, W., Wilson, J. B., Lam, H., Huisman, T. H. J. A second patient with hemoglobin Alberta, a high-oxygen-affinity variant causing erythrocytosis and forming asymmetric tetramers. Hemoglobin 2: 557-559, 1978. [PubMed: 750556] [Full Text: https://doi.org/10.3109/03630267809005357]

  1179. Wong, S. C., Bouver, N., Wilson, J. B., Huisman, T. H. J. Hb J Georgia = Hb J Baltimore = beta16 gly-to-asp. Clin. Chim. Acta 35: 521-522, 1971. [PubMed: 5125343] [Full Text: https://doi.org/10.1016/0009-8981(71)90235-x]

  1180. Wood, E. T., Stover, D. A., Slatkin, M., Nachman, M. W., Hammer, M. F. The beta-globin recombinational hotspot reduces the effects of strong selection around the HbC, a recently arisen mutation providing resistance to malaria. Am. J. Hum. Genet. 77: 637-642, 2005. [PubMed: 16175509] [Full Text: https://doi.org/10.1086/491748]

  1181. Woodson, R. D., Heywood, J. D., Lenfant, C. Oxygen transport in hemoglobin San Francisco. Clin. Res. 18: 134, 1970.

  1182. Worthington, S., Lehmann, H. The first observation of Hb D Punjab beta(0) thalassaemia in an English family with 22 cases of unsuspected beta(0) thalassaemia minor among its members. J. Med. Genet. 22: 377-381, 1985. [PubMed: 4078867] [Full Text: https://doi.org/10.1136/jmg.22.5.377]

  1183. Yamada, H., Hotta, H., Ohba, Y., Miyaji, T., Ito, J., Minami, M. Hemoglobin Pyrgos (beta 83 gly-to-asp) in a Japanese family. Hemoglobin 1: 245-256, 1977. [PubMed: 893127] [Full Text: https://doi.org/10.3109/03630267709003407]

  1184. Yamagishi, Y., Ikeda, K., Takahara, J., Irino, S., Hasui, H., Fujiwara, T., Kaji, Y., Harano, T., Harano, K. Hb J-Guantanamo [beta-128(H6)ala-to-asp] found in a Japanese family. Hemoglobin 17: 379-385, 1993. [PubMed: 8226098] [Full Text: https://doi.org/10.3109/03630269308997491]

  1185. Yamashiro, Y., Hattori, Y., Matsuno, Y., Ohba, Y., Miyaji, T., Yamamoto, K., Yamamoto, K., Nakayama, Y., Abe, Y. Another example of Japanese beta-thalassemia [031 cap (A-to-G)]. Hemoglobin 13: 761-767, 1989. [PubMed: 2634674] [Full Text: https://doi.org/10.3109/03630268908998851]

  1186. Yanase, T., Hanada, M., Seita, M., Ohya, I., Ohta, Y., Imamura, T., Fujimura, T., Kawasaki, K., Yamaoka, K. Molecular basis of morbidity from a series of studies of hemoglobinopathies in western Japan. Jpn. J. Hum. Genet. 13: 40-53, 1968. [PubMed: 5750181]

  1187. Yang, K. G., Kutlar, F., George, E., Wilson, J. B., Kutlar, A., Stoming, T. A., Gonzalez-Redondo, J. M., Huisman, T. H. J. Molecular characterization of beta-globin gene mutations in Malay patients with Hb E-beta-thalassaemia and thalassaemia major. Brit. J. Haemat. 72: 73-80, 1989. [PubMed: 2736244] [Full Text: https://doi.org/10.1111/j.1365-2141.1989.tb07655.x]

  1188. Yapo, A. P., Prome, D., Claparols, C., Riou, J., Galacteros, F., Wajcman, H. Hb Yaounde (beta-134(H12)val-to-ala), a new neutral variant found in association with Hb Kenitra (beta-69(E13)gly-to-arg) in a patient from Cameroon. Hemoglobin 25: 97-101, 2001. [PubMed: 11300355] [Full Text: https://doi.org/10.1081/hem-100103074]

  1189. Yeager, A. M., Zinkham, W. H., Jue, D. L., Winslow, R. M., Johnson, M. H., McGuffey, J. E., Moo-Penn, W. F. Hemoglobin Cheverly: an unstable hemoglobin associated with chronic mild anemia. Pediat. Res. 17: 503-507, 1983. [PubMed: 6877904] [Full Text: https://doi.org/10.1203/00006450-198306000-00016]

  1190. Yoon, K., Cole-Strauss, A., Kmiec, E. B. Targeted gene correction of episomal DNA in mammalian cells mediated by a chimeric RNA-DNA oligonucleotide. Proc. Nat. Acad. Sci. 93: 2071-2076, 1996. [PubMed: 8700887] [Full Text: https://doi.org/10.1073/pnas.93.5.2071]

  1191. Zak, S. J., Brimhall, B., Jones, R. T., Kaplan, M. E. Hemoglobin Andrew-Minneapolis (beta 144 lys-to-asn): a new high-oxygen affinity mutant human hemoglobin. Blood 44: 543-549, 1974. [PubMed: 4413656]

  1192. Zeng, F., Rodgers, G. P., Huang, S., Schechter, A. N., Salamah, M., Perrine, S., Berg, P. E. Sequence of the -530 region of the beta-globin gene of sickle cell anemia patients with the Arabian haplotype. Hum. Mutat. 3: 163-165, 1994. [PubMed: 8199597] [Full Text: https://doi.org/10.1002/humu.1380030213]

  1193. Zeng, Y., Huang, S., Ren, Z., Li, H. Identification of Hb D-Punjab gene: application of DNA amplification in the study of abnormal hemoglobins. Am. J. Hum. Genet. 44: 886-889, 1989. [PubMed: 2729278]

  1194. Zeng, Y., Huang, S., Tao, Y., Wang, B., Gu, Y., Chen, R. Hemoglobin G-Taipei in three additional Chinese families. Hemoglobin 5: 731-735, 1981. [PubMed: 7338475] [Full Text: https://doi.org/10.3109/03630268108991841]

  1195. Zeng, Y., Huang, S. Hemoglobin New York (beta 113(G15) val-to-glu) in China. Hemoglobin 6: 61-67, 1982. [PubMed: 7068436]

  1196. Zeng, Y. T., Ren, Z. R., Chen, M. J., Zhao, J. Q., Qiu, X. K., Huang, S. Z. A new unstable haemoglobin variant: Hb Shanghai (beta131(H9)gln-to-pro) found in China. Brit. J. Haemat. 67: 221-223, 1987. [PubMed: 3676109] [Full Text: https://doi.org/10.1111/j.1365-2141.1987.tb02330.x]

  1197. Zhao, W., Wilson, J. B., Huisman, T. H. J., Sciarratta, G. V., Ivaldi, G., Petrini, C., Ripamonti, M. Hb Camperdown or beta104(G6)arg-to-ser in two Italian males. Hemoglobin 14: 459-461, 1990. [PubMed: 2283301] [Full Text: https://doi.org/10.3109/03630269009032008]

  1198. Zhao, W., Wilson, J. B., Webber, B. B., Huisman, T. H. J., Sciarratta, G. V., Ivaldi, G., Ripamonti, M. A second observation of Hb Abruzzo [beta143(H21)his-to-arg] in an Italian family. Hemoglobin 14: 463-466, 1990. [PubMed: 2283302] [Full Text: https://doi.org/10.3109/03630269009032009]

  1199. Zhu, L. H., Li, M., Wang, S. J. Hemoglobin J-Guantanamo (beta128 (H6) ala-to-asp) found in a Chinese family. Hemoglobin 12: 189-192, 1988. [PubMed: 3384711] [Full Text: https://doi.org/10.3109/03630268808998025]

  1200. Zimmerman, S. A., O'Branski, E. E., Rosse, W. F., Ware, R. E. Hemoglobin S/O(Arab): thirteen new cases and review of the literature. Am. J. Hemat. 60: 279-284, 1999. [PubMed: 10203101] [Full Text: https://doi.org/10.1002/(sici)1096-8652(199904)60:4<279::aid-ajh5>3.0.co;2-2]

  1201. Zinkham, W. H., Houtchens, R. A., Caughey, W. S. Carboxyhemoglobin levels in an unstable hemoglobin disorder (Hb Zurich): effect on phenotypic expression. Science 209: 406-408, 1980. [PubMed: 7384813] [Full Text: https://doi.org/10.1126/science.7384813]

  1202. Zinkham, W. H., Houtchens, R. A., Caughey, W. S. Relation between variations in the phenotypic expression of an unstable hemoglobin disorder (hemoglobin Zurich) and carboxyhemoglobin levels. Am. J. Med. 74: 23-29, 1983. [PubMed: 6849326] [Full Text: https://doi.org/10.1016/0002-9343(83)91113-0]

  1203. Zinkham, W. H., Liljestrand, J. D., Dixon, S. M., Hutchison, J. L. Observations on the rate and mechanism of hemolysis in individuals with Hb Zurich (His E7 (63) beta-to-arg): II. Thermal denaturation of hemoglobin as a cause of anemia during fever. Johns Hopkins Med. J. 144: 109-116, 1979. [PubMed: 439565]

  1204. Zinkham, W. H., Vangrov, J. S., Dixon, S. M., Hutchison, J. L. Observations on the rate and mechanism of hemolysis in individuals with Hb Zurich (His E7 (63) beta-to-arg): I. Concentrations of haptoglobin and hemopexin in the serum. Johns Hopkins Med. J. 144: 37-40, 1979. [PubMed: 762915]


Contributors:
Carol A. Bocchini - updated : 08/23/2023
Kelly A. Przylepa - updated : 08/03/2021
Carol A. Bocchini - updated : 11/14/2019
Cassandra L. Kniffin - updated : 2/14/2013
Cassandra L. Kniffin - updated : 1/22/2013
Ada Hamosh - updated : 11/1/2012
Paul J. Converse - updated : 2/13/2012
Ada Hamosh - updated : 1/4/2012
Paul J. Converse - updated : 11/17/2011
Carol A. Bocchini - updated : 5/20/2011
Ada Hamosh - updated : 9/29/2010
Paul J. Converse - updated : 5/14/2010
Patricia A. Hartz - updated : 1/28/2010
Paul J. Converse - updated : 11/11/2009
Carol A. Bocchini - updated : 5/22/2009
Paul J. Converse - updated : 3/13/2008
Cassandra L. Kniffin - updated : 2/20/2008
George E. Tiller - updated : 1/3/2008
Matthew B. Gross - updated : 7/5/2007
Victor A. McKusick - updated : 2/26/2007
Victor A. McKusick - updated : 11/21/2006
Victor A. McKusick - updated : 10/19/2006
Victor A. McKusick - updated : 9/19/2006
Victor A. McKusick - updated : 3/29/2006
George E. Tiller - updated : 2/17/2006
Victor A. McKusick - updated : 1/30/2006
George E. Tiller - updated : 1/23/2006
Victor A. McKusick - updated : 10/10/2005
Victor A. McKusick - updated : 10/3/2005
Victor A. McKusick - updated : 8/11/2005
Ada Hamosh - updated : 7/27/2005
Victor A. McKusick - updated : 6/20/2005
Victor A. McKusick - updated : 5/11/2005
Victor A. McKusick - updated : 3/7/2005
Victor A. McKusick - updated : 3/3/2005
Ada Hamosh - updated : 2/1/2005
Victor A. McKusick - updated : 12/9/2004
Victor A. McKusick - updated : 12/6/2004
Victor A. McKusick - updated : 10/26/2004
John A. Phillips, III - updated : 9/24/2004
Victor A. McKusick - updated : 9/21/2004
Victor A. McKusick - updated : 8/6/2004
Victor A. McKusick - updated : 6/2/2004
Victor A. McKusick - updated : 2/2/2004
Victor A. McKusick - updated : 1/20/2004
Victor A. McKusick - updated : 1/15/2004
Victor A. McKusick - updated : 4/17/2003
Victor A. McKusick - updated : 3/4/2003
Victor A. McKusick - updated : 3/3/2003
Victor A. McKusick - updated : 11/19/2002
Victor A. McKusick - updated : 10/2/2002
Victor A. McKusick - updated : 9/27/2002
Victor A. McKusick - updated : 9/16/2002
Victor A. McKusick - updated : 8/15/2002
Victor A. McKusick - updated : 6/3/2002
Victor A. McKusick - updated : 5/31/2002
Victor A. McKusick - updated : 5/23/2002
Victor A. McKusick - updated : 4/18/2002
Victor A. McKusick - updated : 4/16/2002
Victor A. McKusick - updated : 4/4/2002
Victor A. McKusick - updated : 2/27/2002
Victor A. McKusick - updated : 1/22/2002
Ada Hamosh - updated : 11/15/2001
Victor A. McKusick - updated : 11/2/2001
Victor A. McKusick - updated : 11/1/2001
Victor A. McKusick - updated : 10/10/2001
Victor A. McKusick - updated : 2/28/2001
Victor A. McKusick - updated : 2/14/2001
Victor A. McKusick - updated : 11/3/2000
Ada Hamosh - updated : 10/19/2000
Victor A. McKusick - updated : 8/31/2000
Victor A. McKusick - updated : 8/16/2000
Victor A. McKusick - updated : 7/21/2000
George E. Tiller - updated : 5/2/2000
Victor A. McKusick - updated : 4/26/2000
Victor A. McKusick - updated : 4/26/2000
Victor A. McKusick - updated : 4/11/2000
Victor A. McKusick - updated : 1/21/2000
Victor A. McKusick - updated : 1/18/2000
Carol A. Bocchini - updated : 12/14/1999
Victor A. McKusick - updated : 12/8/1999
Victor A. McKusick - updated : 9/15/1999
Matthew B. Gross - updated : 8/26/1999
Victor A. McKusick - updated : 8/25/1999
Victor A. McKusick - updated : 8/13/1999
Wilson H. Y. Lo - updated : 8/12/1999
Victor A. McKusick - updated : 7/20/1999
Ada Hamosh - updated : 6/27/1999
Victor A. McKusick - updated : 5/24/1999
Victor A. McKusick - updated : 12/21/1998
Stylianos E. Antonarakis - updated : 12/13/1998
Victor A. McKusick - updated : 11/19/1998
Victor A. McKusick - updated : 8/26/1998
Victor A. McKusick - edited : 8/19/1998
Victor A. McKusick - updated : 4/30/1998
Victor A. McKusick - updated : 3/31/1998
Victor A. McKusick - updated : 2/17/1998
Victor A. McKusick - updated : 11/5/1997
Victor A. McKusick - updated : 9/29/1997
Victor A. McKusick - updated : 9/11/1997
Victor A. McKusick - updated : 8/13/1997
Victor A. McKusick - updated : 5/28/1997
Victor A. McKusick - updated : 2/28/1997
Victor A. McKusick - edited : 2/21/1997
Iosif W. Lurie - updated : 1/17/1997
Moyra Smith - updated : 9/5/1996
Moyra Smith - updated : 8/15/1996
Orest Hurko - updated : 6/13/1995

Creation Date:
Victor A. McKusick : 6/24/1986

Edit History:
alopez : 09/15/2023
carol : 09/15/2023
carol : 08/23/2023
alopez : 07/19/2023
carol : 02/13/2023
carol : 02/10/2023
alopez : 07/07/2022
carol : 03/11/2022
carol : 02/22/2022
carol : 02/21/2022
carol : 12/13/2021
alopez : 08/03/2021
carol : 11/14/2019
alopez : 07/16/2019
alopez : 11/07/2018
carol : 09/24/2018
carol : 07/25/2018
carol : 05/21/2018
carol : 05/10/2018
alopez : 12/12/2017
alopez : 12/11/2017
carol : 04/26/2017
mgross : 03/10/2017
carol : 02/27/2017
joanna : 07/20/2016
carol : 07/19/2016
carol : 07/14/2016
carol : 7/14/2016
carol : 7/12/2016
carol : 7/9/2016
carol : 7/7/2016
carol : 6/23/2016
carol : 6/13/2016
alopez : 4/10/2015
carol : 2/17/2015
carol : 11/10/2014
carol : 11/10/2014
carol : 9/12/2014
joanna : 9/12/2014
terry : 3/14/2013
alopez : 2/20/2013
ckniffin : 2/14/2013
carol : 2/6/2013
ckniffin : 1/22/2013
carol : 12/12/2012
alopez : 11/2/2012
terry : 11/1/2012
alopez : 9/21/2012
terry : 7/6/2012
carol : 2/27/2012
mgross : 2/16/2012
terry : 2/13/2012
alopez : 1/12/2012
terry : 1/4/2012
joanna : 12/20/2011
mgross : 11/17/2011
carol : 6/13/2011
carol : 5/23/2011
carol : 5/20/2011
terry : 5/20/2011
terry : 5/20/2011
terry : 5/20/2011
carol : 5/20/2011
carol : 5/18/2011
terry : 11/3/2010
terry : 10/12/2010
terry : 10/12/2010
alopez : 10/5/2010
terry : 9/29/2010
carol : 8/5/2010
mgross : 5/17/2010
mgross : 5/17/2010
terry : 5/14/2010
wwang : 3/26/2010
alopez : 1/28/2010
carol : 1/8/2010
terry : 12/16/2009
mgross : 12/1/2009
mgross : 12/1/2009
terry : 11/11/2009
wwang : 7/29/2009
carol : 6/3/2009
carol : 5/22/2009
carol : 5/22/2009
terry : 2/4/2009
terry : 1/14/2009
mgross : 3/19/2008
mgross : 3/19/2008
terry : 3/13/2008
wwang : 3/6/2008
ckniffin : 2/20/2008
wwang : 1/11/2008
terry : 1/3/2008
terry : 8/9/2007
mgross : 7/5/2007
alopez : 3/21/2007
terry : 2/26/2007
alopez : 11/27/2006
terry : 11/21/2006
alopez : 10/23/2006
terry : 10/19/2006
wwang : 10/3/2006
terry : 9/19/2006
terry : 6/23/2006
alopez : 5/5/2006
terry : 3/29/2006
wwang : 3/2/2006
terry : 2/17/2006
alopez : 2/7/2006
terry : 1/30/2006
carol : 1/24/2006
wwang : 1/23/2006
carol : 1/19/2006
alopez : 10/10/2005
alopez : 10/7/2005
terry : 10/3/2005
carol : 10/3/2005
carol : 10/3/2005
terry : 9/27/2005
wwang : 8/18/2005
terry : 8/11/2005
terry : 8/3/2005
alopez : 7/28/2005
terry : 7/27/2005
carol : 7/19/2005
alopez : 6/22/2005
terry : 6/20/2005
wwang : 6/7/2005
wwang : 5/12/2005
terry : 5/11/2005
tkritzer : 3/11/2005
terry : 3/7/2005
terry : 3/4/2005
terry : 3/3/2005
tkritzer : 2/1/2005
tkritzer : 1/25/2005
terry : 12/9/2004
terry : 12/6/2004
terry : 11/3/2004
tkritzer : 10/28/2004
terry : 10/26/2004
terry : 10/26/2004
alopez : 9/24/2004
tkritzer : 9/23/2004
terry : 9/21/2004
tkritzer : 8/10/2004
terry : 8/6/2004
tkritzer : 6/8/2004
terry : 6/2/2004
alopez : 5/27/2004
terry : 5/20/2004
tkritzer : 4/7/2004
terry : 4/2/2004
carol : 3/17/2004
tkritzer : 2/2/2004
terry : 2/2/2004
tkritzer : 1/22/2004
terry : 1/20/2004
terry : 1/15/2004
carol : 11/24/2003
alopez : 11/14/2003
alopez : 11/14/2003
alopez : 11/10/2003
cwells : 11/7/2003
carol : 8/25/2003
terry : 7/30/2003
carol : 5/13/2003
carol : 5/13/2003
tkritzer : 4/30/2003
terry : 4/17/2003
carol : 3/11/2003
tkritzer : 3/7/2003
tkritzer : 3/7/2003
terry : 3/4/2003
terry : 3/3/2003
tkritzer : 12/31/2002
tkritzer : 11/27/2002
tkritzer : 11/20/2002
terry : 11/19/2002
tkritzer : 10/7/2002
tkritzer : 10/3/2002
tkritzer : 10/3/2002
tkritzer : 10/3/2002
tkritzer : 10/2/2002
tkritzer : 10/2/2002
carol : 9/27/2002
carol : 9/16/2002
tkritzer : 8/20/2002
tkritzer : 8/16/2002
terry : 8/15/2002
carol : 7/29/2002
alopez : 6/18/2002
terry : 6/3/2002
terry : 5/31/2002
terry : 5/31/2002
alopez : 5/28/2002
terry : 5/23/2002
cwells : 5/1/2002
cwells : 4/24/2002
terry : 4/18/2002
terry : 4/16/2002
cwells : 4/15/2002
cwells : 4/10/2002
terry : 4/4/2002
cwells : 3/22/2002
cwells : 3/20/2002
terry : 2/27/2002
terry : 2/8/2002
carol : 2/5/2002
mcapotos : 1/31/2002
terry : 1/22/2002
alopez : 11/15/2001
terry : 11/15/2001
carol : 11/8/2001
carol : 11/8/2001
mcapotos : 11/2/2001
mcapotos : 11/2/2001
mcapotos : 11/1/2001
mcapotos : 11/1/2001
carol : 10/12/2001
carol : 10/12/2001
terry : 10/10/2001
terry : 2/28/2001
carol : 2/26/2001
terry : 2/26/2001
carol : 2/20/2001
mcapotos : 2/19/2001
mcapotos : 2/16/2001
terry : 2/14/2001
mcapotos : 2/12/2001
mcapotos : 2/12/2001
mcapotos : 1/12/2001
mcapotos : 11/9/2000
terry : 11/3/2000
alopez : 10/19/2000
terry : 9/15/2000
terry : 8/31/2000
carol : 8/29/2000
terry : 8/16/2000
alopez : 7/26/2000
terry : 7/21/2000
terry : 7/21/2000
carol : 6/22/2000
alopez : 5/2/2000
mcapotos : 5/2/2000
mcapotos : 4/28/2000
mcapotos : 4/27/2000
terry : 4/26/2000
terry : 4/26/2000
terry : 4/11/2000
terry : 1/21/2000
mcapotos : 1/20/2000
mgross : 1/19/2000
terry : 1/18/2000
mcapotos : 12/15/1999
carol : 12/14/1999
carol : 12/9/1999
terry : 12/8/1999
carol : 10/5/1999
mgross : 9/22/1999
mgross : 9/21/1999
terry : 9/15/1999
carol : 9/8/1999
carol : 8/26/1999
mgross : 8/26/1999
mgross : 8/25/1999
mgross : 8/13/1999
mgross : 8/12/1999
mgross : 8/12/1999
jlewis : 8/5/1999
terry : 7/20/1999
kayiaros : 7/13/1999
kayiaros : 7/13/1999
carol : 6/27/1999
carol : 5/24/1999
joanna : 5/20/1999
carol : 12/29/1998
terry : 12/21/1998
carol : 12/13/1998
carol : 11/25/1998
terry : 11/19/1998
joanna : 11/19/1998
carol : 8/27/1998
terry : 8/26/1998
terry : 8/19/1998
dkim : 7/24/1998
dkim : 7/21/1998
dkim : 7/21/1998
carol : 6/26/1998
terry : 6/18/1998
terry : 6/18/1998
terry : 6/18/1998
alopez : 6/9/1998
dholmes : 6/8/1998
alopez : 5/14/1998
carol : 5/12/1998
terry : 4/30/1998
alopez : 3/31/1998
terry : 3/24/1998
mark : 3/2/1998
terry : 2/17/1998
jenny : 11/7/1997
terry : 11/5/1997
mark : 10/28/1997
mark : 10/10/1997
jenny : 10/1/1997
terry : 9/29/1997
terry : 9/26/1997
dholmes : 9/26/1997
dholmes : 9/19/1997
jenny : 9/18/1997
terry : 9/11/1997
terry : 9/8/1997
terry : 8/13/1997
joanna : 8/12/1997
terry : 8/6/1997
terry : 8/6/1997
alopez : 7/31/1997
alopez : 7/28/1997
terry : 7/10/1997
alopez : 7/10/1997
mark : 7/10/1997
mark : 7/10/1997
alopez : 7/10/1997
mark : 7/8/1997
mark : 7/8/1997
mark : 7/8/1997
terry : 7/7/1997
jenny : 6/3/1997
terry : 5/28/1997
mark : 2/28/1997
terry : 2/26/1997
mark : 2/21/1997
jamie : 1/17/1997
jamie : 1/15/1997
terry : 1/7/1997
mark : 12/23/1996
terry : 12/18/1996
terry : 12/17/1996
terry : 12/5/1996
terry : 11/18/1996
terry : 11/15/1996
terry : 11/13/1996
terry : 11/5/1996
terry : 10/31/1996
jamie : 10/30/1996
mark : 9/11/1996
mark : 9/5/1996
terry : 9/5/1996
terry : 9/5/1996
marlene : 9/3/1996
mark : 8/15/1996
mark : 7/9/1996
mark : 7/2/1996
terry : 6/25/1996
mark : 6/19/1996
terry : 6/12/1996
terry : 6/5/1996
mark : 4/22/1996
terry : 4/15/1996
mark : 3/30/1996
mark : 3/21/1996
terry : 3/21/1996
mark : 3/11/1996
terry : 2/28/1996
mark : 2/13/1996
terry : 2/5/1996
mark : 1/28/1996
terry : 1/23/1996
mark : 1/10/1996
mark : 1/4/1996
mark : 1/4/1996
mark : 1/4/1996
mark : 11/13/1995
terry : 10/31/1995
davew : 8/25/1994
jason : 7/29/1994
pfoster : 4/5/1994