Alternative titles; symbols
HGNC Approved Gene Symbol: KRT1
SNOMEDCT: 254170001;
Cytogenetic location: 12q13.13 Genomic coordinates (GRCh38): 12:52,674,736-52,680,407 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 12q13.13 | Epidermolytic hyperkeratosis 1 | 113800 | Autosomal dominant | 3 |
| Ichthyosis histrix, Curth-Macklin type | 146590 | Autosomal dominant | 3 | |
| Ichthyosis, annular epidermolytic 2 | 620148 | Autosomal dominant | 3 | |
| Keratosis palmoplantaris striata III | 607654 | 3 | ||
| Palmoplantar keratoderma, epidermolytic, 2 | 620411 | Autosomal dominant | 3 | |
| Palmoplantar keratoderma, nonepidermolytic | 600962 | Autosomal dominant | 3 |
Popescu et al. (1989) isolated 2 type II keratin genes, one coding for keratin-1, and another closely linked gene, 10 to 15 kb upstream, of unknown gene product.
Keratin-1 is a specific marker for terminal differentiation in mammalian epidermis. Data of Lessin et al. (1988) demonstrated that although genes K1 and K10 (148080) are coexpressed in terminally differentiated epidermis, they are not linked in the genome, implying the existence of trans-acting factors involved in the regulation of their expression.
Schimkat et al. (1990) demonstrated 4 isokeratin patterns by means of one-dimensional SDS electrophoresis of low-sulfur proteins in human hair. The phenotypes had the following frequencies: K1 = 70%, K1m = 18%, K3 = 9%, and K3m = 3%. Pedigree analysis and evaluation of observed and expected frequencies of the phenotypes led Schimkat et al. (1990) to conclude that the phenotypes are controlled by genes at 2 independent autosomal loci designated K and m. They suggested that the K3 and m alleles are dominant, whereas the K1 and non-m alleles are recessive.
In the mouse, alpha-keratin is encoded by a gene on chromosome 15 in a segment closely linked to that encoding the Hox3 genes (Nadeau, 1987). Homology of synteny would indicate that alpha-keratin is coded by a gene on chromosome 12, specifically in the segment 12q11-q21, in man. Indeed, by use of specific cDNA clones in conjunction with somatic cell hybrid analysis and in situ hybridization, Lessin et al. (1988) showed that the gene they referred to as K1, a type II keratin of 67 kD, maps to 12q11-q13. In somatic cell hybrid analysis, the K1 gene segregated concordantly with the HOX3 gene cluster.
By in situ hybridization, Popescu et al. (1989) localized the KRT1 gene to 12q11-q13.
Yoon et al. (1994) demonstrated that 8 previously known type II keratin genes are located in a cluster at 12q13 as determined by the study of a YAC contig. The cytogenetic location of the type II keratin cluster was established by fluorescence in situ hybridization. The 8 type II keratin genes assigned to that region were KRT1, KRT2, KRT4, KRT5, KRT6A, KRT6B, KRT7, and KRT8. Yoon et al. (1994) suspected that other keratin genes were located in the cluster. They identified one type I keratin gene, KRT18, situated next to its type II partner, KRT8, in this cluster.
Epidermolytic Hyperkeratosis 1
In a mother and son with epidermolytic hyperkeratosis (EHK1; 113800), Rothnagel et al. (1992) identified heterozygosity for a missense mutation in the KRT1 gene (E310Q; 139350.0001). Mutations in the KRT10 gene (148080) also cause EHK, a finding consistent with the fact that this keratin pair forms heterodimers and comprises the keratin intermediate filaments in the suprabasal epidermal cells.
In a large family with EHK1, Chipev et al. (1992) identified a missense mutation in the KRT1 gene (L160P; 139350.0002).
In a patient with severe EHK, Syder et al. (1994) demonstrated a missense mutation in the KRT1 gene (Y481C; 139350.0003).
In a woman with EHK, Whittock et al. (2001) identified heterozygosity for a V155D substitution in the KRT1 gene (139350.0007).
In 2 unrelated patients with primarily palmoplantar EHK, Lee et al. (2002) reported heterozygous mutations in the KRT1 gene, N187K (139350.0008) and L475P (139350.0009), respectively. The N187K variant previously had been identified in a 19-year-old man with severe ichthyosiform erythroderma and prominent palmoplantar hyperkeratosis with digital contractures by Nomura et al. (2001). The latter proband's mother had a milder phenotype and the N187K substitution was detected only faintly in her leukocyte DNA, suggesting mosaicism.
In a 17-year-male of Chinese ancestry who had an unusual form of epidermolytic hyperkeratosis with late onset (see 113800), Sprecher et al. (2003) identified heterozygosity for a 1-bp insertion in the KRT1 gene (139350.0015).
In a 23-year-old man with EHK, Smith et al. (2019) detected a heterozygous missense mutation in the KRT1 gene (L187P; 139350.0020).
Nonepidermolytic Palmoplantar Keratoderma
In a 4-generation family segregating autosomal dominant nonepidermolytic palmoplantar keratoderma (NEPPK; 600962) that mapped to chromosome 12q11-q13, Kimonis et al. (1994) identified a missense mutation in the V1 end domain of keratin-1 (K73I; 139350.0004).
In a father and daughter with mild NEPPK, Terron-Kwiatkowski et al. (2002) identified heterozygosity for a splice site mutation in the KRT1 gene (139350.0010). In an unrelated 8-year-old girl with NEPPK, they identified heterozygosity for a 24-bp deletion in KRT1 (139350.0011).
Annular Epidermolytic Ichthyosis 2
In affected individuals from 2 unrelated families with cyclic ichthyosis with epidermolytic hyperkeratosis (AEI2; 607602), Sybert et al. (1999) identified heterozygosity for 2 different missense mutations at the same residue in the KRT1 gene, I479T (139350.0005) and I479F (139350.0006).
In a 5-year-old girl with AEI, Zaki et al. (2018) identified heterozygosity for the previously reported I479T mutation in the KRT1 gene. Familial segregation was not reported.
Epidermolytic Palmoplantar Keratoderma 2
In 3 Scottish families with a mild form of epidermolytic palmoplantar keratoderma (EPPK2; 144200), Hatsell et al. (2001) identified a splice site mutation in the KRT1 gene (139350.0014).
In a 51-year-old Japanese man with EPPK2, Nakamizo et al. (2023) identified heterozygosity for an ala436-to-asp (A436D; 139350.0019) mutation in KRT1.
In 2 unrelated families with EPPK2, Gach et al. (2005) detected heterozygosity for an asn188-to-ser (N188S; 139350.0021) substitution in KRT1.
Ichthyosis Hystrix, Curth-Macklin Type
In a 3-generation African American family with the Curth-Macklin type of ichthyosis hystrix (IHCM; 146590), Sprecher et al. (2001) identified heterozygosity for a frameshift mutation in the KRT1 gene (139350.0013) that segregated fully with disease and was not found in African American or Caucasian controls.
In the 44-year-old male proband from a 3-generation African American family with IHCM, Richardson et al. (2006) sequenced the KRT1 gene and identified heterozygosity for a 1-bp deletion (139350.0016) that was not found in 30 chromosomes of African American controls. Familial segregation was not reported.
In a 5-year-old Japanese boy with IHCM, Kubo et al. (2011) analyzed exon 9 of the KRT1 gene and identified heterozygosity for a 1-bp insertion (139350.0017). The authors noted that similar to this case, the 2 mutations previously reported in patients with IHCM involved deletions and/or insertions with a frameshift located in the V2 tail domain of K1.
In a Colombian mother and daughter with IHCM, Fonseca et al. (2013) directly sequenced the KRT1 gene and identified heterozygosity for a 1-bp deletion (139350.0018) in the V2 domain. The authors noted that most patients with IHCM had mutations that truncated the first, second, or third glycine loops (GLs) in the V2 domain, whereas mutations that preserved GL1-GL3 but eliminated other GLs were associated with less severe phenotypes such as striate PPK or EHK, suggesting a potential genotype-phenotype correlation.
Keratosis Palmoplantaris Striata III
In a 4-generation family of British descent with keratosis palmoplantaris striata III (PPKS3; 607654) Whittock et al. (2002) identified a 1-bp deletion in the KRT1 gene (139350.0012). The authors noted that although the molecular defect was similar to a KRT1 mutation associated with ichthyosis hystrix (139350.0013), the changes in the keratin intermediate filaments were very different.
Reviews
Compton (1994) reviewed 31 known keratin mutations associated with EHK, EPPK, and epidermolysis bullosa simplex (see EBS1A; 131760) identified to that date: 7 in keratin-1, 5 in keratin-5 (148040), 8 in keratin-10 (148080), 4 in keratin-9 (607606), and 7 in keratin-14 (148066).
In a family (EHK-P) in which mother and son had epidermolytic hyperkeratosis (EHK1; 113800), Rothnagel et al. (1992) demonstrated heterozygosity for a G-to-C transversion predicted to result in substitution of glutamine for glutamic acid at position 310 of the keratin-1 protein (E310Q). The mutation was in the highly conserved carboxyl terminal of the rod domain of the protein. Structural analysis of the mutation predicted that heterodimer formation would be unaffected, although filament assembly and elongation would be severely compromised. The data implied that an intact keratin intermediate filament network is required for the maintenance of both cellular and tissue integrity. The affected persons in this family exhibited rare blistering neonatally and during treatment with retinoids. Otherwise, they suffered primarily from disseminated hyperkeratotic lesions over joints, hands, and feet.
In a large family with epidermolytic hyperkeratosis (EHK1; 113800) in which Compton et al. (1992) demonstrated linkage to the type II keratin gene cluster on 12q, Chipev et al. (1992) demonstrated a heterozygous CTT-to-CCT transition in codon 160 resulting in the substitution of proline for leucine (L160P). This nonconservative substitution in the H1 subdomain was predicted to introduce a significant change in protein structure.
In a patient (EH1) with severe epidermolytic hyperkeratosis (EHK1; 113800), Syder et al. (1994) demonstrated a heterozygous tyr481-to-cys (Y481) mutation in the KRT1 gene.
In a large family in which multiple members suffered from nonepidermolytic palmoplantar keratoderma (NEPPK; 600962), Kimonis et al. (1994) demonstrated linkage of the disorder with the type II keratin cluster on chromosome 12. The heterozygous mutation was a change of codon 73 from AAA to ATA. Sequence analysis identified a single base change in the amino-terminal V1 variable subdomain of keratin-1, resulting in a lys-to-ile substitution. This nonconservative mutation completely cosegregated with the disease and was not observed in 50 unrelated unaffected persons. They found that the V1 subdomain contains a 22-residue window that is conserved among most type II keratins. The altered lysine is an invariant residue in this conserved sequence. Previously described keratin mutations affect the central regions of the protein important for filament assembly and stability, and cause diseases characterized by cellular degeneration or disruption, e.g., epidermolytic palmoplantar keratoderma. The disease mutation described by Kimonis et al. (1994) was the first found in a keratin chain variable end region. The fact that epidermolysis was not associated supports the concept that the amino-terminal domain of keratins is involved in supramolecular interactions of keratin filaments rather than stability.
In a 5-year-old boy (TH) with cyclic ichthyosis with epidermolytic hyperkeratosis (AEI2; 607602), Sybert et al. (1999) demonstrated heterozygosity for a de novo c.1436T-C mutation in the KRT1 gene, predicting a change of isoleucine to threonine (I479T) in the highly conserved helix-termination motif. The mutation was not found in the proband's unaffected parents or sib, or in 50 healthy unrelated controls.
In an 18-year-old man (BM) with cyclic ichthyosis with epidermolytic hyperkeratosis (AEI2; 607620), Sybert et al. (1999) found a c.1435A-T mutation, predicting an isoleucine-to-phenylalanine substitution in codon 479 (I479F). His affected mother and maternal aunt were also heterozygous for the mutation, which was not found in 96 alleles from unaffected unrelated controls.
In a 39-year-old woman with epidermolytic hyperkeratosis (EHK1; 113800), Whittock et al. (2001) identified a heterozygous c.464T-A transversion (c.464T-A, NM_006121) in the KRT1 gene that resulted in a val155-to-asp (V155D) substitution within the H1 region of the keratin-1 rod domain. This valine residue is highly conserved among all type II keratins, suggesting that minor changes at this residue may affect keratin conformation.
In a patient (EHK-SJ) with primarily palmoplantar epidermolytic hyperkeratosis (EHK1; 113800) grade 2, Lee et al. (2002) reported a de novo heterozygous c.564C-A transversion (c.564C-A, NM_006121) in exon 1 of the KRT1 gene that resulted in an asn187-to-lys (N187K) mutation, at the eighth residue of the 1A rod domain segment. The mutation was not found among 50 unaffected control individuals.
In a 19-year-old male with severe ichthyosiform erythroderma and prominent palmoplantar hyperkeratosis with digital contractures, Nomura et al. (2001) identified the N187K mutation in the KRT1 gene. The mutation was recognized only faintly in the leukocyte DNA of his mother, who had a milder phenotype, suggesting that she was mosaic for the mutation.
Smith et al. (2019) referred to this mutation as ASN188LYS.
In a patient (EHK-AS) with primarily palmoplantar epidermolytic hyperkeratosis (EHK1; 113800) grade 2, Lee et al. (2002) reported a de novo heterozygous c.1457T-C transition (c.1457T-C, NM_006121) in exon 7 of the KRT1 gene that caused a leu475-to-pro (L475P) amino acid change, at the tenth residue from the end of 2B rod domain segment. The mutation was not found among 50 unaffected control individuals.
Smith et al. (2019) referred to this mutation as LEU486PRO.
In a 34-year-old man and his daughter, who both had mild diffuse PPK at birth (NEPPK; 600962) and developed mild flexural-limited scaling, Terron-Kwiatkowski et al. (2002) identified a heterozygous 5-prime donor splice site mutation in exon 1 (c.591+2T-A) of the KRT1 gene that predicted a 22-amino acid in-frame deletion in the keratin-1 1A domain. The mutation was not found in 50 controls from the local population.
In an 8-year-old girl with diffuse palmoplantar keratoderma at birth (NEPPK; 600962) who developed fine scaling over the lateral and anterior neck, lower back, external ears, and axillae, Terron-Kwiatkowski et al. (2002) identified a heterozygous in-frame deletion in exon 7 of the KRT1 gene (c.1376del24) that predicted a foreshortened 2B coiled-coil domain of keratin-1. The mutation was not found in 50 controls from the local population.
Whittock et al. (2002) reported a kindred affected with SPPK (607654) that was caused by a frameshift mutation, c.1628delG, within the V2 domain of keratin-1, which led to the partial loss of the glycine loop motif in the V2 domain and the gain of a novel 70-amino acid peptide. The authors noted that this mutation is very similar to one described by Sprecher et al. (2001) in a family with ichthyosis hystrix, a frameshift mutation within the third glycine loop (139350.0013), the only significant difference in molecular terms between the severe mutilating form of ichthyosis hystrix and milder SPPK being the number of glycine loops present. Whittock et al. (2002) stated that the changes in the keratin intermediate filaments produced by the 2 mutations were very different.
In a family with ichthyosis hystrix, Curth-Macklin type (IHCM; 146590), Sprecher et al. (2001) reported a c.5191GG-A mutation in exon 9 of the KRT1 gene leading to a frameshift and premature termination codon 229 bp downstream. The mutation occurred in a sequence encoding the V2 domain of K1 and was predicted to result in frameshift and translation of an aberrant and truncated protein tail of 77 residues, 32 residues shorter than the wildtype protein. Structural analyses disclosed a failure in keratin intermediate filament bundling, retraction of the cytoskeleton from the nucleus, and failed translocation of loricrin (152445) to the desmosomal plaques.
Variant Function
Ishida-Yamamoto et al. (2003) studied the distribution pattern of mutant K1 protein as well as the desmosomal ultrastructure in skin samples of a patient with IHCM by immunohistochemistry and immunoelectron microscopy. They referred to this mutation as c.1609-1610delGGinsA. Ishida-Yamamoto et al. (2003) showed that the predicted mutant K1 allele leading to IHCM is indeed expressed in vivo and not subjected to nonsense-mediated mRNA decay. Ishida-Yamamoto et al. (2003) suggested that this K1 mutant interferes with bundling of keratin intermediate filaments, possibly in a dominant-negative fashion, thus perturbing the keratin intermediate filament cytoskeleton. They found normal desmosome formation in IHCM, suggesting that the cytopathologic effects leading to hyperkeratosis and PPK in this disorder differ from those in SPPK, and may be related to abnormalities in supramolecular keratin intermediate filament organization and cytoplasmic trafficking of insoluble proteins, such as loricrin, as suggested by Sprecher et al. (2001). Ishida-Yamamoto et al. (2003) suggested that is also possible that mutant K1 affects shapes of the cells and integrity of other cellular structures, such as organelles and the nucleus, leading to gross alteration in the overall structures of the epidermis.
In 3 Scottish kindreds with a mild form of epidermolytic palmoplantar keratoderma (EPPK2; 620411), Hatsell et al. (2001) identified a c.4134G-A transition in the splice donor site of exon 6 of the KRT1 gene. The nucleotide substitution led to the utilization of a novel in-frame splice site 54 bases downstream of the mutation with the subsequent insertion of 18 amino acids into the 2B rod domain. This mutation appears to have had a milder effect than previously described mutations in the helix initiation and termination sequence on the function of the rod domain, with regard to filament assembly and stability. Affected individuals displayed only mild focal epidermolysis in the spinous layer of palmoplantar epidermis. The mutation was not found in 50 unrelated controls.
Sprecher et al. (2003) reported a 17-year-old male of Chinese ancestry who had an unusual variant epidermolytic hyperkeratosis (EHK1; 113800) phenotype with late onset. They determined that this individual was heterozygous for a de novo heterozygous single-nucleotide insertion (c.1752insG) in KRT1. As a result of the 1752insG mutation, the variable K1 end domain was predicted to be replaced by an aberrant sequence of 69 amino acids very rich in arginine and tryptophan residues that is 8 amino acids longer than the wildtype protein. The mutation eliminated 2 of the 10 glycine loops that are thought to be crucial for interactions of the K1 tail with proteins of the cornified cell envelope. The mutation was not found in the patient's parents, unaffected sister, or 200 unaffected control alleles. Sprecher et al. (2003) concluded that these changes are likely to alter significantly the structural and chemical characteristics of the K1 tail.
In the proband of a 3-generation African American family with the Curth-Macklin type of ichthyosis hystrix (IHCM; 146590), Richardson et al. (2006) identified heterozygosity for a 1-bp deletion (c.1556delG) in exon 9 of the KRT1 gene, causing a frameshift predicted to result in a K1 tail shortened by 48 residues, with replacement of glycine residues by alanine residues, thus altering the biochemical properties of the V2 domain and eliminating the E2 domain. The deletion was not found in 30 African American control chromosomes; familial segregation was not reported.
In a 5-year-old Japanese boy with the Curth-Macklin type of ichthyosis hystrix (IHCM; 146590), Kubo et al. (2011) identified heterozygosity for a 1-bp insertion (c.1861insT) in the KRT1 gene, predicted to disrupt the most C-terminal of 10 glycine loops and produce 32 aberrant amino acids in the tail domain of K1. There was no family history of a similar skin disorder; familial segregation of the insertion was not reported.
In a Colombian mother and daughter with the Curth-Macklin type of ichthyosis hystrix (IHCM; 146590), Fonseca et al. (2013) identified heterozygosity for a 1-bp deletion (c.1577delG) in the KRT1 gene, predicted to eliminate 9 of the 10 glycine loops in the V2 domain that are required for KRT1 dimerization with other proteins.
In a 51-year-old Japanese man with epidermolytic palmoplantar keratoderma (EPPK2; 620411), Nakamizo et al. (2023) identified heterozygosity for a c.1307C-A transversion in the KRT1 gene that resulted in an ala436-to-asp (A436D; 139350.0019) amino acid substitution. The mutation was identified by screening genes implicated in congenital skin disease. Functional studies were not performed.
In a 23-year-old man with epidermolytic hyperkeratosis (EHK1; 113800) , Smith et al. (2019) detected a novel heterozygous c.560T-C transition in exon 1 of the KRT1 gene, resulting in a leucine-to-proline substitution at codon 187 (L187P). The mutation occurred within the 1A domain of keratin 1. The patient presented as an adult with diffuse hyperkeratosis on his trunk, limbs, and acral sites, and severe flexion contractures of his fingers and toes; he was wheelchair-bound. He had a history of blistering, scaling, and erythroderma present at birth. Skin fragility and blistering occurred at sites of trauma.
In affected members of 2 unrelated families with epidermolytic palmoplantar keratoderma (EPPK2; 620411), Gach et al. (2005) identified heterozygosity for an asn188-to-ser (N188S) substitution in keratin-1. The authors noted that the numbering reflected counting the initiating methionine as position 1. The mutation occurred within the helix initiation motif at the N-terminal end of the central rod domain of keratin-1. The phenotype was described as Greither syndrome (transgrediens et progrediens palmoplantar keratoderma), indicating diffuse keratoderma of palms and soles extending to the back aspects (transgrediens) and involving the Achilles tendon. Gach et al. (2005) noted that the mutations N188S, N187S, and N188T had been described in 4 families with bullous congenital ichthyosiform erythroderma (BCIE; see 113800) with severe neonatal blistering followed by diffuse PPK with extensive epidermolytic hyperkeratosis. Similarly, in their family 2, a 13-year-old with PPK and transgrediens had a history of generalized blistering and erythroderma at birth that was initially described as BCIE.
Chipev, C. C., Korge, B. P., Markova, N., Bale, S. J., DiGiovanna, J. J., Compton, J. G., Steinert, P. M. A leucine-to-proline mutation in the H1 subdomain of keratin 1 causes epidermolytic hyperkeratosis. Cell 70: 821-828, 1992. [PubMed: 1381288] [Full Text: https://doi.org/10.1016/0092-8674(92)90315-4]
Compton, J. G., DiGiovanna, J. J., Santucci, S. K., Kearns, K. S., Amos, C. I., Abangan, D. L., Korge, B. P., McBride, O. W., Steinert, P. M., Bale, S. J. Linkage of epidermolytic hyperkeratosis to the type II keratin gene cluster on chromosome 12q. Nature Genet. 1: 301-305, 1992. [PubMed: 1284546] [Full Text: https://doi.org/10.1038/ng0792-301]
Compton, J. G. Epidermal disease: faulty keratin filaments take their toll. Nature Genet. 6: 6-7, 1994. [PubMed: 7511022] [Full Text: https://doi.org/10.1038/ng0194-6]
Fonseca, D. J., Rojas, R. F., Vergara, J. I., Rios, X., Uribe, C., Chavez, L., Velandia, F., Vargas, C. I., Restrepo, C. M., Laissue, P. A severe familial phenotype of Ichthyosis Curth-Macklin caused by a novel mutation in the KRT1 gene. Brit. J. Derm. 168: 456-458, 2013. [PubMed: 22834809] [Full Text: https://doi.org/10.1111/j.1365-2133.2012.11181.x]
Fraser, R. D. B., MacRae, T. P., Suzuki, E. Structure of the alpha-keratin microfibril. J. Molec. Biol. 108: 435-452, 1976. [PubMed: 1011259] [Full Text: https://doi.org/10.1016/s0022-2836(76)80129-5]
Gach, J. E., Munro, C. S., Lane, E. B., Wilson, N. J., Moss, C. Two families with Greither's syndrome caused by a keratin 1 mutation. J. Am. Acad. Derm. 53: S225-S230, 2005. [PubMed: 16227096] [Full Text: https://doi.org/10.1016/j.jaad.2005.01.139]
Hatsell, S. J., Eady, R. A., Wennerstrand, L., Dopping-Hepenstal, P., Leigh, I. M., Munro, C., Kelsell, D. P. Novel splice site mutation in keratin 1 underlies mild epidermolytic palmoplantar keratoderma in three kindreds. J. Invest. Derm. 116: 606-609, 2001. [PubMed: 11286630] [Full Text: https://doi.org/10.1046/j.1523-1747.2001.13041234.x]
Ishida-Yamamoto, A., Richard, G., Takahashi, H., Iizuka, H. In vivo studies of mutant keratin 1 in ichthyosis hystrix Curth-Macklin. J. Invest. Derm. 120: 498-500, 2003. [PubMed: 12603866] [Full Text: https://doi.org/10.1046/j.1523-1747.2003.12064.x]
Kimonis, V., DiGiovanna, J. J., Yang, J.-M., Doyle, S. Z., Bale, S. J., Compton, J. G. A mutation in the V1 end domain of keratin 1 in non-epidermolytic palmar-plantar keratoderma. J. Invest. Derm. 103: 764-769, 1994. [PubMed: 7528239] [Full Text: https://doi.org/10.1111/1523-1747.ep12412771]
Kubo, Y., Urano, Y., Matsuda, R., Ishigami, T., Murao, K., Arase, S., Ishida-Yamamoto, A. Ichthyosis hystrix, Curth-Macklin type: a new sporadic case with a novel mutation of keratin 1. Arch. Derm. 147: 999-1001, 2011. [PubMed: 21844476] [Full Text: https://doi.org/10.1001/archdermatol.2011.217]
Lee, D.-Y., Ahn, K.-S., Lee, C.-H., Rho, N.-K., Lee, J.-H., Lee, E.-S., Steinert, P. M., Yang, J.-M. Two novel mutations in the keratin 1 gene in epidermolytic hyperkeratosis. J. Invest. Derm. 119: 976-977, 2002. [PubMed: 12406348] [Full Text: https://doi.org/10.1046/j.1523-1747.2002.00061.x]
Lee, L. D., Ludwig, K., Baden, H. P. Matrix proteins of human hair as a tool for identification of individuals. Forensic Sci. 11: 115-121, 1978. [PubMed: 658856] [Full Text: https://doi.org/10.1016/s0379-0738(78)80004-8]
Lessin, S. R., Huebner, K., Isobe, M., Croce, C. M., Steinert, P. M. Chromosomal mapping of human keratin genes: evidence of non-linkage. J. Invest. Derm. 91: 572-578, 1988. [PubMed: 2461420] [Full Text: https://doi.org/10.1111/1523-1747.ep12477087]
Nadeau, J. H. Personal Communication. Bar Harbor, Me. 7/29/1987.
Nakamizo, S., Murata, T., Ishida, Y., Aoki, S., Sasaki, T., Kubo, A., Kabashima, K. A Japanese case of Vorner-type palmoplantar keratoderma caused by a novel KRT1 variant. J. Derm. 50: e307-e308, 2023. [PubMed: 37122192] [Full Text: https://doi.org/10.1111/1346-8138.16815]
Nomura, K., Umeki, K., Hatayama, I., Kuronuma, T. Phenotypic heterogeneity in bullous congenital ichthyosiform erythroderma: possible somatic mosaicism for keratin gene mutation in the mildly affected mother of the proband. Arch. Derm. 137: 1192-1195, 2001. [PubMed: 11559215] [Full Text: https://doi.org/10.1001/archderm.137.9.1192]
Popescu, N. C., Bowden, P. E., DiPaolo, J. A. Two type II keratin genes are localized on human chromosome 12. Hum. Genet. 82: 109-112, 1989. [PubMed: 2470667] [Full Text: https://doi.org/10.1007/BF00284039]
Richardson, E. S., Lee, J. B., Hyde, P. H., Richard, G. A novel mutation and large size polymorphism affecting the V2 domain of keratin 1 in an African-American family with severe, diffuse palmoplantar keratoderma of the ichthyosis hystrix Curth-Macklin type. J. Invest. Derm. 126: 79-84, 2006. [PubMed: 16417221] [Full Text: https://doi.org/10.1038/sj.jid.5700025]
Rothnagel, J. A., Dominey, A. M., Dempsey, L. D., Longley, M. A., Greenhalgh, D. A., Gagne, T. A., Huber, M., Frenk, E., Hohl, D., Roop, D. R. Mutations in the rod domains of keratins 1 and 10 in epidermolytic hyperkeratosis. Science 257: 1128-1130, 1992. [PubMed: 1380725] [Full Text: https://doi.org/10.1126/science.257.5073.1128]
Schimkat, M., Baur, M. P., Henke, J. Inheritance of some electrophoretic phenotypes of human hair. Hum. Genet. 85: 311-314, 1990. [PubMed: 1697558] [Full Text: https://doi.org/10.1007/BF00206752]
Smith, F. J. D., Kreuser-Genis, I. M., Jury, C. S., Wilson, N. J., Terron-Kwiatowski, A., Zamiri, M. Novel and recurrent mutations in keratin 1 cause epidermolytic ichthyosis and palmoplantar keratoderma. Clin. Exp. Derm. 44: 528-534, 2019. [PubMed: 30288772] [Full Text: https://doi.org/10.1111/ced.13800]
Sprecher, E., Ishida-Yamamoto, A., Becker, O. M., Marekov, L., Miller, C. J., Steinert, P. M., Neldner, K., Richard, G. Evidence for novel functions of the keratin tail emerging from a mutation causing ichthyosis hystrix. J. Invest. Derm. 116: 511-519, 2001. [PubMed: 11286616] [Full Text: https://doi.org/10.1046/j.1523-1747.2001.01292.x]
Sprecher, E., Yosipovitch, G., Bergman, R., Ciubutaro, D., Indelman, M., Pfendner, E., Goh, L. C., Miller, C. J., Uitto, J., Richard, G. Epidermolytic hyperkeratosis and epidermolysis bullosa simplex caused by frameshift mutations altering the V2 tail domains of keratin 1 and keratin 5. J. Invest. Derm. 120: 623-626, 2003. [PubMed: 12648226] [Full Text: https://doi.org/10.1046/j.1523-1747.2003.12084.x]
Sybert, V. P., Francis, J. S., Corden, L. D., Smith, L. T., Weaver, M., Stephens, K., McLean, W. H. I. Cyclic ichthyosis with epidermolytic hyperkeratosis: a phenotype conferred by mutations in the 2B domain of keratin K1. Am. J. Hum. Genet. 64: 732-738, 1999. [PubMed: 10053007] [Full Text: https://doi.org/10.1086/302278]
Syder, A. J., Yu, Q.-C., Paller, A. S., Giudice, G., Pearson, R., Fuchs, E. Genetic mutations in the K1 and K10 genes of patients with epidermolytic hyperkeratosis: correlation between location and disease severity. J. Clin. Invest. 93: 1533-1542, 1994. [PubMed: 7512983] [Full Text: https://doi.org/10.1172/JCI117132]
Terron-Kwiatkowski, A., Paller, A. S., Compton, J., Atherton, D. J., McLean, W. H. I., Irvine, A. D. Two cases of primarily palmoplantar keratoderma associated with novel mutations in keratin 1. J. Invest. Derm. 119: 966-971, 2002. [PubMed: 12406346] [Full Text: https://doi.org/10.1046/j.1523-1747.2002.00186.x]
Whittock, N. V., Ashton, G. H. S., Griffiths, W. A. D., Eady, R. A. J., McGrath, J. A. New mutations in keratin 1 that cause bullous congenital ichthyosiform erythroderma and keratin 2e that cause ichthyosis bullosa of Siemens. Brit. J. Derm. 145: 330-335, 2001. [PubMed: 11531804] [Full Text: https://doi.org/10.1046/j.1365-2133.2001.04327.x]
Whittock, N. V., Smith, F. J., Wan, H., Mallipeddi, R., Griffiths, W. A., Dopping-Hepenstal, P., Ashton, G. H., Eady, R. A., McLean, W. H. I., McGrath, J. A. Frameshift mutation in the V2 domain of human keratin 1 results in striate palmoplantar keratoderma. J. Invest. Derm. 118: 838-844, 2002. [PubMed: 11982762] [Full Text: https://doi.org/10.1046/j.1523-1747.2002.01750.x]
Yoon, S.-J., LeBlanc-Straceski, J., Ward, D., Krauter, K., Kucherlapati, R. Organization of the human keratin type II gene cluster at 12q13. Genomics 24: 502-508, 1994. [PubMed: 7536183] [Full Text: https://doi.org/10.1006/geno.1994.1659]
Zaki, T. D., Yoo, K.-Y., Kassardjian, M., Choate, K. A. A p.478I>T KRT1 mutation in a case of annular epidermolytic ichthyosis. Pediat. Derm. 35: e414-e415, 2018. [PubMed: 30152556] [Full Text: https://doi.org/10.1111/pde.13643]