Gene: [11p155/HPFH1] hereditary persistence of fetal hemoglobin, heterocellular 1; F-cell production, heterocellular 1; [FCP ]


HET

 [1] Persistence of fetal hemoglobin (Hb-F), i.e. the continuing expression of gamma hemoglobin genes in postnatal life, is a heterogeneous group of phenotypically similar pathologies. In clinical genetic terms, two principal types are differentiated: pancellular type (majority of red blood cells synthesize Hb-F) and heterocellular one (only a portion of cells synthesize Hb-F).
[2] In molecular genetic terms, two groups of mutations associated with the persistence of Hb-F are differentiated: deletion mutations (in beta/delta thalassemias), where the genes for beta- and delta-globin peptides are lost; and nondeletion ones, representing single base substitutions in regulatory sites of the promoter region of gamma-A gene (transitions A for G in position -117, T for C in position -196, C for T in position -198, T for C in position -202 with respect to caping site) and gamma-G gene (transitions T for C and C for T in positions -158 and -175, respectively, and transversion G for C in position -202). Each type of persistence of Hb-F is determined by an independent gene (as follows from the formal genetic data on the disease inheritance and linkage with other genes, including the beta-globin gene cluster in 11p155). However, the physical localization of the respective sequences remains unclear. At least for pancellular form, some regulatory regions in 5'- and/or 3'-vicinities (and in introns) of gamma-A and gamma-B globin genes are supposed to represent such sequences (see GEM:11p155/HBG1 and GEM:11p155/HBG2).
[3] Another autosomal type of persistence of Hb-F exists, which is linked with neither beta- nor alpha-globin genes in chr 11p and chr 16p, respectively (Martinez-1989; see GEM:07q36/HPFH2).
[4] In addition, two X-linked types of Hb-F persistence are likely to exist. They are presumably determined by genes in the short arm of Chr X (GEM:0Xp1123/GATA1 and GEM:0Xp222/HPFHX)."

REL

 FAM:HBB/11p155.

REF

 LIN,MAP "Balsley &: Blood, 59, N4, 828-831, 1982
CAG,MUT,MOL "Boyer &: Blood, 64, 1053-1058, 1984
HIS,FOG,PAT "Boyer &: AJHG, 29, 256-271, 1977
CAG,MUT,MOL "Camaschella &: Blood, 73, N7, 1999-2002, 1989
CAG,MUT,MOL "Collins FS &: Nature, 313, N6000, 325-326, 1985
CAG,MUT,MOL "Collins FS &: PNAS, 81, 4894-4898, 1984
HET "Craig JE &: Nature Genet, 12, 58-64, 1996
LOC,LIN,MOL,CYG "Donald JA &: Hum Genet, 80, N1, 69-74, 1988
LIN,MAP "Dover GJ &: Science, 211, 1441-1444, 1981
CAG,MUT,MOL "Efremov GD &: Hum Genet, 77, 132-136, 1987
CAG,MUT,MOL "Farquhar &: AJHG, 35, 611-620, 1983
CAG,MUT,MOL "Gelinas RE &: Blood, 71, 1108-1112, 1988
CAG,MUT,MOL "Gelinas RE &: Nature, 313, N6000, 323-324, 1985
LIN,MAP "Giampaolo A &: Hum Genet, 66, 151-156, 1984
LIN,MAP "Gianni AM &: EMBO J, 2, 921-925, 1983
CAG,MUT,MOL "Giglioni B &: EMBO J, 3, N11, 2641-2645, 1984
CAG,MUT,MOL "Gilman JG: Hemoglobin, 12, N5-6, 707-716, 1988
LIN,MAP "Gilman JG, Huisman: Blood, 64, N2, 452-457, 1984
LIN,MAP "Jagadeeswaran P &: Nature, 296, (1 Apr), 469-470, 1982
HIS,FOG,PAT "Kan &: Nature, 258, 162-163, 1975
CAG,MUT,MOL "Kutlar A &: Biochem Genet, 22, N1-2, 21-35, 1984
LIN,MAP "Marinucci &: Hemoglobin, 5, 1-17, 1981
COM "Martinez G &: Hum Genet, 82, 335-337, 1989
LOC,LIN,MOL,CYG "Melis M &: PNAS, 84, N22, 8105-8109, 1987
LIN,MAP "Milner &: Blood, 63, 64-72, 1984
LIN,MAP "Old JM &: Science, 215, (19 Feb), 981-982, 1982
LIN,MAP "Ottolenghi S &: PNAS, 79, (Apr), 2347-2351, 1982
CAG,MUT,MOL "Ragusa A &: AJHG, 45, 106-111, 1989
HIS,FOG,PAT "Soummer AM &: Hum Genet, 57, 371-375, 1981
CAG,MUT,MOL "Tate VE &: Blood, 68, N6, 1389-1393, 1986
FOG "Thein SL &: AJHG, 54, 214-228, 1994
CAG,MUT,MOL "Tuan D &: PNAS, 80, 6937-6941, 1983
HIS,FOG,PAT "Weatherall &: Brit J Haematol, 29, 205-220, 1975
HIS,FOG,PAT "Wood WG &: Brit J Haematol, 36, 461-473, 1977
HIS,FOG,PAT "Wood WG &: Nature, 264, 247-249, 1976
HIS,FOG,PAT "Zago &: Blood, 53, 977-986, 1979

KEY

 hem, trp

CLA

 unknown, basic

LOC

 11 p15.5

MIM

 MIM: 142470

SYN

 FCP