title: Black beta-thalassemia homozygotes with specific sequence variations in the 5' hypersensitive site-2 of the locus control region have high levels of fetal hemoglobin.
abstract: We have sequenced the 5' hypersensitive-2 (5'HS-2) site of the locus control region (LCR) and the promoters of the two gamma-globin genes located on chromosome 11 of a black patient with mild beta-thalassemia (beta-thal) major due to a homozygosity for the C----T mutation at position -88 of the beta promoter and with a high Hb F level. Sequence variations in the 5'HS-2 were the same as observed for the beta s chromosome with haplotype number 3, while most of the G gamma promoter and the A gamma promoter had sequences similar to that of the beta S chromosome with haplotype number 19. This atypical haplotype (number 19A) is apparently associated with an increased gamma chain production which is particularly evident during periods of severe hematopoietic stress. Additional studies on relatives of the proband and on 10 unrelated black beta-thal homozygotes with either the C----T mutation at -88 or the A----G mutation at -29, confirm the possible importance of the sequence differences in the 5'HS-2, and also suggest that at least two additional factors, namely a C----T mutation at position -158 of the G gamma promoter and a relative deficiency in alpha chain synthesis play a (perhaps less important) role in the increased Hb F synthesis in these patients.
authors.affiliation: Division d'Hematologie, Centre de Transfusion Sanguine, Hopital Cantonal Universitaire de Geneve, Suisse.
authors.forename: P
authors.initials: P
authors.lastname: Beris
authors.forename: M N
authors.initials: MN
authors.lastname: Kitundu
authors.forename: E
authors.initials: E
authors.lastname: Baysal
authors.forename: C
authors.initials: C
authors.lastname: Oner
authors.forename: K D
authors.initials: KD
authors.lastname: Lanclos
authors.forename: A J
authors.initials: AJ
authors.lastname: Dimovski
authors.forename: F
authors.initials: F
authors.lastname: Kutlar
authors.forename: T H
authors.initials: TH
authors.lastname: Huisman
mesh_terms: D000225:Adenine / Q000032:analysis; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D002648:Child; D002880:Chromosomes, Human, Pair 11; D003596:Cytosine / Q000032:analysis; D004247:DNA / Q000032:analysis / Q000235:genetics; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics* / Q000378:metabolism; D005796:Genes / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005914:Globins / Q000235:genetics / Q000378:metabolism; D006147:Guanine / Q000032:analysis; D006239:Haplotypes / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013941:Thymine / Q000032:analysis; D017086:beta-Thalassemia / Q000235:genetics* / Q000378:metabolism
chemical_list: D006147:Guanine; D003596:Cytosine; D005914:Globins; D004247:DNA; D005319:Fetal Hemoglobin; D000225:Adenine; D013941:Thymine