title: Levels of Hb A2 in heterozygotes and homozygotes for beta-thalassemia mutations: influence of mutations in the CACCC and ATAAA motifs of the beta-globin gene promoter.
abstract: The author summarizes the Hb A2 levels in over 600 beta-thalassemia heterozygotes with 32 different base changes or frameshifts and in 22 heterozygotes for 1 of 5 large deletions. Three major groups are recognized: persons with beta zero-thalassemia or beta (+)-thalassemia (severe) have Hb A2 levels between 4.5 and 5.5%, those with mild beta (+)-thalassemia alleles have levels between 3.6 and 4.2%, with still lower values for those with silent mutations. High values were observed in subjects with the 2 mild beta + alleles with mutations in the beta-globin gene promoter (-88, C-->T and -29, A-->G); unusually high Hb A2 values were also present in several -88 and -29 homozygotes. Data for several members of 8 families in which the -88 (C-->T) or the -29 (A-->G) mutation, or the -1,393-bp deletion, is present in cis or in trans to a delta-globin gene mutation support earlier observations that an increase in delta-chain synthesis occurs in cis to either one of these 3 alleles. A review of these data confirms the suggestion that the increase in Hb A2 levels results from at least two mechanisms: in a posttranslational system, the formation of alpha delta-dimers is promoted when excess alpha-chains are available, while certain promoter mutations increase the transcription of the delta-globin gene in cis because of a change in the binding of transcription factors.
authors.affiliation: Medical College of Georgia, Augusta 30912-2114, USA.
authors.forename: T H
authors.initials: TH
authors.lastname: Huisman
mesh_terms: D000328:Adult; D002648:Child; D005260:Female; D006580:Genetic Carrier Screening; D006443:Hemoglobin A2 / Q000032:analysis / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011401:Promoter Regions, Genetic / Q000235:genetics; D017086:beta-Thalassemia / Q000097:blood / Q000145:classification / Q000235:genetics*
chemical_list: D006443:Hemoglobin A2