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. 1996 Oct;53(2):59-65.
doi: 10.1002/(SICI)1096-8652(199610)53:2<59::AID-AJH1>3.0.CO;2-2.

Variability in the fetal hemoglobin level of the normal adult

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Free article

Variability in the fetal hemoglobin level of the normal adult

Leonova JYe et al. Am J Hematol. 1996 Oct.
Free article

Abstract

We analyzed blood samples from more than 200 normal adults, and quantified their Hb F by cation-exchange high-performance liquid chromatography. In several subjects with slightly elevated Hb F (0.4-4.3%), we determined the Ggamma levels in the Hb F and DNA sequence variations in the locus control region II and in the Ggamma and Agamma promoters. About 25% of the approximately 200 normal teenaged high school students had elevated Hb F; detailed analyses of some 20 students, selected at random, identified most as females with a homozygosity for the C-->T variation at position -158 (Ggamma). One 11-year-old boy was heterozygous for the A-->G change at position -161 (Ggamma); he and two of his relatives had approximately 4% Hb F, high Ggamma values, and a high level of (mainly) Ggamma-mRNA. Nearly 40 normal adults from Macedonia and from Georgia (mostly Caucasians) were tentatively identified as Swiss HPFH heterozygotes because slightly elevated Hb F levels were observed at least once. Many of these persons were heterozygous or homozygous for the C-->T mutation at -158 (Ggamma), and a few carried a gamma-globin gene triplication. The C-->T change appears to be an important factor predisposing the adult to increased Hb F production. Evidence suggests a gene dose effect in (mildly) anemic adults; however, other factors besides the C-->T change at -158 (Ggamma), including factors not linked to the beta-globin region, may cause an increase in gamma-chain synthesis.

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