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.

No abstract

We have identified a valine-->methionine mutation at position 67 of the beta chain in the hemoglobin of a young Russian patient with severe hemolytic disease, anemia, splenomegaly, Heinz body formation, and continued requirement for blood transfusions despite an early splenectomy. Sequencing of amplified DNA readily identified a GTG-->ATG mutation at codon 67. The introduction of the larger methionine residue into the heme pocket, and the loss of the bonds between valine at beta 67 and the heme group, adequately account for the severe instability of Hb Alesha and the serious clinical condition of its carrier.

No abstract

This report confirms the benign nature of homozygosity for Hb D.