Hb adana or α259(E8)Gly→Aspβ2, A severely unstable α1-globin variant, observed in combination with the -(α)20.5 KB α-thal-1 deletion in two Turkish patients

We have identified a severely unstable hemoglobin variant through sequencing of amplified DNA involving the α1-globin gene; the mutation is located in codon 59 (CCG CAG) andresults in a Gly—Asp replacement. This amino acid substitution concerns a glycine residue at an internal position in the E helix, which is in close contact with a glycine residue of the B helix; introduction of the larger and charged aspartic acid residue greatly affects the stability of the molecule. This variant was present in association with a common α-thalassemia-1 deletion [-(α)20.5 kb] in two adults and caused a severe type of Hb H disease with anemia, low levels of Hb A2, increased → chain, and Hb Bart's. In vitro chain synthesis in reticulocytes showed a high specific activity of the variant α chain. Only a minute quantity of Hb H was present but instead about 10% of Hb Bart's was observed. The increased synthesis of γ chains was likely due to specific characteristics of a chromosome with haplotype #3, which was present in both patients. The same family was studied 18 years ago [1]; the improved methodology presently available has led to a corrected diagnosis for these patients. © 1993 Wiley-Liss, Inc.