HB Hradec Kralove (HB HK) or α₂ β₂ 115(617)ALA→ASP, A Severely Unstable Hewglobin Variant Resulting in a Dominant β-Thalassemia Trait in a Czech Family

Abstract

We have identified through sequencing of amplified DNA a GCC→GAC mutation in codon 115 of the β-globin gene in a mother and daughter of a small Czech family. This base change was confirmed by hybridization with a 32P-labeled specific oligonucleotide probe and by gene mapping because it creates a new Ava II site. The mutation results in an Ala→Asp replacement at β115(617); this β chain is severely unstable and could not be identified either as chain or as hemoglobin variant by isoelectrofocusing and various high performance liquid chromatography methods. Stability tests were mildly positive in freshly prepared lysates, but an unstable hemoglobin could not be detected in older lysates with these methods. Its presence results in a dominant type of β-thalassemia in the two heterozygotes, with moderate anemia, reticulocytosis, nucleated red cells, target cells, and other red cell changes, Heinz body formation, and splenomegaly; the oldest of the two patients was splenectomized. Both subjects had a marked increase in fetal hemoglobin synthesis.