Hb Kurdistan [α47(CE5)ASP→TYR], A New α Chain Variant in Combination with β®-Thalasseuia

Abstract

We have characterized the structural abnormality of a new a chain mutant found in a Kurdish family. The clinical and hemato-logical investigation of eight individuals have shown that the a variant is associated with a β°-thalassemia mutation (nonsense codon 39). The tryptic peptide map and sequencing of the abnormal peptide revealed the substitution of an aspartic acid by a tyro-sine residue at position 47 of the a chain; furthermore, selective amplification and molecular analysis of both α genes have assigned the new mutation to the α2 gene. The variant, named Hb Kurdistan, is clinically silent but the percentage of this hemoglobin found in the only double heterozygote for β°-thalassemia and a-Kurdistan, presumably indicates a lower affinity of the abnormal chain for the β polypeptides.