HB KURDISTAN [ALPHA-47(CE5)ASP-]TYR], A NEW ALPHA-CHAIN VARIANT IN COMBINATION WITH BETA-THALASSEMIA

We have characterized the structural abnormality of a new alpha chain mutant found in a Kurdish; family. The clinical and hematological inve stigation of eight individuals have shown that the a variant is associ ated with a beta degrees-thalassemia mutation (nonsense codon 39). The tryptic peptide map and sequencing of the abnormal peptide revealed t he substitution of an aspartic acid by a tyrosine residue at position 47 of the alpha chain; furthermore, selective amplification and molecu lar analysis of both alpha genes have assigned the new mutation to the alpha 2 gene. The variant, named Hb Kurdistan, is clinically silent b ut the percentage of this hemoglobin found in the only double heterozy gote for beta degrees-thalassemia and alpha-Kurdistan, presumably indi cates a lower affinity of the abnormal chain for the beta polypeptides .