Association of a novel high oxygen affinity haemoglobin variant with δβ thalassaemia

Publisher Website
Google Scholar
Abstract
We report an uncommon association of delta beta thalassaemia and a haemoglobin (Hb) variant with high oxygen affinity in an Asian Indian family. Minimal polycythaemia was seen in a heterozygote for this novel Hb variant, Hb Headington (beta 72 (E16) Ser-->Arg), while compound heterozygosity for Hb Headington and the Indian G gamma (A gamma delta beta)(0) thalassaemia produces a marked increase in erythrocytosis with a concomitant increase in the level of the variant Hb. The HbF in such compound heterozygotes remains at a level consistent with that usually observed in individuals heterozygous for the G gamma (A gamma delta beta)(0) thalassaemia alone. The purified Hb variant showed an increased oxygen affinity, moderately decreased co-operativity and a normal Bohr effect. Results of functional studies suggest that the high oxygen affinity of Hb Headington is due to the Ser-->Arg substitution which disrupts the normal and tight interaction between A, B and E helices leading to a destabilization of the T deoxy-structure of the abnormal haemoglobin.