Association of a novel high oxygen affinity haemoglobin variant with delta beta thalassaemia

Br J Haematol. 1994 Jan;86(1):118-24. doi: 10.1111/j.1365-2141.1994.tb03261.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Blotting, Southern
  • DNA / chemistry
  • Female
  • Globins / genetics
  • Hemoglobins, Abnormal / genetics
  • Hemoglobins, Abnormal / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Oxygen / blood*
  • Polymerase Chain Reaction
  • beta-Thalassemia / blood
  • beta-Thalassemia / genetics*

Substances

  • Hemoglobins, Abnormal
  • Globins
  • DNA
  • Oxygen