Association of a novel high oxygen affinity haemoglobin variant with delta beta thalassaemia.
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.
Rochette
J
J
MRC Molecular Haematology Unit, John Radcliffe Hospital, Oxford.
Barnetson
R
R
Kiger
L
L
Kister
J
J
Littlewood
T J
TJ
Webster
R
R
Poyart
C
C
Thein
S L
SL
D000328:Adult; D001483:Base Sequence; D015139:Blotting, Southern; D004247:DNA / Q000737:chemistry; D005260:Female; D005914:Globins / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010100:Oxygen / Q000097:blood*; D016133:Polymerase Chain Reaction; D017086:beta-Thalassemia / Q000097:blood / Q000235:genetics*
D006455:Hemoglobins, Abnormal; D005914:Globins; D004247:DNA; D010100:Oxygen