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Association of a novel high oxygen affinity haemoglobin variant with δβ thalassaemia
Author(s) -
Rochette J.,
Barnetson R.,
Kiger L.,
Kister J.,
Littlewood T. J.,
Webster R.,
Poyart C.,
Thein S. L.
Publication year - 1994
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1994.tb03261.x
Subject(s) - polycythaemia , compound heterozygosity , bohr effect , heterozygote advantage , hemoglobinopathy , beta (programming language) , fetal hemoglobin , hemoglobin , microbiology and biotechnology , chemistry , loss of heterozygosity , oxygen , biology , genetics , medicine , hemolytic anemia , allele , biochemistry , gene , immunology , fetus , oxygen–haemoglobin dissociation curve , organic chemistry , pregnancy , computer science , programming language
We report an uncommon association of δβ 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 (β72 (E16) Ser→Arg), while compound heterozygosity for Hb Headington and the Indian G γ ( A γδβ) 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 γ ( A γδβ)° 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.