Association of a novel high oxygen affinity haemoglobin variant with δβ thalassaemia |
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Authors: | J Rochette R Barnetson L Kiger J Kister T J Littlewood R Webster C Poyart S L Thein |
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Institution: | MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford;Biochimie Génétique, Hôpital Cochin, Paris, France;Inserm U299, Hôpital de Bicêtre, le Kremlin Bicêtre, France;Department of Haematology, John Radcliffe Hospital, Oxford |
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Abstract: | 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 Gγ (Aγδβ) 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 Gγ (Aγδβ)° 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. |
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Keywords: | thalassaemia haemoglobin high oxygen affinity PCR |
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