The molecular basis of thalassaemia major and thalassaemia intermedia in Asian Indians: application to prenatal diagnosis

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Abstract
A study of the molecular pathology of β thalassaemia in the Asian Indian immigrant population in the U.K. included 37 patients with thalassaemia major and 14 with thalassaemia intermedia. Using a combination of oligonucleotide probe hybridization and restriction endonuclease analysis the mutations in 100/102 (98%) of the β thalassaemia genes were characterized. Nine different types were found, of which six are associated with β, one with severe β+ and two with mild β+ thalassaemia. Comparison of the β-globin gene cluster haplotypes, α globin genotypes and β gene mutations of the thalassaemia major group with the thalassaemia intermedia group suggests that the co-inheritance of a high Hb F determinant associated with the - + - ++ 5’β haplotype and the inheritance of a mild β-thalassaemia mutation are the major ameliorating factors of disease severity in Asian Indians. In comparison with other population groups, β thalassaemia in Asian Indians is not associated with one or two predominant mutations. Despite this, prenatal diagnosis by direct detection is possible in the majority of families by restriction analysis and a limited number of oligonucleotide probes since the majority of severely affected individuals are homozygous for a single mutation. The characterization of these mutations should be useful for the planning of prenatal diagnosis programmes for β thalassaemia in other Asian Indian communities.