The molecular basis for the thalassaemias in Sri Lanka

Abstract

The β-globin gene mutations and the α-globin genes of 620 patients with the phenotype of severe to moderate thalassaemia from seven centres in Sri Lanka were analysed. Twenty-four β-globin gene mutations were identified, three accounting for 84.5% of the 1240 alleles studied: IVSI-5 (G → C) 56.2%: IVSI-1 (G → A) 15.2%; and haemoglobin E (codon (CD)26 GAG → GAA) 13.1%. Three new mutations were found: a 13-bp deletion removing the last nucleotide in CD6 to CD1O inclusively, IVSI-129 (A → C) in the consensus splice site, and a frame shift. CD55 (-A). The allele frequency of α+ thalassaemia was 6.5% and 1.1% for -α3.7 and -α4.2 deletions respectively. Non-deletion α-halassaemia was not observed. Triplicate or quadruplicate α-globin genes were unusually common. In 1.5% of cases it was impossible to identify β-thalassaemia alleles, but in Kurunegala detailed family studies led to an explanation for the severe thalassaemia phenotype in every case, including a previously unreported instance of homozygosity for a quadruplicated α-globin gene together with β-thalassaemia trait. These findings have implications for the control of thalassaemia in high-frequency populations with complex ethnic histories.