• β-thalassaemia;
  • α-thalassaemia;
  • mutations;
  • Sri Lanka

Summary. 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[RIGHTWARDS ARROW]C) 56·2%; IVSI-1 (G[RIGHTWARDS ARROW]A) 15·2%; and haemoglobin E (codon (CD)26 GAG[RIGHTWARDS ARROW]GAA) 13·1%. Three new mutations were found; a 13-bp deletion removing the last nucleotide in CD6 to CD10 inclusively, IVSI-129 (A[RIGHTWARDS ARROW]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-thalassaemia 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.