Fisher, C.A.Premawardhena, A.P.de Silva, S.Perera, G.Rajapaksa, S.Olivieri, N.A.Old, J.M.Weatherall, D.J.Sri Lanka Thalassaemia Study Group2014-10-292014-10-292003British Journal of Haematology. 2003; 121(4): 662-710007-1048 (Print)1365-2141 (Electronic)http://repository.kln.ac.lk/handle/123456789/1565Indexed in MEDLINEThe beta-globin gene mutations and the alpha-globin genes of 620 patients with the phenotype of severe to moderate thalassaemia from seven centres in Sri Lanka were analysed. Twenty-four beta-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 CD10 inclusively, IVSI-129 (A-->C) in the consensus splice site, and a frame shift, CD55 (-A). The allele frequency of alpha+ thalassaemia was 6.5% and 1.1% for -alpha3.7 and -alpha4.2 deletions respectively. Non-deletion alpha-thalassaemia was not observed. Triplicate or quadruplicate alpha-globin genes were unusually common. In 1.5% of cases it was impossible to identify beta-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 alpha-globin gene together with beta-thalassaemia trait. These findings have implications for the control of thalassaemia in high-frequency populations with complex ethnic histories.Thalassemiaalpha-Thalassemia-epidemiologybeta-Thalassemia-epidemiologyalpha-Thalassemia-geneticsbeta-Thalassemia-geneticsSri Lanka-epidemiologyMutation-geneticsGlobins-geneticsArticleMedicine