title: The molecular basis for the thalassaemias in Sri Lanka.
abstract: The 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.
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK. david.weatherall@imm.ox.ac.uk
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Fisher
authors.forename: Anuja
authors.initials: A
authors.lastname: Premawardhena
authors.forename: Shanthimala
authors.initials: S
authors.lastname: de Silva
authors.forename: Giathra
authors.initials: G
authors.lastname: Perera
authors.forename: Shabna
authors.initials: S
authors.lastname: Rajapaksa
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Olivieri
authors.forename: John M
authors.initials: JM
authors.lastname: Old
authors.forename: David J
authors.initials: DJ
authors.lastname: Weatherall
mesh_terms: D015139:Blotting, Southern; D005787:Gene Frequency; D005914:Globins / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D013188:Sri Lanka / Q000453:epidemiology; D017085:alpha-Thalassemia / Q000453:epidemiology* / Q000235:genetics; D017086:beta-Thalassemia / Q000453:epidemiology* / Q000235:genetics
chemical_list: D005914:Globins