title: A single, large deletion accounts for all the beta-globin gene mutations in twenty families from Sabah (North Borneo), Malaysia. Mutation in brief no. 240. Online.
abstract: Beta-thalassemia major is one of the commonest genetic disorders in South-East Asia. The spectrum of beta-thalassemia mutations in the various ethnic sub-populations on the island of Borneo is unknown. We studied 20 Dusun children from the East Malaysian state of Sabah (North Borneo) with a severe beta-thalassemia major phenotype, using a combination of Southern analysis, polymerase chain reaction analysis and direct sequencing. We found the children to be homozygous for a large deletion, which has a 5' breakpoint at position -4279 from the cap site of the beta-globin gene (HBB) with the 3' breakpoint located in a L1 family of repetitive sequences at an unknown distance from the beta-globin gene. This was similar to a recent finding of a large deletion causing beta-thalassemia first described in unrelated beta-thalassemia heterozygotes of Filipino descent. This report describes the first 20 families with homozygosity of the deletion causing a severe phenotype. It provides the first information on the molecular epidemiology of beta-thalassemia in Sabah. This finding has implications for the population genetics and preventative strategies for beta-thalassemia major for nearly 300 million individuals in South-East Asia.
authors.affiliation: Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. thongmk@mail.wch.sa.gov.au
authors.forename: M K
authors.initials: MK
authors.lastname: Thong
authors.forename: Z
authors.initials: Z
authors.lastname: Rudzki
authors.forename: J
authors.initials: J
authors.lastname: Hall
authors.forename: J A
authors.initials: JA
authors.lastname: Tan
authors.forename: L L
authors.initials: LL
authors.lastname: Chan
authors.forename: S F
authors.initials: SF
authors.lastname: Yap
mesh_terms: D015139:Blotting, Southern; D017353:Gene Deletion; D005914:Globins / Q000235:genetics*; D006801:Humans; D008296:Malaysia; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D005914:Globins