title: Characterisation and confirmation of rare beta-thalassaemia mutations in the Malay, Chinese and Indian ethnic groups in Malaysia.
abstract: OBJECTIVE
  In Malaysia, about 4.5% of the Malay and Chinese populations are heterozygous carriers of beta-thalassaemia. The initial identification of rare beta-globin gene mutations by genomic sequencing will allow the development of simpler and cost-effective PCR-based techniques to complement the existing amplification refractory mutation system (ARMS) and gap-PCR used for the identification of beta-thalassaemia mutations.
  
  
  METHODS
  DNA from 173 beta-thalassaemia carriers and five beta-thalassaemia major patients from the Malay, Chinese and Indian ethnic groups were first analysed by ARMS and gap-PCR. Ninety-five per cent (174/183) of the 183 beta-globin genes studied were characterised using these two techiques. The remaining nine uncharacterised beta-globin genes (4.9%) were analysed using genomic sequencing of a 904 bp amplified PCR product consisting of the promoter region, exon 1, intervening sequence (IVS) 1, exon 2 and the 5' IVS2 regions of the beta-globin gene.
  
  
  RESULTS
  The rare beta-globin mutations detected in the Chinese patients were CD27/28 (+C) and CD43 (GAG-TAG), and -88 (C-T) in an Indian patient. Beta-globin mutations at CD16 (-C), IVS1-1 (G-A), IVS2-1 (G-A), -86 (C-G) and Haemoglobin South Florida (CD1, GTG-ATG) were confirmed in the Malay patients.
  
  
  CONCLUSIONS
  The seven rare beta-globin mutations and a rare haemoglobin variant confirmed in this study have been described in other populations but have not been previously described in Malaysian beta-thalassemia patients.
authors.affiliation: Departments of Molecular Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia. jamatan@hotmail.com
authors.forename: Jin Ai Mary Anne
authors.initials: JA
authors.lastname: Tan
authors.forename: Pui See
authors.initials: PS
authors.lastname: Chin
authors.forename: Yean Ching
authors.initials: YC
authors.lastname: Wong
authors.forename: Kim Lian
authors.initials: KL
authors.lastname: Tan
authors.forename: Lee Lee
authors.initials: LL
authors.lastname: Chan
authors.forename: Elizabeth
authors.initials: E
authors.lastname: George
mesh_terms: D044466:Asian People / Q000235:genetics*; D002681:China / Q000208:ethnology; D004252:DNA Mutational Analysis; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007194:India / Q000208:ethnology; D008296:Malaysia / Q000453:epidemiology; D009154:Mutation; D016133:Polymerase Chain Reaction; D017086:beta-Thalassemia / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology