title: Transfusion-dependent thalassemia in Northern Sarawak: a molecular study to identify different genotypes in the multi-ethnic groups and the importance of genomic sequencing in unstudied populations.
abstract: BACKGROUND
  Although thalassemia is a genetic hemoglobinopathy in Malaysia, there is limited data on thalassemia mutations in the indigenous groups. This study aims to identify the types of globin gene mutations in transfusion-dependent patients in Northern Sarawak.
  
  
  METHODS
  Blood was collected from 32 patients from the Malay, Chinese, Kedayan, Bisayah, Kadazandusun, Tagal, and Bugis populations. The α- and β-globin gene mutations were characterized using DNA amplification and genomic sequencing.
  
  
  RESULTS
  Ten β- and 2 previously reported α-globin defects were identified. The Filipino β-deletion represented the majority of the β-thalassemia alleles in the indigenous patients. Homozygosity for the deletion was observed in all Bisayah, Kadazandusun and Tagal patients. The β-globin gene mutations in the Chinese patients were similar to the Chinese in West Malaysia. Hb Adana (HBA2:c.179G>A) and the -α(3.7)/αα deletion were detected in 5 patients. A novel 24-bp deletion in the α2-globin gene (HBA2:c.95 + 5_95 + 28delGGCTCCCTCCCCTGCTCCGACCCG) was identified by sequencing. Co-inheritance of α-thalassemia with β-thalassemia did not ameliorate the severity of thalassemia major in the patients.
  
  
  CONCLUSIONS
  The Filipino β-deletion was the most common gene defect observed. Homozygosity for the Filipino β-deletion appears to be unique to the Malays in Sarawak. Genomic sequencing is an essential tool to detect rare genetic variants in the study of new populations.
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Jin-Ai M A
authors.initials: JA
authors.lastname: Tan
authors.forename: Saw-Sian
authors.initials: SS
authors.lastname: Chin
authors.forename: Gek-Bee
authors.initials: GB
authors.lastname: Ong
authors.forename: Mohamed N
authors.initials: MN
authors.lastname: Mohamed Unni
authors.forename: Ashley E R
authors.initials: AE
authors.lastname: Soosay
authors.forename: Henry R
authors.initials: HR
authors.lastname: Gudum
authors.forename: Siew-Leng
authors.initials: SL
authors.lastname: Kho
authors.forename: Kek-Heng
authors.initials: KH
authors.lastname: Chua
authors.forename: Jang J
authors.initials: JJ
authors.lastname: Chen
authors.forename: Elizabeth
authors.initials: E
authors.lastname: George
mesh_terms: D001483:Base Sequence; D001803:Blood Transfusion / Q000379:methods*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D006453:Hemoglobinopathies / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000032:analysis; D006720:Homozygote; D006801:Humans; D008296:Malaysia / Q000453:epidemiology; D008297:Male; D009154:Mutation; D044382:Population Groups / Q000208:ethnology / Q000235:genetics; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000453:epidemiology / Q000235:genetics / Q000628:therapy
chemical_list: D006455:Hemoglobins, Abnormal; D055544:beta-Globins; C083925:hemoglobin Adana