title: Molecular study and genotype/phenotype correlation of β Thalassemia in Malaysia.
abstract: BACKGROUND
  To study the ß-gene mutations spectrum, the genotype/phenotype correlation, the modulatory effect of co-inherited factors such as α-gene mutations and of Xmn1 polymorphism in a large cohort of Malaysian patients.
  
  
  METHODS
  A total of 264 cases clinically diagnosed as Thalassemia major (TM) (111), Thalassemia intermedia (21), HbE-β Thalassemia (131), and 1 HbE homozygous were studied. The detection of α and ß gene mutations and characterization of Xmn1 polymorphism were performed by multiplex PCR, amplification refractory mutation system (ARMS), DNA sequencing, and restriction fragment length polymorphism (RFLP)-PCR.
  
  
  RESULTS
  A total of 19 ß Thalassemia mutations were characterized. CD26 and CD41/42 were the most common found in the Malay and Chinese population, respectively. The sensitivity of the clinical diagnosis for β TM, thalassemia intermedia, and HbE/β thalassemia was 94.0%, 15.2%, and 89.2%, respectively. Patients with Xmn1 heterozygosity [+/-] required less frequent transfusion compared with those without the polymorphism. Co-inheritance of α-thalassemia alleviates the severity of HbE-β thalassemia in our cohort.
  
  
  CONCLUSIONS
  Molecular analysis should be used for a better diagnosis and management of β thalassemia.
authors.affiliation: UKM Medical Molecular Biology Institute (UMBI), Kuala Lumpur, Cheras, Malaysia.
authors.forename: M
authors.initials: M
authors.lastname: Sivalingam
authors.forename: M L
authors.initials: ML
authors.lastname: Looi
authors.forename: S Z S
authors.initials: SZ
authors.lastname: Zakaria
authors.forename: N H
authors.initials: NH
authors.lastname: Hamidah
authors.forename: H
authors.initials: H
authors.lastname: Alias
authors.forename: Z A
authors.initials: ZA
authors.lastname: Latiff
authors.forename: H
authors.initials: H
authors.lastname: Ibrahim
authors.forename: R
authors.initials: R
authors.lastname: Jamal
mesh_terms: D044466:Asian People; D017353:Gene Deletion; D056726:Genetic Association Studies; D006801:Humans; D007194:India; D008296:Malaysia; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D055544:beta-Globins