title: Molecular defects in the beta-globin gene identified in different ethnic groups/populations during prenatal diagnosis for beta-thalassemia: a Malaysian experience.
abstract: Beta-thalassemia is the most-common genetic disorder of hemoglobin synthesis in Malaysia, and about 4.5% of the population are heterozygous carriers of the disorder. Prenatal diagnosis was performed for 96 couples using the Amplification Refractory Mutation System and Gap-Polymerase Chain Reaction. We identified 17 beta-globin defects-initiation codon for translation (T-G), -29 (A-G), -28 (A-G), CAP +1 (A-C), CD 8/9 (+G), CD 15 (G-A), CD 17 (A-T), CD 19 (A-G), Hb E (G-A), IVS1-1 (G-T), IVS1-5 (G-C), CD 41/42 (-CTTT), CD 71-72 (+A), IVS2-654 (CT), poly A(A-G), 100-kb Ggamma(Agammadeltabeta) degrees and 45-kb Filipino deletions. The 192 beta-alleles studied comprised Chinese (151 patients), Malay (21), Orang Asli from East Malaysia (15), Filipino (1), Indian (1), Indonesian Chinese (2), and Thai (1). In the Chinese, 2 beta-globin defects at CD 41/42 and IVS2-654 were responsible for 74% of beta-thalassemia. beta-mutations at CD 19, IVS1-1 (G-T), IVS1-5, poly A, and hemoglobin E caused 76% of the hemoglobin disorders in the Malays. The Filipino 45-kb deletion caused 73.3% of bthalassemia in the Orang Asli. Using genomic sequencing, the rare Chinese beta-mutation at CD 43 (G-T) was confirmed in 2 Chinese, and the Mediterranean mutation IVS1-1 (G-A) was observed in a Malay beta-thalassemia carrier. The beta-globin mutations confirmed in this prenatal diagnosis study were heterogenous and 65 (68%) couples showed a different globin defect from each other. The use of specific molecular protocols has allowed rapid and successful prenatal diagnosis of beta-thalassemia in Malaysia.
authors.affiliation: Department of Molecular Medicine, University of Malaya Medical Centre (UMMC), 50603, Kuala Lumpur, Malaysia. jamatan@hotmail.com
authors.forename: J A M A
authors.initials: JA
authors.lastname: Tan
authors.forename: E
authors.initials: E
authors.lastname: George
authors.forename: K L
authors.initials: KL
authors.lastname: Tan
authors.forename: T
authors.initials: T
authors.lastname: Chow
authors.forename: P C
authors.initials: PC
authors.lastname: Tan
authors.forename: J
authors.initials: J
authors.lastname: Hassan
authors.forename: P
authors.initials: P
authors.lastname: Chia
authors.forename: R
authors.initials: R
authors.lastname: Subramanium
authors.forename: R
authors.initials: R
authors.lastname: Chandran
authors.forename: S F
authors.initials: SF
authors.lastname: Yap
mesh_terms: D044466:Asian People / Q000235:genetics*; D015193:Chorionic Villi Sampling; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics*; D005315:Fetal Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D005914:Globins / Q000235:genetics*; D006801:Humans; D008296:Malaysia / Q000453:epidemiology; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011296:Prenatal Diagnosis; D017086:beta-Thalassemia / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*
chemical_list: D005914:Globins