title: The molecular basis of beta-thalassemia in Thailand: application to prenatal diagnosis.
abstract: To enable the prenatal diagnosis of beta-thalassemia by direct detection of the mutant beta-globin genes, we have determined the spectrum of mutations causing this disease in Thailand. The techniques employed included a combination of synthetic oligonucleotide probe hybridization, direct sequencing of genomic DNA enzymatically amplified by the polymerase chain reaction, and cloning and sequencing of the beta-globin genes. A total of 116 beta-thalassemia genes from 78 Hb E/beta-thalassemia patients and from 19 homozygous beta-thalassemia patients were analyzed, and the mutation was characterized in 112/116 (97%) of them. Eleven mutations were found, of which four (-CTTT in codon 41/42, AAG----TAG in codon 17, C----T in position 654 of the IVS-2 region, and A----G in position -28 upstream of the beta-globin gene) accounted for 83%; two previously undescribed mutations have been identified. The spectrum of beta-thalassemia mutations is similar to that reported among the Chinese. However, within the Thai population itself, patients with homozygous beta-thalassemia show a wider spread of mutations in comparison with the Hb E/beta-thalassemia group, in whom the frameshift 41/42 mutation predominates at a frequency of 62%. This difference in distribution may reflect the difference in ethnic origin of the two groups. Characterization of these mutations should aid the planning of a prenatal diagnosis program for beta-thalassemia in Thailand.
authors.affiliation: Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, England.
authors.forename: S L
authors.initials: SL
authors.lastname: Thein
authors.forename: P
authors.initials: P
authors.lastname: Winichagoon
authors.forename: C
authors.initials: C
authors.lastname: Hesketh
authors.forename: S
authors.initials: S
authors.lastname: Best
authors.forename: S
authors.initials: S
authors.lastname: Fucharoen
authors.forename: P
authors.initials: P
authors.lastname: Wasi
authors.forename: D J
authors.initials: DJ
authors.lastname: Weatherall
mesh_terms: D001483:Base Sequence; D003001:Cloning, Molecular; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis / Q000235:genetics*; D005796:Genes; D005914:Globins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis; D013785:Thailand; D013789:Thalassemia / Q000175:diagnosis / Q000235:genetics*
chemical_list: D015345:Oligonucleotide Probes; D005914:Globins