Molecular characterization of beta-thalassaemia in Singaporean Chinese: application to prenatal diagnosis

Sixty-five beta-thalassaemia genes from 14 unrelated Chinese beta-thalassaemia major patients and 37 Chinese beta-carriers were analysed by allele-specific oligonucleotide (ASO) hybridization after DNA amplification by the polymerase chain reaction (PCR). Six mutations were studied and are represented by 49.2% of codon 41-42, 30.8% of IVSII #654, 6.2% of 17 beta, 3.1% of IVSI #5 (G-->C) and 1.5% of -28 TATA box. The complete mutations responsible for beta-thalassaemia major in 13 of our 14 affected families were identified. For these families prenatal diagnosis at 10 weeks gestation using DNA amplification and ASO hybridization will replace the globin chain biosynthesis technique at 19 weeks gestation. Using ASO analysis, our results indicate that 5 oligo-probes (41-42, II-#654, 17 beta, IVSI-#5 and -28) allow determination of beta-thalassaemia mutations in 59/65 (90.8%) of the Singaporean Chinese studied.