β-Thalassemia mutations in Singapore — a strategy for prenatal diagnosis

摘要

The strategy for early prenatal diagnosis of β-thalassemia in Singapore by direct detection of the mutant β-globin gene requires the spectrum of mutations producing the disorder in this population to be characterized. We analyzed 134 β-thalassemia alleles from Singapore by specific oligonucleotide hybridization after DNA amplification, using a nonradioactive enhanced chemiluminescence detection system. The mutations were identified in 90 of the alleles using five oligonucleotide probes for the following mutations: codons 41/42 (deletion -TCTT), IVS II nt 654 (C→T), codon 17 (A→T), IVS I nt 5 (G→C), and -28 TATA box (A→G). Together with the strategy of direct sequencing, a total of 97 of the mutations were identified. In the Chinese subpopulation, 97 of the mutations were detected by the oligonucleotide probes. Using just four oligonucleotide probes would identify 96 of the mutations, and 76 of the mutations were accounted for by codon 41/42 (-TCTT) and IVS II nt 654 (C→T) mutations. Thus in this subpopulation early prenatal diagnosis would be possible in virtually all the affec