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

✍ Scribed by Ivy S. L. Ng; Joyce B. K. Ong; Cheng Lim Tan; Hai Yang Law

• Publisher: Springer
• Year: 1994
• Tongue: English
• Weight: 359 KB
• Volume: 94
• Category: Article
• ISSN: 0340-6717
• DOI: 10.1007/bf00201598

✦ Synopsis

The strategy for early prenatal diagnosis of [3thalassemia in Singapore by direct detection of the mutant 13-globin gene requires the spectrum of mutations producing the disorder in this population to be characterized. We analyzed 134 13-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 affected families.