The amplification refractory mutation system (ARMS): A rapid and direct prenatal diagnostic technique for β-thalassaemia in Singapore

β-Thalassaemia major patients have chronic anaemia and since 3–4 per cent of Singaporeans carry the β-gene, prenatal diagnosis is essential. We evaluated the amplification refractory mutation system (ARMS) technique as a routine test for prenatal diagnosis of β-major. Six mutations along the β-gene were studied—41–42 (-TCTT), IVSII #654 (C-T), 17β (A-T), – 28 TATA (A-G), IVSI #5 (G-C), and IVSI #1 (G-T). Our results indicate that prenatal diagnosis using these mutations can be offered to 90 per cent (35/39) of our Chinese couples and 54·6 per cent (12/22) of our Malay couples at risk. Confirmation of ARMS results was carried out using allele-specific oligonucleotide hybridization. Prenatal diagnosis using ARMS was successfully carried out in nine cases which included a set of triplets and twins. The triplets were diagnosed with the β-trait carrying the 41–42 mutation. The couple with twins possessed the #654 mutation and one twin was diagnosed with the β-trait and the other with #654 homozygosity. Genomic sequencing of the undefined mutations in the Chinese couples revealed rarer mutations at − 29 and an ATG-AGG base substitution at the initiation codon for translation. In the Malay couples, genomic sequencing detected mutations at codon 15 (TGG-TAG) and codon 26 (GAG-AAG). We conclude that ARMS with its direct detection of amplified products by gel electrophoresis provides an accurate, rapid, and simpler method for our β-thalassaemia prenatal diagnosis programme in Singapore.