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.