THE AMPLIFICATION REFRACTORY MUTATION SYSTEM (ARMS) - A RAPID AND DIRECT PRENATAL DIAGNOSTIC-TECHNIQUE FOR BETA-THALASSEMIA IN SINGAPORE

beta-Thalassaemia major patients have chronic anaemia and since 3-4 pe r cent of Singaporeans carry the beta-gene, prenatal diagnosis is esse ntial. We evaluated the amplification refractory mutation system (ARMS ) technique as a routine test for prenatal diagnosis of beta-major. Si x mutations along the beta-gene were studied-41-42 (-TCTT), IVSII #654 (C-T), 17 beta (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 re sults was carried out using allele-specific oligonucleotide hybridizat ion. Prenatal diagnosis using ARMS was successfully carried out in nin e cases which included a set of triplets and twins. The triplets were diagnosed with the beta-trait carrying the 41-42 mutation. The couple with twins possessed the #654 mutation and one twin was diagnosed with the beta-trait and the other with #654 homozygosity. Genomic sequenci ng of the undefined mutations in the Chinese couples revealed rarer mu tations at -29 and an ATG-AGG base substitution at the initiation codo n for translation. In the Malay couples, genomic sequencing detected m utations at codon 15 (TGG-TAG) and codon 26 (GAG-AAG). We conclude tha t ARMS with its direct detection of amplified products by gel electrop horesis provides an accurate, rapid, and simpler method for our beta-t halassaemia prenatal diagnosis programme in Singapore.