The spectrum of β-thalassemia mutations in Malays in Singapore and Kelantan

Abstract

The spectrum of β-thalassemia mutations in Malays in Singapore and Kelantan (Northeast Malaysia) was studied. Allele specific priming was used to determine the mutations in β-carriers at -28, Codon 17, IVSI #1, IVSI #5, Codon 41-42 and IVSII #654 along the β-globin gene. The most common structural hemoglobin variant in Southeast Asia, Hb E, was detected by DNA amplification with restriction enzyme (Mnl1) analysis. Direct genomic sequencing was carried out to detect the β-mutations uncharacterized by allele-specific priming. The most prevalent β-mutations in Singaporean Malays were IVSI #5 (45.83%) followed by Hb E (20.83%), codon 15 (12.5%) and IVSI #1 and IVSII #654 at 4.17% each. In contrast, the distribution of the β-mutations in Kelantan Malays differed, with Hb E as the most common mutation (39.29%) followed by IVSI #5 (17.86%), codon 41-42 (14.29%), codon 19 (10.71%) and codon 17 (3.57%). The β-mutations in Kelantan Malays follow closely the distribution of β-mutations in Thais and Malays of Southern Thailand and Malays of West Malaysia. The AAC →AGC base substitution in codon 19 has been detected only in these populations. The spectrum of β-mutations in the Singaporean Malays is more similar to those reported in Indonesia with the β-mutation at codon 15 (TGG→TAG) present in both populations. The characterization of β-mutations in Singaporean and Kelantan Malays will facilitate the establishment of effective prenatal diagnosis programs for β-thalassemia major in this ethnic group.