Molecular characterization of β‐globin gene mutations in Malay patients with Hb E‐β‐thalassaemia and thalassaemia major

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Abstract
Summary. This study concerned the identification of the β-thalassaemia mutations that were present in 27 Malay patients with Hb E-β-thalassaemia and seven Malay patients with thalassaemia major who were from West Malaysia. Nearly 50% of all β-thalassaemia chromosomes carried the G → C substitution at nucleotide 5 of IVS-I; the commonly occurring Chinese anomalies such as the frameshift at codons 41 and 42, the nonsense mutation A → T at codon 17, the A → G substitution at position −28 of the promoter region, and the C → T substitution at position 654 of the second intron, were rare or absent. Two new thalassaemia mutations were discovered. The first involves a frameshift at codon 35 (-C) that was found in two patients with Hb E-β°-thalassaemia and causes a β°-thalassaemia because a stop codon is present at codon 60. The second is an AAC → AGC mutation in codon 19 that was present on six chromosomes. This substitution results in the production of an abnormal β chain (β-Malay) that has an Asn → Ser substitution at position β19. Hb Malay is a‘Hb Knossos-like’β+-thalassaemia abnormality; the A → G mutation at codon 19 likely creates an alternate splicing site between codons 17 and 18, reducing the efficiency of the normal donor splice site at IVS-I to about 60%.