Molecular characterization of a novel 10.3 kb deletion causing β‐thalassaemia with unusually high Hb A2

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Abstract
A family of Asian-Indian descent has a variant form of β-thalassaemia characterized by unusually high levels of Hb A2 in the heterozygous state. The propositus who is homozygous for the mutation has thalassaemia intermedia. Restriction endonuclease mapping suggested the presence of a 10.3 kilobase (kb) deletion removing the whole of the β-globin gene. Subsequently, molecular analysis was performed by directly sequencing a specifically amplified region of genomic DNA. A 10329 basepair deletion was precisely defined which results in the loss of the 5’β promoter region and the entire β-globin gene. The deletion extends from 3011 bp 5’to the mRNA cap site to an L1 repeat element downstream of the β-globin gene and is very similar to the 12.6 kb deletion of Dutch β-thalassaemia. In common with four other mutations, both these deletions remove the 5’promoter region of the β gene and all are associated with unusually elevated levels of Hb A2 in the heterozygous state.