Promoter mutations producing mild β‐thalassaemia in the Italian population

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Abstract
Summary. In this study we have investigated the molecular basis for a mild form of β‐thalassaemia in three patients of Italian descent. In two, belonging to different families and affected by a mild and late‐presenting form of thalassaemia major, direct sequencing of amplified DNA detected a C→T substitution at position −87 of the β‐globin gene in the compound heterozygous state either with codon 39 nonsense mutation or β+IVSI, nt 110 mutation. The −87 (C→T) mutation has been previously described, in combination with the β+IVSI, nt 110 mutation, in a single patient with thalassaemia intermedia. Both our patients showed a more severe phenotype as compared to that resulting from compound heterozygosity for a severe β‐thalassaemia mutation and another promoter mutation (−87, C→G) at the same position. In the third patient with the thalassaemia intermedia phenotype, we detected a novel promoter mutation, consisting in a C→A substitution at position −86, in combination with the codon 39 nonsense mutation. The results of this study indicate that different nucleotide substitutions affecting the proximal CACCC box of the β‐globin gene in combination with severe β‐thalassaemia, produce a mild form of thalassaemia ranging in severity from thalassaemia intermedia to late‐presenting thalassaemia major.

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