This paper describes four families of Italian descent in each of which the propositus had the clinical phenotype of thalassaemia intermedia, resulting from the compound heterozygous state for high HbA2 β thalassaemia and type I silen β thalassaemia. Direct sequencing on amplified DNA and/or oligonucleotide analysis detected, in all families but one, the compound heterozygous state for codon 39 nonsense mutation and the C-T substitution at position -101 in the distal CACCC box of the β-globin gene promoter (β(th-101)). Members of these families who are heterozygous for high HbA2 β thalassaemia showed the codon 39 nonsense mutation, while those with the clinical phenotype of silent β thalassaemia had the β(th-101) mutation. In the remaining family, the propositus and one of his siblings had the compound heterozygous state for a molecularly undefined high HbA2 β thalassaemia and the β(th-101) mutation in combination with the triple α globin gene arrangement. These patients showed a more severe thalassaemia intermedia like clinical phenotype as compared to those with the same β-globin genotype and a normal α-globin gene arrangement. In the families investigated the β(th-101) was always associated with haplotype I. A group of patients with thalassaemia intermedia from Southern Italy, either homozygous or heterozygous for haplotype I and in whom previous studies had failed to define the mutation in one of the β thalassaemia globin genes, were screened by oligonucleotide analysis for the presence of the β(th-101). Three out of nine were positive. These results indicate that the β(th-101) mutation is a common cause of the type I silent β thalassaemia phenotype in the Southern Italian population.
|Number of pages||7|
|Journal||British Journal of Haematology|
|Publication status||Published - 1990|
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