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An initiation codon mutation as a cause of beta-thalassemia in a Belgian family.

par Wildmann, C;Larondelle, Y;Vaerman, J L;Eeckels, R;Martiat, Philippe ;Philippe, M
Référence Hemoglobin, 17, 1, page (19-30)
Publication Publié, 1993-02

Article révisé par les pairs

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Résumé :

Nine asymptomatic members of a family of Belgian origin, spanning three generations, present typical features of heterozygous beta-thalassemia. Since no mutation was detected with a large panel of oligonucleotide probes, the thalassemia gene was investigated by direct sequencing of DNA segments amplified by the polymerase chain reaction. A T-->C transition was detected in the translation initiation codon (ATG). The mutation, which abolishes an Nco I restriction site, was further confirmed by enzymatic digestion as well as by dot-blot hybridization of the amplified products with allele-specific oligonucleotide probes. It produced a beta zero-thalassemia phenotype characterized by marked microcytosis and hypochromia, as well as by an in vitro beta/alpha chain synthesis ratio close to O.5. Search for haplotype linkage showed the mutation to be associated with haplotype IX [- + - + + + +].