Interaction of heterozygous βo‐thalassemia with single functional α‐globin gene

In this study, we analyzed the phenotypic manifestations resulting from the interaction of heterozygous βo‐thalassemia(βo‐39 nonsense mutation) with the functional loss of three α‐globin structural genes in six subjects, of whom four had the [‐αl–] α‐globin genotype and two the [–/αThα] α‐globin genotype. The β‐thalassemia defect was in all cases the nonsense mutation at codon 39. The nondeletion α‐thalassemia αth was the initiation codon mutation (AUG→GUG) of the α‐2 gene. In all these subjects hypochromia and microcytosis were more marked than in βα ‐thalassemia heterozygotes with a full complement of four α‐globin genes. All but one had moderate anemia. The α:β globin chain synthesis ratios were consistently decreased. No cases had Hb H on electrophoresis. Subjects with [–/αThα] α‐globin genotype had more severe thalassemia‐like manifestations than those with [–/‐α] α‐globin genotype.