A NOVEL POLYADENYLATION SIGNAL MUTATION IN THE ALPHA(2)-GLOBIN GENE CAUSING ALPHA-THALASSEMIA

In a family of Indian origin we have identified a deletion of two bases at the polyadenylation signal sequence of the alpha(2)-globin gene (AATAAA --> AATA). Three individuals heterozygous for this mutation display an alpha degrees-thalassaemia-like phenotype. Single-stranded conformation analysis and automatic sequencing showed no additional mutations in either alpha(1)- or alpha(2)-globin genes. A previously described polyadenylation sequence mutation (AATAAA --> AATAAG), alpha(TSaudi)alpha, causes HbH disease in homozygotes. In this study the patients heterozygous for the AATA(-AA) mutation show a similar phenotype observed in the alpha(TSaudi)alpha heterozygotes. This confirms the observation that the inefficient transcriptional termination due to mutations of the polyadenylation sequence of the alpha(2)-gene might interfere with the alpha(1)-gene expression.