A Novel Mutation in the α2-Globin Gene in Two Unrelated Iranian Families

Background: ?-globin is encoded by two adjacent genes, ?l and ?2. Evidence suggests that these genes are not expressed equally and that the ?2-globin gene encodes the majority of ?-globin. This finding predicts that a thalassemic mutation of the ?2-globin gene would result in a more severe loss of ?-chain synthesis than a similar mutation in the ?l-globin gene. Objectives: In the present study we described a novel non-deletion ?-thalassemia defect in the 5ʹUTR region of the ?2-globin gene. Materials and Methods: For molecular analysis, genomic DNA was isolated from peripheral blood cells by a salting out procedure. The common alpha deletion mutations were ruled out using the published primers and conditions. The amplification of the entire B and ?1 globin genes was also carried out and their DNA was sequenced. No mutation was detected. Results: The mutation under study was located on an AP-1 transcription factor binding site and inherited in two unrelated Iranian families with hypochromic microcytic anemia. Conclusions: The patients in this study had moderate microcytosis and hypochromia without hemolysis, jaundice and splenomegaly. Molecular analysis in these patients revealed a non-deletion type of mutation in the promoter region, which is highly consistent with findings of other studies.