Homozygosity for a rare beta 0-thalassemia mutation [frameshift codons 25/26 (+T)] causes beta-thalassemia intermedia in an Iranian family

Abstract

The severity of beta-thalassemia (beta-thal) is remarkable for its variability in different populations, even in different patients. We studied a family from Azerbaijan Province, Northwestern Iran, who had a rare beta(0)-thal mutation, namely the frameshift codons (FSC) 25/26 (+T), originally reported in Tunisia. Unlike the Tunisian family, in our family the mutation was a beta(0) type and the affected members were dependent and independent of blood transfusions. This mutation was linked to the -158 (C>T) polymorphism on the (G)gamma-globin gene (XmnI marker) and two other polymorphisms in the (A)gamma-globin promoter at position +25 (G>A) and -588 (G>A). Deletions in the alpha- and beta-globin gene clusters were excluded in all samples. This is the first description of the FSC 25/26 mutation in Iran. The results of this study emphasize the complexity of genetic interactions that underlie the phenotype of beta-thal intermedia and highlight the importance of the regulation of hemoglobin (Hb) F production in the beta-thal syndromes. Simultaneous inheritance of some loci that interfere with the elevation of Hb F probably caused them to have high levels of total Hb and to be transfusion independent.