Homozygosity for a Rare β0-Thalassemia Mutation [Frameshift Codons 25/26 (+T)] Causes β-Thalassemia Intermedia in an Iranian Family

Abstract

The severity of ?-thalassemia (?-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 ?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 ?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?-globin gene (XmnI marker) and two other polymorphisms in the A?-globin promoter at position +25 (G>A) and -588 (G>A). Deletions in the ?- and ?-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 ?-thal intermedia and highlight the importance of the regulation of hemoglobin (Hb) F production in the ?-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. Copyright آ© Informa Healthcare USA, Inc.