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

Abstract

The severity of β-thalassemia (β-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 β⁰-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 β⁰ type and the affected members were dependent and independent of blood transfusions. This mutation was linked to the –158 (C>T) polymorphism on the ^Gγ-globin gene (XmnI marker) and two other polymorphisms in the ^Aγ-globin promoter at position +25 (G>A) and –588 (G>A). Deletions in the α- and β-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 β-thal intermedia and highlight the importance of the regulation of hemoglobin (Hb) F production in the β-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.

Keywords:

• β⁰-Thalassemia (β⁰-thal) mutation
• Frameshift codons (FSC) 25/26 (+T)
• XmnI marker