Homozygosity for a Rare β⁰-Thalassemia Mutation [Frameshift Codons 25/26 (+T)] Causes β-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.

Prevalence of Xmnl Gγ polymorphism in Egyptian patients with β-thalassemia major

“… 6 The severity of β-thalassemia is remarkable for its variability in different populations, even in different patients. 13 The 158(C-T) polymorphism of the Gγ-globin gene (Xmnl polymorphism) is known to ameliorate the severity of the disease because of its strong association with an increased production of HbF. 2 , 3 HbF production can partially compensate for the lack of adult hemoglobin (HbA) in patients with β-thalassemia major or intermedia.…”

Rare and New Mutations of B-Globin in Azari Population of Iran, a Considerable Diversity

“…CD25/26, which originally is a Tunisian mutation, is among the rarest mutations in Iran. It was introduced by Haghi et al in 2009 in Tabriz, East Azerbaijan province, Iran ( 13 ). In this study, this mutation was identified in five out of 1541 subjects (0.33%).…”

“…In each province, some of these mutations are categorized as common, while others are known to be rare. Collectively, in the 30 provinces of Iran, 13 mutations encompass 70-90% of the patients with β-thalassemia these mutations are classified as common (4,8,(13)(14)(15)(16). The majority of the mutations are single nucleotide substitutions or point mutations.…”