Interaction of an α-Globin Gene Triplication with β-Globin Gene Mutations in Iranian Patients with β-Thalassemia Intermedia

The 3.7 kb triplicated alpha-globin gene (alpha alpha alpha(anti) (3.7)) mutation has been found in most populations. It results from an unequal crossover between misaligned homologous segments in the alpha-globin gene cluster during meiosis. The pathophysiology and clinical severity of beta-thalassemia (beta-thal) are associated with the degree of a chain imbalance. The excess of alpha-globin chains plays an important role in the pathophysiology of beta-thal. When heterozygous/homozygous beta-thal coexists with an alpha gene numerical alteration, the clinical and hematological phenotype of thalassemia could change to mild anemia in case of an alpha deletion (-alpha/alpha alpha) or severe anemia in the case of an alpha triplication (alpha alpha/alpha alpha). The coexistence of an alpha alpha alpha(anti 3.7) triplication is considered an important factor in the severity of beta-thal, exacerbating the phenotypic severity of beta-thal by causing more globin chain imbalance. This study shows that the alpha alpha alpha(anti 3.7) triplication is an important factor in the causation of beta-thal intermedia (beta-TI) in heterozygous beta-thal. This type of phenotype modification has rarely been observed and reported in the Iranian population. Here we report the coinheritance of a triplicated alpha-globin gene arrangement and heterozygous/homozygous beta-thal in 23 cases, presenting with a beta-TI or beta-thal major (beta-TM) phenotype. Some of these patients were considered to have a mild beta-TI phenotype as they needed no blood transfusions; some occasionally received blood transfusions in their lifetime (for example on delivery) but some are dependent on regular blood transfusions (every 20 to 40 days). Our study was focused on the importance of detecting the alpha-globin gene triplication in genotype/phenotype prediction in Iranian thalassemia patients.