Frequency of α-Globin Gene Triplications and Coinheritance with β-Globin Gene Mutations in the Iranian Population

Abstract

Numerical variation in α-globin genes is very important due to their roles as an effective factor for phenotype presentation. An unequal crossover from misalignment of a homologous sequence of an α-globin gene during meiosis can produce a numerical alteration. A single α-globin gene deletion is the most frequent mutation in α-thalassemia (α-thal) worldwide, while the additional α-globin chain is relatively common. The excess α-globin gene plays a critical role in pathophysiology of thalassemia, especially when in coinherited with β-thalassemia (β-thal). α-Globin triplication leads to an imbalanced ratio between α- and β-globin chains, thus, it can exacerbate the clinical and hematological features of β-thal. Different studies have been performed in various countries to determine the frequency of α-globin triplication and its genotype-phenotype correlation with β-thal. In this study, we focused on the frequency of α-globin gene triplication and its characterization, either solely or in coexistence with β-globin gene mutations in Iranian populations. We have investigated the α-globin gene rearrangements in 4010 individuals from different provinces of Iran with normal to abnormal hematological parameters. In total, the frequency of the αααanti 3.7 triplication was 1.7% and phenotype aggravation was observed in α-globin triplication patients who were carriers of β-thal. Therefore, identification of genotype-phenotype correlation of α-globin triplication with β-thal can be very useful for predicting the severity of clinical manifestations during genetic counseling.