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 ααα^{anti 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.

Keywords:

• α-Thalassemia (α-thal)
• α-globin gene triplication
• β-thalassemia (β-thal)
• blood transfusion
• Iranian population

Acknowledgments

The authors are grateful to all technical assistants at the Molecular Department of Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran, for their collaboration in this research, and we also thank the patients and their families who participated in this study.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.