Heterozygosity for the Novel HBA2: c.*91_*92delTA Polyadenylation Site Variant on the α2-Globin Gene Expanding the Genetic Spectrum of α-Thalassemia in Iran

Abstract

There are four copy numbers of α-globin genes (16p13.3) in the human genome and the number of defective α-globin genes dictates the severity of α-thalassemia (α-thal). Mutations that occur in the 3′ untranslated region (3′UTR), and especially at the polyadenylation (polyA) sites, affect the translation, stability and export of mRNA. A patient with hypochromic microcytic anemia was referred to the Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran by the health network. Molecular analysis of genomic DNA for the evaluation of mutations on the α- and β-globin genes was performed. Direct sequencing of the hemoglobin (Hb) subunit α2 (HBA2) gene revealed a two nucleotide deletion between +816 and +817 in the 3′UTR, located at the polyA site, which seems to be a novel pathogenic variant. This novel variant expands the genetic spectrum of α-thal in the 3′UTR of the HBA2 gene.

Keywords:

• α-Thalassemia (α-thal)
• hemoglobin (Hb) subunit α2 (HBA2)
• Hb subunit α1 (HBA1)
• hypochromic microcytic anemia
• polyadenylation (polyA)

Acknowledgments

We are grateful to all our colleagues at the Molecular Department of the Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran, for valuable technical assistance and also appreciate the cooperation of all the patients who took part 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.