Identification of Mutations Causing Aberrant Termination and Deficient Splice Donor Site on the HBA1 Gene

Abstract

α-Thalassemia (α-thal) is a common genetic disorder in Iran and many parts of the world. Genetic defects on the α-globin gene cluster can result in α-thal that may develop a clinical phenotype varying from almost asymptomatic to a lethal hemolytic anemia. In the present study, four Iranian individuals with hypochromic microcytic anemia, who revealed none of the known mutations responsible for α-thal, were subjected for further investigations. The thalassemic phenotype of these patients resulted from abnormal RNA splicing sites owing to a missense at the splice donor site, a truncated protein or hemoglobin (Hb) variants as a result of two different substitutions on the α1-globin gene. The clinical presentation of mild anemia in these individuals showed the contribution of these novel mutations in α-thal in spite of the dominantly expressed α2-globin gene. This study describes hematological manifestations of subjects carrying some novel mutations comparable to the reported phenotype of α⁺-thal trait.

• α-Thalassemia (α-thal)
• hypochromic microcytic anemia
• RNA splicing sites
• truncated protein

Acknowledgements

We thank all our colleagues at the Department of Molecular Genetics, Kariminejad-Najmabadi Pathology and Genetics Centre, Tehran, Iran for valuable technical assistance and also appreciate the cooperation of all the patients who took part in this study.

Declaration of interest

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