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

• Published in: Hemoglobin Vol. 40; no. 1; pp. 38 - 43
• Main Authors: Farashi, Samaneh, Vakili, Shadi, Garous, Negin F., Ashki, Mehri, Forouzesh Pour, Fatemeh, Zeinali, Fatemeh, Rad, Fariba, Imanian, Hashem, Azarkeivan, Azita, Najmabadi, Hossein
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02.01.2016
• Subjects: Adult; alpha-Globins - genetics; alpha-Thalassemia - genetics; Anemia, Hypochromic - genetics; Base Sequence; Female; Genes, Dominant; Glycated Hemoglobin A - genetics; Humans; hypochromic microcytic anemia; Male; Molecular Sequence Data; Mutation; RNA Splice Sites; RNA splicing sites; truncated protein; α-Thalassemia (α-thal); RNA splicing sites; α-Thalassemia (α-thal); truncated protein; hypochromic microcytic anemia
• ISSN: 0363-0269; 1532-432X; 1532-432X
• DOI: 10.3109/03630269.2015.1088456

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.