Molecular spectrum of α-thalassemia mutations in Erbil province of Iraqi Kurdistan

Abstract

α-Thalassemia is a globally prevalent genetic disorder of hemoglobin (Hb) structure where the rate of α-globin chain synthesis is reduced or absent based on the underlying α-globin mutation(s). This study aimed to define the spectrum of α-globin gene mutations and assess their relative frequency within a group of α-thalassemia carriers. A total of 96 young subjects with unexplained hypochromia and microcytosis were recruited. They were referred from the premarital hemoglobinopathy screening and genetic counseling center in Erbil. All subjects were genetically tested for 21 common α-globin gene mutations using multiplex PCR and reverse hybridization. Six different α-globin gene mutations and nine different genotypes were detected in 84 carrier subjects. Their mean Hb was 12.9 (± 1.29) g/dL, of whom 49 subjects (58.3%) had a normal Hb level. The two most frequently encountered mutations were -α^3.7 deletion (62.86%) and α2^−5nt mutation (20%). Deletions were encountered in 71.43% of the mutated alleles. The most commonly observed genotype was -α^3.7/αα (46.43%), followed by -α^3.7/-α^3.7 and α^−5ntα/αα genotypes (10.72% each). Carriers of α^poly-A1α/αα and -α^3.7/-α^−5ntα genotypes showed significantly lower Hb, mean cell volume, and mean cell Hb values comparing to carriers of most other genotypes. In our population, the spectrum of α-globin mutations was confined to a limited number of mutations with deletions being mostly observed.