Molecular Study of Deletional and Nondeletional Mutations on the ?-Globin Locus in the Azeri Population of Northwestern Iran

Abstract

The aim of this study was to determine the molecular spectrum and frequency of deletional and nondeletional ?-thalassemia (?-thal) mutations and the genotype-phenotype correlation in common mutations in the Azeri population of Northwestern Iran. A total of 1256 potential carriers with microcytic and hypochromic anemia and normal Hb A2 levels (<3.5%) and without iron deficiency anemia plus three fetuses were identified. Multiplex gap-polymerase chain reaction (gap-PCR) and sequencing for ?-thal mutations were carried out. In 606 individuals, the ?-globin gene was normal, but in 650 persons (51.6%) and three fetuses, 10 different mutations were detected. The most frequent deletional genotypes were as follows: ??/-?3.7 (61.7%), -?3.7/-?3.7 (11.9%), ??/-?4.2 (4.6%), ??/- -MED (4.3%) and ??/-(?)20.5 (3.8%). The most frequent nondeletional genotypes were ??/?IVS-I (-5 nt)? (HBA2: c.95+2_95+6delTGAGG) and ??/?Poly A2? [polyadenylation signal (polyA2) (AATAAA>AATGAA); HBA2: c.*96G>A] with frequencies of 1.08% and 0.92%, respectively. Meanwhile, 7.71% of individuals with a proven ?-thalassemia (?-thal) mutation were found to also carry an ?-thal mutation. Persons having two functional ?-globin genes showed lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) values compared to those with one mutated ?-globin gene, provided that they had normal ?-globin genes. Overall, the incidence of ?-thal was 2.7% in the Azeri population in Northwestern Iran. Our results showed that the variability of ?-thal mutations are high in the Azeri population and that ?-thal mutations are highly heterogeneous in both deletional and nondeletional genotype aspects. © 2016 Informa UK Limited, trading as Taylor & Francis Group.