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 A(2) 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 (-5nt)) (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.