Molecular Study of Deletional and Nondeletional Mutations on the α-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 α-thalassemia (α-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 levels (<3.5%) and without iron deficiency anemia plus three fetuses were identified. Multiplex gap-polymerase chain reaction (gap-PCR) and sequencing for α-thal mutations were carried out. In 606 individuals, the α-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: αα/-α (61.7%), -α/-α (11.9%), αα/-α (4.6%), αα/- - (4.3%) and αα/-(α) (3.8%). The most frequent nondeletional genotypes were αα/αα (HBA2: c.95+2_95+6delTGAGG) and αα/αα [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 β-thalassemia (β-thal) mutation were found to also carry an α-thal mutation. Persons having two functional α-globin genes showed lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) values compared to those with one mutated α-globin gene, provided that they had normal β-globin genes. Overall, the incidence of α-thal was 2.7% in the Azeri population in Northwestern Iran. Our results showed that the variability of α-thal mutations are high in the Azeri population and that α-thal mutations are highly heterogeneous in both deletional and nondeletional genotype aspects.

Study of type and frequency of Alfa-thalassemia mutations in a cohort of 3,823 patients from Isfahan Province, Iran

“…So, the present study aimed to evaluate the α-globin mutations in the Isfahan Province, Iran. In concordance with the other studies performed on the different Iranian sub-populations, the -α 3.7 deletion was found to be the most prevalent α-thalassemia mutation in carrier individuals of Isfahan (81.58% of all 3,823 studied subjects) [16,20,22,25,28,30,31,[35][36][37][38]. The high prevalence of α 3.7 deletion mutation may be due to the high consanguinity rate among the Iranian population.…”

“…Based on the present findings, the -α 5nt deletion (39.01% out of all 364 patients with mutations other than -α 3.7 ) was the second most frequent mutation that is in concordance with the study performed on the neighbouring provinces including Hamadan (10.06%), Sistan and Baluchestan (16.77%), Lorestan (15.47%), Tehran (14.40%), Fars (8.26%), Kohgiluyeh and Boyer Ahmad (7.00%), and Kerman (5.7%) [7,16,18,20,26,27,30]. However, the reported allele frequencies in different provinces were different which may be due to the sub-population diversity (Table 1) [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28].…”

“…Deletion of -α codon19 (GCG4GC-) (α2) in Fars as a neighbouring province (3.92%) was also reported as the fourth mutation [21]. It is important to note that this mutation has not been reported in the studies performed in Lorestan, Golestan, and Azerbaijan [18,20,25].…”

“…The mutations were selected based on the previous studies performed on the Iranian subpopulations. Results of the previous studies along with the allele frequency of different a-thalassemia mutations in Iranian sub-populations are summarized in Table 1 [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Also, 340 individuals were excluded as no α-globin gene mutation has been detected in them (8.9%).…”

Prevalence and molecular characterization of alpha-thalassemia among newborns in Ardabil Province

“…Our results are similar to the study of East Azerbaijan province, in the north-west of Iran. (17). Data showed that -α 3.7 (6.1%) and -α4.2 (4.68%) are the most common mutation, causing α-thalassemia among 10,849 cases of α-thalassemia carriers in a comprehensive study of Iran (14).…”