Molecular spectrum and distribution of hemoglobinopathies in southwest of Iran: a seven-year retrospective study

Thalassemia is one of the most common inherited autosomal recessive disorders around the world. Over 200 mutations in the beta-globin gene and 70 mutations in the alpha-globin gene have been identified. This study aimed to assess a comprehensive prevalence of most frequent thalassemia mutations in Khuzestan Province, where is a belt of thalassemia in Iran. A total of 6946 subjects were enrolled for evaluating alpha-beta thalassemia from 2012 to 2018. In order to determine the silent mutations, subjects with microcytic hypochromic without anemia with normal Hb, HbA2, and HbF were included too. Genomic DNA was extracted, and ARMS-PCR, Gap-PCR, and DNA sequencing were used to detect thalassemia mutations. Of 6946 individuals, just 880 (12.6%) were normal, and 6066 (87.3%) were the carrier for thalassemia. The most frequent phenotype was alpha thalassemia (3984; 57.4%), followed by beta (1429; 20.6%), and alpha-beta thalassemia (653; 9.4%), respectively. The most frequent alpha mutation was − 3.7 (68.6%), followed by − α (6.2%), Codon 19 (2.9%), Poly A2 (2.7%), and − 5 nt (2.4%), respectively. In beta thalassemia, the more often mutations have been HbS (20.2%), IVSI-I (11.3%), Codon 36/37 (11.2%), and IVSI-110 (7.4%), respectively. Additional analysis showed that the most frequent genotypes in alpha and beta thalassemia were heterozygous carriers with − 3.7α (52.2%) and HbS (21.3%) mutations, respectively. The lowest Hb was found in heterozygote beta thalassemia carriers with IVSII-1β mutation (11.6 g/dl). Our findings showed that the distribution of beta thalassemia mutations differs from other previous data reported from Khuzestan and other provinces. This study is useful for screening and preventing thalassemia.