a large cohort study of genotype and phenotype correlations of beta-thalassemia in iranian population

background: thalassemia syndromes are the most prevalent single gene disorders in iran. this study aimed to evaluate the effect of different types of beta-globin gene mutations, co-inheritance of alpha-globin gene mutations and/or xmn1 snp on disease phenotype in a large cohort of iranian patients. subjects and methods: in total, 433 patients were clinically classified into β-thalassemia major (tm) or intermedia (ti). multiplex pcr, arms-pcr, rflp-pcr and dna sequencing were performed to identify both α- and β-globin gene mutations and xmn1 polymorphism as well. all data were compared and analyzed by spss software in tm and ti groups consequently. results: a total of 39 different β-globin mutations were identified. among them, the most common were ivs iint1 (40.33%) followed by ivs int5 (9.56%), c30 (7.22%) and fr8-9(7%). all patients were subjected to evaluate common α-globin gene deletions. the patients inherited concomitant mutations of α- and β-globin, showed no clinical modifications compared with those who had only β-globin mutation. the ti patients showed a significant increase in frequency of both heterozygous and homozygous form of the xmn1 polymorphism. it was also found that β 0 /β 0 genotype patients, inherited the xmn1 polymorphism required lesser blood transfusion. conclusion: no significant differences were observed, on the severity of disease, between patient's inherited defective α- and β-globin genes and ones with just β-globin gene mutation. taking the results of this research into account, xmn1 polymorphism can be considered as an important genetic factor modulating the severity of disease.