A comprehensive molecular characterization of beta thalassemia in a highly heterogeneous population

In Iran, the prevalence of beta-thalassemia trait is approximately 4–8% in most areas, and in Mazandaran province 10% of the population are carriers. Twenty four beta-globin gene mutations were identified in 1635 persons with beta-thalassemia trait using reverse dot blot and restriction fragment length polymorphism analysis. The predominant mutations included IVSII-1 (G-A) (61%), codon 30 (G-C) (7.5%), codon 22 (− 7 bp) (6.2%), codon 8 (− AA) (5.4%) and IVSI-5 (G-C) (3.6%). These mutations were in different haplotypes, with IVSII-1 being the most heterogeneous. Other less frequent mutations included IVS-II-745 (C-G), codon 44 (− C), codon 39 (C-T), codon 5 (− CT), IVS I-110 (G-A), IVSI-130 (G-C), Fr8/9 (+ G), IVSI-1 (G-A), and IVSI (− 25 bp). All rare mutations except IVSI-130 were encountered in a unique haplotype. The diversity of these mutations reflects the historical admixture of genes in the region. The high prevalence of IVSII-1 (G-A) compared to other parts of the country and the world suggests a founder effect. Our data provide a basis for genetic counseling and prenatal diagnosis.