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Background Thalassemia is common in the Iranian population, and it must be considered in the differential diagnosis of the microcytic hypochromic anemia. The molecular analysis of β-thalassemia is necessary for prenatal molecular diagnosis. A-thalassemia caused by loss of function of either one of the two duplicated α-globin genes or in less frequent non deletion mutations mostly located in the α2-globin gene. Materials and Methods DNA were extracted from 100 whole blood using salting out method. The PCR was performed in two segments for entire β-globin gene and the α1 and α2-globin genes separately. Direct sequencing was carried out. The Gap-PCR was performed using published primers. Results Clinical application of DNA analysis on thalassemic patients showed 42 persons have various β-thalassemia mutations, 48 persons with αα/-α3.7 deletion and 8 persons with non deletion mutations of α1 and α2-globin genes. These mutations determined by direct sequencing of entire β-globin, α1 and α2-globin genes and Gap-PCR for detection of deletions. Thirteen different β-thalassemia alleles were identified, the most common being IVS I-5(G>C) and CAP+1 (A>C). The most α -globin mutation being αα/-α3.7 deletion. Conclusions The frequency of mutations in North-east of Iran shows that these mutations are not the same as frequent mutation in other province of Iran. Feature study could determine molecular analysis of frequent mutations, which is useful for differentiating mild from severe alleles. In addition, mutation definition in carriers should be necessary for prenatal testing and genetic counseling. [ABSTRACT FROM AUTHOR]

The major defect in α-thalassemia (α-thal) is a single or double gene deletion. The aim of this study was to evaluate the α-thal mutations in two provinces of Southern Iran, Fars & Kohkeloye and Bouyer Ahmad. A total of 2000 subjects with microcytic hypochromic anemia was selected as a study group; finally, 1177 subjects were found to be α-thal mutation carriers by gap-polymerase chain reaction (gap-PCR) protocols and were confirmed by multiplex PCR and reverse hybridization test strips. A total of 1195 mutated α-globin alleles was identified in these patients that includes at least 10 different gene mutations. The most common mutation found was -α3.7 (rightward deletion) (71.7%%) and α−5 nt (IVS-I, -TGAGG) and the polyadenylation signal site (poly A1; AATAA A>AATAA G) were the second and third most common mutations (7.0 and 4.2%%, respectively). In countries like Iran, with a high prevalence of thalassemia, identifying different mutations is helpful in carrier screening, genetic counseling and prenatal diagnosis of at-risk couples for the prevention of the birth of babies affected by severe thalassemic anomalies. [ABSTRACT FROM AUTHOR]

Abstract: 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 (−7bp) (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 (−25bp). 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. [Copyright &y& Elsevier]