A Comprehensive Molecular Investigation of α-Thalassemia in an Iranian Cohort from Different Provinces of North Iran (original) (raw)
a-Thalassemia (a-thal) is the most common monogenic disease that is caused by the absence or reduced expression of a-globin genes. The aim of this study was to investigate common a-globin mutations and their associated haplotypes in four northern provinces of Iran (Gilan, Mazandaran, Golestan, Khorasan). One thousand, one hundred and ninety-one persons were tested for a-thal mutations by gap-polymerase chain reaction (PCR), reverse dot-blot hybridization, restriction fragment length polymorphism (RFLP) analysis and sequencing. Of the nine different mutations found, the most frequent were-a 3.7 (rightward deletion) (45.6%), polyadenylation site (a plyA2 a) (a2) (AATAAA>AATGAA; HBA2: c. Ã 92 A>G) (15.27%),-MED (Mediterranean deletion) (6.86%),-a 4.2 (leftward deletion), (6.17%), a CS a [Hb Constant Spring (Hb CS) (HBA2: c.427 T>C)] (4.62%),-a À5 nt (HBA2: c.95þ2_95þ6delTGAGG) (3.70%). All chromosomes bearing an a-globin point mutation [a plyA2 a,-a À5 nt a, a CS a, a plyA1 a (AATAAA> AATAAG; HBA2: c. Ã 94 A>G)] showed only one haplotype that was present in most normal chromosomes, while the-a 3.7 deletion was associated with three distinct haplotypes. Our results indicate that a-thal mutations are heterogeneous and-a 3.7 and a plyA2 a are the most prevalent mutations in this region. The presence of-a 3.7 with three different haplotypes suggests an older history for this mutation. The high prevalence of a plyA2 a in Mazandaran Province, Iran compared to other parts of the country and the world, suggests a founder effect. Altogether, we here provide further data confirming the heterogeneity of the northern population of Iran. These data may contribute to the establishment of a national mutation database, more accurate genetic counseling and prenatal diagnosis (PND).