LAUSR

Abstract α-Thalassemia (α-thal) is the most common monogenic disease that is caused by the absence or reduced expression of α-globin genes. The aim of this study was to investigate common α-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 α-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 –α3.7 (rightward deletion) (45.6%), polyadenylation site (αp°lyA2α) (α2) (AATAAA>AATGAA; HBA2: c.*92 A>G) (15.27%), – –MED (Mediterranean deletion) (6.86%), –α4.2 (leftward deletion), (6.17%), αCSα [Hb Constant Spring (Hb CS) (HBA2: c.427 T>C)] (4.62%), –α−5 nt (HBA2: c.95+2_95+6delTGAGG) (3.70%). All chromosomes bearing an α-globin point mutation [αp°lyA2α, –α−5 ntα, αCSα, αp°lyA1α (AATAAA> AATAAG; HBA2: c.*94 A>G)] showed only one haplotype that was present in most normal chromosomes, while the –α3.7 deletion was associated with three distinct haplotypes. Our results indicate that α-thal mutations are heterogeneous and –α3.7 and αp°lyA2α are the most prevalent mutations in this region. The presence of –α3.7 with three different haplotypes suggests an older history for this mutation. The high prevalence of αp°lyA2α 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).