A Comprehensive Molecular Investigation of α-Thalassemia in an Iranian Cohort from Different Provinces of North Iran

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 –α^3.7 (rightward deletion) (45.6%), polyadenylation site (α^p°^lyA2α) (α2) (AATAAA>AATGAA; HBA2: c.*92 A>G) (15.27%), – –^MED (Mediterranean deletion) (6.86%), –α^4.2 (leftward deletion), (6.17%), α^CSα [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 [α^p°^lyA2α, –α^−5 ntα, α^CSα, α^p°^lyA1α (AATAAA> AATAAG; HBA2: c.*94 A>G)] showed only one haplotype that was present in most normal chromosomes, while the –α^3.7 deletion was associated with three distinct haplotypes. Our results indicate that α-thal mutations are heterogeneous and –α^3.7 and α^p°^lyA2α are the most prevalent mutations in this region. The presence of –α^3.7 with three different haplotypes suggests an older history for this mutation. The high prevalence of α^p°^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).

Keywords:

• α-Thalassemia (α-thal)
• haplotype
• Iran
• mutations

Acknowledgements

The authors would like to acknowledge Dr. Iswari Setianingsih from the Eijkman Institute for Molecular Biology, Jakarta, Indonesia, for providing the α-thal control genomes.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This study was partly supported by the Research Deputy Council of Babol University of Medical Sciences, Babol, Iran.