A Comprehensive Molecular Investigation of α-Thalassemia in an Iranian Cohort from Different Provinces of North Iran. (2nd January 2017)

• Record Type: Journal Article
• Authors: Eftekhari, Hajar; Tamaddoni, Ahmad; Mahmoudi Nesheli, Hassan; Vakili, Mohsen; Sedaghat, Sadegh; Banihashemi, Ali; Azizi, Mandana; Youssefi Kamangar, Reza; Akhavan-Niaki, Haleh
• Is Part Of: Hemoglobin. Volume 41:Number 1(2017)
• Page Start: 32
• Page End: 37
• Publication Date: 2017-01-02
• Subjects: α-Thalassemia (α-thal) -- haplotype -- Iran -- mutations; Hemoglobinopathy -- Periodicals; Hemoglobin -- Periodicals; Hematology -- Periodicals; Thalassemia -- Periodicals; Blood -- Diseases -- Periodicals; 612.1111
• DOI: 10.1080/03630269.2017.1299753
• Languages: English
• ISSNs: 0363-0269

Abstract

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 ° lyA2 α) (α2) (AAT A AA>AAT G AA; HBA2 : c.*92 A>G) (15.27%), – – MED (Mediterranean deletion) (6.86%), –α 4.2 (leftward deletion), (6.17%), α CS α [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 ° lyA2 α, –α −5 nt α, α CS α, α p ° lyA1 α (AATAA A > AATAA G ; 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 ° lyA2 α 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 ° lyA2 α 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).