title: 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 -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 -α3.7deletion was associated with three distinct haplotypes. Our results indicate that α-thal mutations are heterogeneous and -α3.7and αp°lyA2α are the most prevalent mutations in this region. The presence of -α3.7with 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).
authors.affiliation: a Department of Genetics, Cellular and Molecular Biology Research Centre , Babol University of Medical Sciences , Babol , Iran.|b Department of Genetics, Faculty of Medicine , Babol University of Medical Sciences , Babol , Iran.
authors.forename: Hajar
authors.initials: H
authors.lastname: Eftekhari
authors.affiliation: c Department of Hematology, Non-Communicable Pediatric Diseases Research Centre , Babol University of Medical Sciences , Babol , Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Tamaddoni
authors.affiliation: c Department of Hematology, Non-Communicable Pediatric Diseases Research Centre , Babol University of Medical Sciences , Babol , Iran.
authors.forename: Hassan
authors.initials: H
authors.lastname: Mahmoudi Nesheli
authors.affiliation: d Department of Internal Medicine, Ayatollah Roohani Hospital, Babol University of Medical Sciences , Babol , Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Vakili
authors.affiliation: d Department of Internal Medicine, Ayatollah Roohani Hospital, Babol University of Medical Sciences , Babol , Iran.
authors.forename: Sadegh
authors.initials: S
authors.lastname: Sedaghat
authors.affiliation: e Genetic Laboratory of Amirkola Children Hospital, Babol University of Medical Sciences , Babol , Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Banihashemi
authors.affiliation: e Genetic Laboratory of Amirkola Children Hospital, Babol University of Medical Sciences , Babol , Iran.
authors.forename: Mandana
authors.initials: M
authors.lastname: Azizi
authors.affiliation: e Genetic Laboratory of Amirkola Children Hospital, Babol University of Medical Sciences , Babol , Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Youssefi Kamangar
authors.affiliation: a Department of Genetics, Cellular and Molecular Biology Research Centre , Babol University of Medical Sciences , Babol , Iran.|b Department of Genetics, Faculty of Medicine , Babol University of Medical Sciences , Babol , Iran.|e Genetic Laboratory of Amirkola Children Hospital, Babol University of Medical Sciences , Babol , Iran.
authors.forename: Haleh
authors.initials: H
authors.lastname: Akhavan-Niaki
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D009154:Mutation; D016017:Odds Ratio; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D055542:alpha-Globins
keywords: Iran; haplotype; mutations; α-Thalassemia (α-thal)