title: GJB2 c.-23+1G>A mutation is second most common mutation among Iranian individuals with autosomal recessive hearing loss.
abstract: GJB2 mutation analysis is used routinely as a first step in genetic testing for autosomal recessive non-syndromic sensorineural hearing loss. Although most GJB2 mutations can be detected by sequencing of the exon 2 of this gene, a prevalent splice mutation, c.-23+1G>A (IVS1+1G>A), is not usually included in the analyzed region. In this study, we have developed an ARMS-PCR strategy for detection of this mutation among Iranian deaf individuals. A total of 418 Iranian individuals with hearing loss consistent with autosomal recessive non-syndromic sensorineural hearing loss based on audiological test result, medical history, physical examination and pedigree of the family, were included in this study. c.35delG and c.-23+1G>A mutations were detected by using ARMS-PCR. Direct sequencing of the exon 2 of the GJB2 gene was performed for mutation analysis of the coding region of this gene. Among 418 investigated cases, a total of 81 patients (~19.4 %) with biallelic pathogenic mutations in the GJB2 gene and 13 cases with only one pathogenic mutant allele were identified. The total allele frequencies of the two most frequent mutations, c.35delG and c.-23+1G>A, among mutated alleles were found to be around 59 and 15.7 %, respectively. High frequency of the c.35delG and c.-23+1G>A mutations among Iranian deaf individuals shows the importance of developing rapid and cost-effective methods for primary mutation screening methods before performing direct sequencing.
authors.affiliation: Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Pasteur St., Tehran, Iran, zeinalipasteur@yahoo.com.
authors.forename: Sirous
authors.initials: S
authors.lastname: Zeinali
authors.forename: Elham
authors.initials: E
authors.lastname: Davoudi-Dehaghani
authors.forename: Sarah
authors.initials: S
authors.lastname: Azadmehr
authors.forename: Samira
authors.initials: S
authors.lastname: DabbaghBagheri
authors.forename: Hamideh
authors.initials: H
authors.lastname: Bagherian
authors.forename: Mojdeh
authors.initials: M
authors.lastname: Jamali
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Zafarghandimotlagh
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Masoodifard
authors.forename: Ameneh
authors.initials: A
authors.lastname: BandehiSarhaddi
authors.forename: Leili
authors.initials: L
authors.lastname: Rejali
authors.forename: Sepideh
authors.initials: S
authors.lastname: Sahebi
mesh_terms: D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005787:Gene Frequency; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007492:Iran; D009154:Mutation
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26