title: Finding mutation within non-coding region of GJB2 reveals its importance in genetic testing of hearing loss in Iranian population.
abstract: OBJECTIVE
  Hereditary hearing loss is the most common neurosensory disorder in humans. Half of the cases have genetic etiology with extraordinary genetic heterogeneity. Mutations in one gene, GJB2, are the most common cause for autosomal recessive non-syndromic hearing loss (ARNSHL) in many different populations. GJB2 encodes a gap junction channel protein (connexin 26), and is located on DFNB1 locus on chromosome 13q12.11 which also involve another connexin gene, GJB6. Mutation screening of GJB2 revealed that a high number of patients with deaf phenotype have heterozygous genotype and carry only one mutant allele. As the first comprehensive study in Iran, we have targeted GJB2-related Iranian heterozygotes, looking for second mutant allele which leads to hearing impairment. They bear first mutation in their coding exon of GJB2.
  
  
  METHODS
  Using PCR-based direct sequencing, we assessed 103 patients with ARNSHL for variants in non-coding exon and promoter region of this gene, for the first time in Iran.
  
  
  RESULTS
  We have identified the second mutant allele in splice site of exon-1 of GJB2 which is known as IVS1+1G>A in 17 probands. We found no mutation in promoter region of GJB2.
  
  
  CONCLUSIONS
  Our findings reveal that IVS1+1G>A mutation in noncoding exon of GJB2 is the most common mutation after 35delG within multi ethnical Iranian heterozygote samples. It emphasizes to approach exon1 of GJB2 in case of ARNSHL genetic diagnosis.
authors.affiliation: Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran; Deputy of Student Research, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Atie
authors.initials: A
authors.lastname: Kashef
authors.affiliation: Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Nooshin
authors.initials: N
authors.lastname: Nikzat
authors.affiliation: Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Niloofar
authors.initials: N
authors.lastname: Bazzazadegan
authors.affiliation: Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Fattahi
authors.affiliation: Department of Genetic, Kerman Welfare Organization, Kerman, Iran.
authors.forename: Farahnaz
authors.initials: F
authors.lastname: Sabbagh-Kermani
authors.affiliation: Genetic Counseling Center, Shiraz Welfare Organization, Fars, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Taghdiri
authors.affiliation: Welfare Counseling Center, Isfahan, Iran.
authors.forename: Batool
authors.initials: B
authors.lastname: Azadeh
authors.affiliation: Mashhad Genetic Counseling Center, Mashhad, Khorasan, Iran.
authors.forename: Faezeh
authors.initials: F
authors.lastname: Mojahedi
authors.affiliation: Welfare Counseling Center, Mazandaran, Iran.
authors.forename: Atefeh
authors.initials: A
authors.lastname: Khoshaeen
authors.affiliation: Genetic Counseling Center, Family Health Clinic, Mobasher Hospital, Hamedan, Iran.
authors.forename: Haleh
authors.initials: H
authors.lastname: Habibi
authors.affiliation: Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Najmabadi
authors.affiliation: Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. Electronic address: kahrizi@yahoo.com.
authors.forename: Kimia
authors.initials: K
authors.lastname: Kahrizi
mesh_terms: D000483:Alleles; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007492:Iran / Q000453:epidemiology; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26
keywords: Autosomal recessive non-syndromic hearing loss; GJB2; Heterozygote; IVS1+1G>A; Noncoding mutation