title: Prevalence of IVS1+1G>A mutation among Iranian Azeri Turkish patients with autosomal recessive non-syndromic hearing loss (ARNSHL).
abstract: OBJECTIVE
  Mutations in the GJB2 gene has been reported as a main cause for autosomal recessive non-syndromic hearing loss (ARNSHL) all over the world. IVS1+1G>A which is splice site mutation have been detected in several populations as disruptive mutation. This study has intended to assess the significance of this mutation, IVS1+1G>A, to the autosomal recessive non-syndromic genetic load among Iranian Azeri Turkish patients.
  
  
  METHODS
  Following our previous study, one hundred and seventy four unrelated patients with prelingual ARNSL were included in this study. Thirty nine patients had only one identified mutated allele, whereas hundred and thirty five patients were negative for coding region of GJB2. All these patients were screened for IVS1+1G>A by applying PCR-RFLP assay.
  
  
  RESULTS
  Among studied patients nine compound heterozygote with 35delG, delE120, 235delC were identified. Additionally, six patients were detected with only one IVS1+1G>A mutated allele. In these patients, the other mutated allele was left unidentified. One patient was identified to be homozygous for IVS1+1G>A. Further studies carried out on parents of positive cases, showed that one of the healthy parents (mother) to be homozygous for IVS1+1G>A mutation. By self-report, this person had no hearing impairment, although it is possible that she has mild or moderate hearing loss, which she is unable to detect. Her child was compound heterozygous (IVS1+1G>A/35delG) with profound deafness. The frequency of IVS1+1G>A was found to be about 4.9%, however the parental consanguinity was observed in 37.5% of IVS1+1G>A-mutated families.
  
  
  CONCLUSIONS
  Our results support founder effect regarding these mutations and the presence of an ancient ancestor is strengthened in comparison to hot spot hypothesis. Also the results suggest variable expressivity of IVS1+1G>A mutation with respect to hearing loss.
authors: Center of Excellence for Biodiversity, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran. jabbarpour@tabrizu.ac.ir
authors: Mortaza
authors: M
authors: Bonyadi
authors: Nikou
authors: N
authors: Fotouhi
authors: Mohsen
authors: M
authors: Esmaeili
mesh_terms: D000293:Adolescent; D000328:Adult; D043402:Cathepsin A / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins; D003241:Consanguinity; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency; D005808:Genes, Recessive; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D007223:Infant; D007492:Iran / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D022821:RNA Splice Sites / Q000235:genetics; D014421:Turkey / Q000208:ethnology
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D022821:RNA Splice Sites; D000072259:Connexin 26; C468629:CTSA protein, human; D043402:Cathepsin A