title: Identification of a SNP in a regulatory region of GJB2 associated with idiopathic nonsyndromic autosomal recessive hearing loss in a multicenter study.
abstract: OBJECTIVE
  Additional genetic changes in the regulatory region of the human GJB2 gene encoding the gap junction protein (Connexin 26) may contribute to sensorineural hearing loss.
  
  
  BACKGROUND
  Mutations in GJB2 cause up to 50% of autosomal recessive nonsyndromic hearing impairment (NSHI).
  
  
  METHODS
  In the present study, we screened the putative 5' GJB2 regulatory region for novel alterations.
  
  
  RESULTS
  In idiopathic familial cases of NSHI lacking known pathogenic alterations in GJB2, we identified a T→C transition (refSNP: rs117685390) in a putative transcription factor binding sequence 228 bp proximal to the transcriptional start site at a homozygous frequency of 0.125 (n = 40), significantly overrepresented in comparison to the homozygous allele frequencies of 0.043 in the normal-hearing Caucasian population (n = 211; p < 0.001). In a NSHI family, inheritance of the rs117685390 C allele segregated on independent chromosomes with NSHI in conjunction with heterozygous inheritance of c.35delG, the most common Caucasian mutation in the GJB2 coding region. In a patient group (n = 32) bearing heterozygous pathogenic c.35delG mutations, - rs117685390 C allele homozygosity was also highly overrepresented (0.25; p < 0.001) and not exclusively linked to the c.35delG mutation in cis in patients homozygous for c.35delG. However, in the majority of NSHI homozygous c.35delG chromosomes examined (91/94), c.35delG homozygosity was linked to the rs117685390 C allele in cis.
  
  
  CONCLUSIONS
  These results suggest that the rs117685390 C allele could represent a biomarker for the development of NSHI in Caucasian populations and may be included in risk assessment for the development of NSHI.
authors: Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria.
authors: Reinhard
authors: R
authors: Ramsebner
authors: Martin
authors: M
authors: Ludwig
authors: Trevor
authors: T
authors: Lucas
authors: Daniëlle
authors: D
authors: de Jong
authors: Gertrude
authors: G
authors: Hamader
authors: Ignacio
authors: I
authors: del Castillo
authors: Thomas
authors: T
authors: Parzefall
authors: Wolf-Dieter
authors: WD
authors: Baumgartner
authors: Christian
authors: C
authors: Schoefer
authors: Karoly
authors: K
authors: Szuhai
authors: Klemens
authors: K
authors: Frei
mesh_terms: D000328:Adult; D000483:Alleles; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26