title: GJB2 mutations in hearing impairment: identification of a broad clinical spectrum for improved genetic counseling.
abstract: OBJECTIVE
  Hearing impairment has a high prevalence affecting approximately 1 in 1000 newborn children. Alterations in the gap junction protein beta 2 (GJB2) and gap junction protein beta 6 (GJB6) are associated with nonsyndromic hearing impairment and should have a significant impact on genetic counseling.
  
  
  METHODS
  Various cases of nonsyndromic hearing impairment were screened for alterations in GJB2 and GJB6 in this clinical study.
  
  
  METHODS
  The prevalence of mutations in GJB2 encoding for connexin 26 in a patient group with nonsyndromic hearing impairment comprising 45 families and 57 sporadic cases was initially determined by sequencing. The role of GJB2 was then assessed in individuals with hearing impairment (3 families and 20 sporadic cases) who are usually excluded from analysis because of the presence of additional symptoms or in cases in which a role for nongenetic factors cannot be eliminated. In hearing-impaired individuals with heterozygous GJB2 mutations the recently identified 342-kb deletion truncating GJB6 called del(GJB6-D13S1830) as a digenetic component in hearing impairment was excluded by polymerase chain reaction.
  
  
  RESULTS
  Autosomal recessively inherited GJB2 mutations induced hearing impairment in 25.5% of individuals in the nonsyndromic hearing impairment group. GJB2 alterations were also seen in 17.4% of individuals in whom additional symptoms or a role for nongenetic involvement could not be excluded. In all, 15 different alterations in GJB2 were detected, including the previously unknown 154G>C, 557C>T, and 682C>T mutations, and these were correlated to clinical parameters.
  
  
  CONCLUSIONS
  Improved genetic counseling can be performed by screening for GJB2 alterations in patients with nonsyndromic hearing impairment including patients within groups for which a role for exogenetic factors cannot be excluded. Specific genetic counseling for GJB2-linked hearing impairment in heterozygotes will depend on future research.
authors.affiliation: Department of Otorhinolaryngology, Medical University of Vienna, Austria. klemens.frei@akh-wein.ac.at
authors.forename: Klemens
authors.initials: K
authors.lastname: Frei
authors.forename: Reinhard
authors.initials: R
authors.lastname: Ramsebner
authors.forename: Trevor
authors.initials: T
authors.lastname: Lucas
authors.forename: Gertrude
authors.initials: G
authors.lastname: Hamader
authors.forename: Károly
authors.initials: K
authors.lastname: Szuhai
authors.forename: Klara
authors.initials: K
authors.lastname: Weipoltshammer
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Baumgartner
authors.forename: Franz J
authors.initials: FJ
authors.lastname: Wachtler
authors.forename: Karin
authors.initials: K
authors.lastname: Kirschhofer
mesh_terms: D002872:Chromosome Deletion; D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics*; D005808:Genes, Recessive; D005817:Genetic Counseling; D034381:Hearing Loss / Q000151:congenital / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D015995:Prevalence; D017422:Sequence Analysis, DNA
chemical_list: D000075302:Connexin 30; D017630:Connexins; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; D000072259:Connexin 26