title: GJB2-associated hearing loss: systematic review of worldwide prevalence, genotype, and auditory phenotype.
abstract: OBJECTIVE
  To perform a systematic review of GJB2-associated hearing loss to describe genotype distributions and auditory phenotype.
  
  
  METHODS
  230 primary studies identified from Pubmed.
  
  
  METHODS
  Pubmed was searched systematically to screen broadly for any study reporting on genotype and carrier frequencies for biallelic GJB2-associated hearing loss in defined populations around the world. Genotype and audiometric data were extracted and subjected to meta-analysis to determine genotype distributions, carrier frequencies, rates of asymmetric or progressive hearing loss, and imaging abnormalities.
  
  
  RESULTS
  A total of 216 articles comprising over 43,000 hearing-loss probands were included. The prevalence of biallelic GJB2-associated hearing loss was consistent across most of the 63 countries examined, with different mutations being predominant in different countries. Common mutations were found in greater than 3% of the general population worldwide. Meta-analysis of 48 case-control studies demonstrated a two-fold higher carrier frequency among hearing-impaired individuals compared to normal-hearing controls for truncating alleles, but not V37I. Progression, asymmetry, and imaging abnormalities were present in 14% to 19% of individuals with GJB2-associated hearing loss.
  
  
  CONCLUSIONS
  GJB2 mutations are highly prevalent around the world. The multiple predominant mutations present in different populations attest to the importance of this gene for normal cochlear function and suggests an evolutionary heterozygote advantage. The unusually high carrier rate for truncating mutations among hearing-impaired individuals is consistent with either the presence of complementary mutations or a carrier phenotype. The significant rate of asymmetry and progression highlights the importance of diagnostic workup and close follow-up for this highly variable condition.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, U.S.A.
authors.forename: Dylan K
authors.initials: DK
authors.lastname: Chan
authors.forename: Kay W
authors.initials: KW
authors.lastname: Chang
mesh_terms: D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005838:Genotype; D014943:Global Health; D034381:Hearing Loss / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010641:Phenotype; D015995:Prevalence
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26
keywords: Hearing loss; connexin 26; genetics