title: Prevalence and audiological profiles of GJB2 mutations in a large collective of hearing impaired patients.
abstract: Mutations in the GJB2 gene are known to represent the commonest cause of hereditary and congenital hearing loss. In this study, a complete sequencing of the GJB2 gene in a cohort of 506 patients from a single, large cochlear implant program in Europe was performed. Audiological testing for those patients who could actively participate was performed using pure tone audiometry (PTA). Those unable to undergo PTA were measured using click-auditory brainstem response (ABR). Data analysis was performed to determine genotype-phenotype correlations of the mutational status vs. audiological profiles and vs. age at the time of presentation. An overall prevalence of biallelic mutations of 13.4% was found for the total collective. When subsets of younger patients were examined, the prevalence increased to 27% of those up to age 18 and 35% of those up to age 5 at the time of testing, respectively. This increase was found to be highly significant (p < 0.001). Analysis of the mean PTA thresholds revealed a strong correlation between allele combination status and mean PTA (p = 0.021). The prevalence of simple heterozygotes was found to be approximately 10.1%, which is around 3.3 times the value expected in the general population. As GJB2 follows a recessive pattern of inheritance, the question arises as to why such a large fraction of simple heterozygotes was observed among the hearing impaired patients included in this study.
authors.affiliation: Department of Otolaryngology, Hannover Medical School, Hannover, Germany; Cluster of Excellence, Hearing4All, Germany. Electronic address: burke.william@mh-hannover.de.
authors.forename: W F
authors.initials: WF
authors.lastname: Burke
authors.affiliation: Department of Otolaryngology, Hannover Medical School, Hannover, Germany; Cluster of Excellence, Hearing4All, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Warnecke
authors.affiliation: Institute for Human Genetics, Hannover Medical School, Hannover, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schöner-Heinisch
authors.affiliation: Department of Otolaryngology, Hannover Medical School, Hannover, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Lesinski-Schiedat
authors.affiliation: Department of Otolaryngology, Hannover Medical School, Hannover, Germany; Cluster of Excellence, Hearing4All, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Maier
authors.affiliation: Department of Otolaryngology, Hannover Medical School, Hannover, Germany; Cluster of Excellence, Hearing4All, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Lenarz
mesh_terms: D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001301:Audiometry, Pure-Tone; D001309:Auditory Threshold; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005858:Germany / Q000453:epidemiology; D006309:Hearing / Q000235:genetics*; D006311:Hearing Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D055815:Young Adult
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26
keywords: Connexin 26; GJB2; Gap junctions; Genetics; Hearing loss; Non-syndromic