GJB2 mutations and genotype-phenotype correlation in 335 patients from germany with nonsyndromic sensorineural hearing loss: evidence for additional recessive mutations not detected by current methods

Audiol Neurootol. 2010;15(6):375-82. doi: 10.1159/000297216. Epub 2010 Mar 17.

Abstract

We report on 335 patients (319 families) with mild-to-profound nonsyndromic sensorineural hearing loss. We identified 178 mutated GJB2 alleles representing 29 different sequence changes (including 3 novel mutations: Q7P, N14D, H100Q), and 2 alleles with the deletion del(GJB6-D13S1830) of the GJB6 gene. Eleven GJB2 mutations (119 mutated alleles) were truncating (T), and 18 mutations (59 alleles) were nontruncating (NT). Biallelic GJB2 mutations were found in 71 patients (21.2%; 67 families; 25 different genotypes). Audiograms of 62 patients (56 families) with biallelic GJB2 mutations typically indicated a profound hearing loss with T/T mutations, moderate hearing loss with T/NT mutations, and mild hearing impairment with NT/NT mutations (p < 0.01, Student's t test). From 37 patients (34 families) with biallelic GJB2 mutations, audiograms at different ages were available and indicated progressive hearing loss (>15 dB) in 10 patients (27.0%, 10 families). Interestingly, we identified an unexpectedly large subset of patients (n = 29; 8.7%) presenting with only one GJB2 mutation (n = 14 T/wild-type; n = 15 NT/wild-type). This strongly suggests the presence of additional recessive mutations that are not detected by current GJB2 mutation and GJB6 deletion analyses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Audiometry
  • Connexin 26
  • Connexins / genetics*
  • Female
  • Gene Frequency
  • Genes, Recessive
  • Genetic Association Studies
  • Genotype
  • Germany
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Male
  • Mutation
  • Phenotype
  • Polymerase Chain Reaction

Substances

  • Connexins
  • GJB2 protein, human
  • Connexin 26