Comprehensive Analysis of Deafness Genes in Families with Autosomal Recessive Nonsyndromic Hearing Loss

PLoS One. 2015 Nov 11;10(11):e0142154. doi: 10.1371/journal.pone.0142154. eCollection 2015.


Comprehensive genetic testing has the potential to become the standard of care for individuals with hearing loss. In this study, we investigated the genetic etiology of autosomal recessive nonsyndromic hearing loss (ARNSHL) in a Turkish cohort including individuals with cochlear implant, who had a pedigree suggestive of an autosomal recessive inheritance. A workflow including prescreening of GJB2 and a targeted next generation sequencing panel (Illumına TruSightTM Exome) covering 2761 genes that we briefly called as mendelian exome sequencing was used. This panel includes 102 deafness genes and a number of genes causing Mendelian disorders. Using this approach, we identified causative variants in 21 of 29 families. Three different GJB2 variants were present in seven families. Remaining 14 families had 15 different variants in other known NSHL genes (MYO7A, MYO15A, MARVELD2, TMIE, DFNB31, LOXHD1, GPSM2, TMC1, USH1G, CDH23). Of these variants, eight are novel. Mutation detection rate of our workflow is 72.4%, confirming the usefulness of targeted sequencing approach in NSHL.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Connexin 26
  • Connexins / genetics
  • Deafness / diagnosis
  • Deafness / genetics*
  • Exome / genetics
  • Family Health
  • Female
  • Gene Frequency
  • Genes, Recessive*
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Humans
  • Male
  • Mutation
  • Pedigree
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sequence Analysis, DNA / methods


  • Connexins
  • GJB2 protein, human
  • Connexin 26

Supplementary concepts

  • Nonsyndromic Deafness