Whole exome sequencing identifies new causative mutations in Tunisian families with non-syndromic deafness

PLoS One. 2014 Jun 13;9(6):e99797. doi: 10.1371/journal.pone.0099797. eCollection 2014.

Abstract

Identification of the causative mutations in patients affected by autosomal recessive non syndromic deafness (DFNB forms), is demanding due to genetic heterogeneity. After the exclusion of GJB2 mutations and other mutations previously reported in Tunisian deaf patients, we performed whole exome sequencing in patients affected with severe to profound deafness, from four unrelated consanguineous Tunisian families. Four biallelic non previously reported mutations were identified in three different genes: a nonsense mutation, c.208C>T (p.R70X), in LRTOMT, a missense mutation, c.5417T>C (p.L1806P), in MYO15A and two splice site mutations, c.7395+3G>A, and c.2260+2T>A, in MYO15A and TMC1 respectively. We thereby provide evidence that whole exome sequencing is a powerful, cost-effective screening tool to identify mutations causing recessive deafness in consanguineous families.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Connexin 26
  • Connexins / genetics
  • Deafness / genetics*
  • Exome / genetics
  • Female
  • Hearing Loss, Sensorineural / genetics
  • Humans
  • Male
  • Mutation / genetics
  • Pedigree

Substances

  • Connexins
  • GJB2 protein, human
  • Connexin 26

Supplementary concepts

  • Deafness, Autosomal Recessive

Grants and funding

This work was supported by the Tunisian Ministry of Public Health, the Ministry of Higher Education and Scientific Research (LR11IPT05) and by the E.C. Grant agreement N° 295097 for FP7 project GM-NCD-Inco and BNP Paribas foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.