Combined genetic approaches yield a 48% diagnostic rate in a large cohort of French hearing-impaired patients

Sci Rep. 2017 Dec 1;7(1):16783. doi: 10.1038/s41598-017-16846-9.


Hearing loss is the most common sensory disorder and because of its high genetic heterogeneity, implementation of Massively Parallel Sequencing (MPS) in diagnostic laboratories is greatly improving the possibilities of offering optimal care to patients. We present the results of a two-year period of molecular diagnosis that included 207 French families referred for non-syndromic hearing loss. Our multi-step strategy involved (i) DFNB1 locus analysis, (ii) MPS of 74 genes, and (iii) additional approaches including Copy Number Variations, in silico analyses, minigene studies coupled when appropriate with complete gene sequencing, and a specific assay for STRC. This comprehensive screening yielded an overall diagnostic rate of 48%, equally distributed between DFNB1 (24%) and the other genes (24%). Pathogenic genotypes were identified in 19 different genes, with a high prevalence of GJB2, STRC, MYO15A, OTOF, TMC1, MYO7A and USH2A. Involvement of an Usher gene was reported in 16% of the genotyped cohort. Four de novo variants were identified. This study highlights the need to develop several molecular approaches for efficient molecular diagnosis of hearing loss, as this is crucial for genetic counselling, audiological rehabilitation and the detection of syndromic forms.

MeSH terms

  • Cohort Studies
  • Computer Simulation
  • Connexin 26
  • Connexins / genetics*
  • DNA Copy Number Variations*
  • Early Diagnosis
  • France
  • Genetic Predisposition to Disease
  • Genetic Testing / methods
  • Hearing Loss / diagnosis*
  • Hearing Loss / genetics
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Male
  • Mutation
  • Sensitivity and Specificity
  • Sequence Analysis, DNA / methods
  • White People / genetics*


  • Connexins
  • GJB2 protein, human
  • Connexin 26