Variations in Multiple Syndromic Deafness Genes Mimic Non-syndromic Hearing Loss

Sci Rep. 2016 Aug 26:6:31622. doi: 10.1038/srep31622.

Abstract

The genetics of both syndromic (SHL) and non-syndromic hearing loss (NSHL) is characterized by a high degree of genetic heterogeneity. We analyzed whole exome sequencing data of 102 unrelated probands with apparently NSHL without a causative variant in known NSHL genes. We detected five causative variants in different SHL genes (SOX10, MITF, PTPN11, CHD7, and KMT2D) in five (4.9%) probands. Clinical re-evaluation of these probands shows that some of them have subtle syndromic findings, while none of them meets clinical criteria for the diagnosis of the associated syndrome (Waardenburg (SOX10 and MITF), Kallmann (CHD7 and SOX10), Noonan/LEOPARD (PTPN11), CHARGE (CHD7), or Kabuki (KMT2D). This study demonstrates that individuals who are evaluated for NSHL can have pathogenic variants in SHL genes that are not usually considered for etiologic studies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cohort Studies
  • Connexins / genetics*
  • DNA Helicases / genetics
  • DNA-Binding Proteins / genetics
  • Deafness / genetics*
  • Exome
  • Female
  • Genetic Heterogeneity
  • Genetic Predisposition to Disease*
  • Genetic Variation
  • Humans
  • Male
  • Microphthalmia-Associated Transcription Factor / genetics
  • Mutation
  • Neoplasm Proteins / genetics
  • Pedigree
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics
  • SOXE Transcription Factors / genetics
  • Syndrome

Substances

  • Connexins
  • DNA-Binding Proteins
  • KMT2D protein, human
  • MITF protein, human
  • Microphthalmia-Associated Transcription Factor
  • Neoplasm Proteins
  • SOX10 protein, human
  • SOXE Transcription Factors
  • PTPN11 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • DNA Helicases
  • CHD7 protein, human

Supplementary concepts

  • Nonsyndromic Deafness