A dominant mutation in the stereocilia-expressing gene TBC1D24 is a probable cause for nonsyndromic hearing impairment

Hum Mutat. 2014 Jul;35(7):814-8. doi: 10.1002/humu.22558. Epub 2014 May 6.


Mutations in TBC1D24 have been linked to a variety of epileptic syndromes and recently to syndromic hearing impairment DOORS syndrome and nonsyndromic hearing impairment DFNB86. All TBC1D24 mutations reported so far were inherited in the recessive mode. In a dominant family segregated with late-onset, progressive, nonsyndromic hearing impairment, linkage analysis revealed a 2.07 Mb candidate region on chromosome 16p13.3 that contains TBC1D24. Whole-exome sequencing identified a heterozygous p.Ser178Leu variant of TBC1D24 as the only candidate mutation segregating with the hearing loss within the family. In perinatal mouse cochlea, we detected a restricted expression of Tbc1d24 in the stereocilia of the hair cells as well as in the spiral ganglion neurons. Our study suggested that the p.Ser178Leu mutation of TBC1D24 is a probable cause for dominant, nonsyndromic hearing impairment. Identification of TBC1D24 as the stereocilia-expressing gene may shed new light on its specific function in the inner ear.

Keywords: TBC1D24; autosomal dominant; hearing impairment; hearing loss; nonsyndromic; stereocilia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Child
  • DNA Mutational Analysis
  • Deafness / diagnosis
  • Deafness / genetics
  • Exome
  • Female
  • GTPase-Activating Proteins
  • Gene Expression
  • Genes, Dominant*
  • Genetic Linkage
  • Humans
  • Male
  • Membrane Proteins
  • Mice
  • Molecular Sequence Data
  • Mutation*
  • Nerve Tissue Proteins
  • Pedigree
  • Sequence Alignment
  • Stereocilia / genetics*
  • Young Adult


  • Carrier Proteins
  • GTPase-Activating Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • TBC1D24 protein, human

Supplementary concepts

  • Nonsyndromic Deafness