A systematic review of hearing and vestibular function in carriers of the Pro51Ser mutation in the COCH gene

Eur Arch Otorhinolaryngol. 2019 May;276(5):1251-1262. doi: 10.1007/s00405-019-05322-x. Epub 2019 Feb 26.


Background and objectives: The Pro51Ser (P51S) COCH mutation is characterized by a late-onset bilateral sensorineural hearing loss (SNHL) and progressive vestibular deterioration. The aim of this study was to carry out a systematic review of all reported hearing and vestibular function data in P51S COCH mutation carriers and its correlation with age.

Materials and methods: Scientific databases including Medline, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, ISI Web of Knowledge, and Web of Science were searched to accumulate information about hearing outcome and vestibular function. Eleven genotype-phenotype correlation studies of the P51S COCH variant were identified and analyzed.

Results: The SNHL starts at the age of 32.8 years. The Annual Threshold Deterioration is 3 decibel hearing loss (dB HL) per year (1-24 dB HL/year). Profound SNHL was observed at 76 years on average (60-84 years). 136 individual vestibular measurements were collected from 86 carriers. The onset of the vestibular dysfunction was estimated around 34 years (34-40 years), and vestibular deterioration rates were higher than those of the SNHL, with complete bilateral loss observed between 49 and 60 years.

Conclusion: Both audiometric and vestibular data were processed with much different methodologies and pre-symptomatic P51S carriers were systematically underrepresented. Further delineation of this correlation would benefit cross-sectional and longitudinal study involving all (pre-symptomatic and symptomatic) P51S carriers.

Keywords: COCH mutation; DFNA9; Hearing; Vestibular function.

Publication types

  • Systematic Review

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Audiometry
  • Extracellular Matrix Proteins / genetics*
  • Female
  • Hearing / genetics
  • Hearing Loss, Sensorineural / genetics*
  • Hearing Loss, Sensorineural / physiopathology
  • Heterozygote*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Vestibule, Labyrinth / physiopathology*


  • COCH protein, human
  • Extracellular Matrix Proteins