Mutations in the COCH gene are a frequent cause of autosomal dominant progressive cochleo-vestibular dysfunction, but not of Meniere's disease

Shin Ichi Usami, Kentaro Takahashi, Isamu Yuge, Akihiro Ohtsuka, Atsushi Namba, Satoko Abe, Erik Fransen, Laszlo Patthy, Gottfried Otting, Guy Van Camp

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The COCH gene is the only gene identified in man that causes autosomal dominantly inherited hearing loss associated with vestibular dysfunction. The condition is rare and only five mutations have been reported worldwide. All affected families showed a similar progressive hearing loss and vestibular dysfunction. Since Meniere's disease-like symptoms have also been described in some families, it was suggested that COCH mutations might be present in some patients diagnosed with Meniere's disease. In this study, using a Japanese population, we performed a COCH mutation analysis in 23 patients from independent families with autosomal dominant hearing impairment, four of whom reported vestibular symptoms, and also in 20 Meniere's patients. While a new point mutation, A119T, was found in a patient with autosomal dominant hearing loss and vestibular symptoms, no mutations were found in the Meniere's patients. Like all other previously identified COCH mutations, the mutation identified here is a missense mutation located in the FCH domain of the protein. The current mutation is located in close spatial proximity to W117, in which a mutation (W117R) had previously been associated with autosomal dominant hearing loss. Model building suggests that, like the W117R mutation, the A119T mutation does not affect the structural integrity of the FCH domain, but may interfere with the interaction with a yet unknown binding partner. We conclude that mutations in the COCH gene are responsible for a significant fraction of patients with autosomal dominantly inherited hearing loss accompanied by vestibular symptoms, but not for dominant hearing loss without vestibular dysfunction, or sporadic Meniere's disease.

Original languageEnglish
Pages (from-to)744-748
Number of pages5
JournalEuropean Journal of Human Genetics
Issue number10
Publication statusPublished - Oct 1 2003



  • COCH
  • Deafness
  • FCH domain
  • Meniere's disease
  • Vertigo

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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