title: Detailed hearing and vestibular profiles in the patients with COCH mutations.
abstract: OBJECTIVE
  To evaluate the clinical features of Japanese DFNA9 families with mutations of the COCH gene.
  
  
  METHODS
  Mutation screening was performed using targeted next-generation sequencing (NGS) for 63 previously reported deafness genes. The progression of hearing loss and vestibular dysfunction were evaluated by pure-tone audiometry, caloric testing, cVEMP, and computed dynamic posturography.
  
  
  RESULTS
  We detected 1 reported mutation of p.G88E and 2 novel mutations of p.I372T and p.C542R. The patients with the novel mutations of p.I372T and p.C542R within the vWFA2 domain showed early onset progressive hearing loss, and the patients with the p.G88E mutation showed late onset hearing loss and acute hearing deterioration over a short period. Vestibular symptoms were reported in the patients with p.G88E and p.C542R. Vestibular testing was performed for the family with the p.G88E mutation. Severe vestibular dysfunction was observed in the proband, and the proband's son showed unilateral semicircular canal dysfunction with mild hearing loss.
  
  
  CONCLUSIONS
  Targeted exon resequencing of selected genes using NGS successfully identified mutations in the relatively rare deafness gene, COCH, in the Japanese population. The phenotype is compatible with that described in previous reports. Additional supporting evidence concerning progressive hearing loss and deterioration of vestibular function was obtained from our study.
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Tsukada
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Ichinose
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Miyagawa
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Mori
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hattori
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Shin-Ya
authors.initials: SY
authors.lastname: Nishio
authors.affiliation: Department of Otorhinolaryngology, Kobe City Medical Center General Hospital, Hyogo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Kitajiri
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto, Japan usami@shinshu-u.ac.jp.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Usami
mesh_terms: D000368:Aged; D001301:Audiometry, Pure-Tone; D002150:Caloric Tests; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics*; D004576:Electromyography; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D015837:Vestibular Diseases / Q000175:diagnosis / Q000235:genetics
chemical_list: C110668:COCH protein, human; D016326:Extracellular Matrix Proteins
keywords: COCH; DFNA9; Massively Parallel Sequencing; next-generation sequencing; progressive hearing loss; vestibular dysfunction