title: Variable clinical features in patients with CDH23 mutations (USH1D-DFNB12).
abstract: OBJECTIVE
  To describe the findings of audiovestibular and ophthalmologic examinations in four families with mutations in the CDH23 gene.
  
  
  METHODS
  Family study.
  
  
  METHODS
  Tertiary referral center.
  
  
  METHODS
  Four DFNB12 patients from a large consanguineous Dutch family and six patients from three different Usher syndrome Type ID families were examined. All were identified by at least one pathogenic mutation in the CDH23 gene.
  
  
  METHODS
  Audiovestibular examinations consisted of standard pure-tone audiometry, vestibulo-ocular reflex, optokinetic nystagmus, and in some cases the cervico-ocular reflex. Linear regression analysis was used to evaluate progression of hearing impairment, and the degree of hearing impairment of DFNB12 was compared with that found for USH1D. Ophthalmologic examinations consisted of best-corrected visual acuity, Goldmann perimetry, slit-lamp examinations, color vision testing, dark adaptation, electroretinography, electro-oculography, funduscopy and photography of the retina, and sometimes fluorescein angiography.
  
  
  RESULTS
  The USH1D patients had significantly worse hearing impairment than the DFNB12 patients. The DFNB12 patients, identified by missense mutations in CDH23, had normal retinal and vestibular function. All USH1D patients had splice-site mutations in CDH23 and a typical Usher syndrome Type I phenotype. One DFNB12 patient had slightly abnormal yellowish flecks in the posterior poles of both eyes.
  
  
  CONCLUSIONS
  Recessive missense mutations in CDH23 lead to a milder phenotype (DFNB12) than splice-site mutations (USH1D); however, abnormal bilateral flecks, suggestive for lipofuscin accumulation, can be observed in DFNB12 patients.
authors.affiliation: Department of Otorhinolaryngology, UMC St Radboud, Nijmegen, The Netherlands. r.pennings@kno.umcn.nl
authors.forename: Ronald J E
authors.initials: RJ
authors.lastname: Pennings
authors.forename: Vedat
authors.initials: V
authors.lastname: Topsakal
authors.forename: Lisa
authors.initials: L
authors.lastname: Astuto
authors.forename: Arjan P M
authors.initials: AP
authors.lastname: de Brouwer
authors.forename: Mariette
authors.initials: M
authors.lastname: Wagenaar
authors.forename: Patrick L M
authors.initials: PL
authors.lastname: Huygen
authors.forename: William J
authors.initials: WJ
authors.lastname: Kimberling
authors.forename: August F
authors.initials: AF
authors.lastname: Deutman
authors.forename: Hannie
authors.initials: H
authors.lastname: Kremer
authors.forename: Cor W R J
authors.initials: CW
authors.lastname: Cremers
mesh_terms: D000328:Adult; D001301:Audiometry, Pure-Tone; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics*; D003241:Consanguinity; D003941:Diagnostic Techniques, Ophthalmological; D004584:Electronystagmography; D005260:Female; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D012027:Reflex, Vestibulo-Ocular; D012174:Retinitis Pigmentosa / Q000235:genetics*; D013577:Syndrome; D015837:Vestibular Diseases / Q000235:genetics*
chemical_list: C442480:CDH23 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins