Variable clinical features in patients with CDH23 mutations (USH1D-DFNB12)

Ronald J.E. Pennings, Vedat Topsakal, Lisa Astuto, Arjan P.M. De Brouwer, Mariette Wagenaar, Patrick L.M. Huygen, William J. Kimberling, August F. Deutman, Hannie Kremer, Cor W.R.J. Cremers

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objective: To describe the findings of audiovestibular and ophthalmologic examinations in four families with mutations in the CDH23 gene. Study Design: Family study. Setting: Tertiary referral center. Patients: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)699-706
Number of pages8
JournalOtology and Neurotology
Volume25
Issue number5
DOIs
StatePublished - Sep 1 2004

Fingerprint

Mutation
Hearing Loss
Missense Mutation
Usher Syndromes
Optokinetic Nystagmus
Pure-Tone Audiometry
Vestibulo-Ocular Reflex
Dark Adaptation
Phenotype
Electroretinography
Autosomal Recessive 12 Deafness
Lipofuscin
Color Vision
Visual Field Tests
Fluorescein Angiography
Photography
Tertiary Care Centers
Genes
Visual Acuity
Reflex

Keywords

  • CDH23 gene
  • DFNB12
  • Genotype-phenotype correlation
  • Hearing impairment
  • Retinitis pigmentosa
  • USH1D
  • Usher syndrome

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Sensory Systems
  • Clinical Neurology

Cite this

Pennings, R. J. E., Topsakal, V., Astuto, L., De Brouwer, A. P. M., Wagenaar, M., Huygen, P. L. M., ... Cremers, C. W. R. J. (2004). Variable clinical features in patients with CDH23 mutations (USH1D-DFNB12). Otology and Neurotology, 25(5), 699-706. https://doi.org/10.1097/00129492-200409000-00009

Variable clinical features in patients with CDH23 mutations (USH1D-DFNB12). / Pennings, Ronald J.E.; Topsakal, Vedat; Astuto, Lisa; De Brouwer, Arjan P.M.; Wagenaar, Mariette; Huygen, Patrick L.M.; Kimberling, William J.; Deutman, August F.; Kremer, Hannie; Cremers, Cor W.R.J.

In: Otology and Neurotology, Vol. 25, No. 5, 01.09.2004, p. 699-706.

Research output: Contribution to journalArticle

Pennings, RJE, Topsakal, V, Astuto, L, De Brouwer, APM, Wagenaar, M, Huygen, PLM, Kimberling, WJ, Deutman, AF, Kremer, H & Cremers, CWRJ 2004, 'Variable clinical features in patients with CDH23 mutations (USH1D-DFNB12)', Otology and Neurotology, vol. 25, no. 5, pp. 699-706. https://doi.org/10.1097/00129492-200409000-00009
Pennings RJE, Topsakal V, Astuto L, De Brouwer APM, Wagenaar M, Huygen PLM et al. Variable clinical features in patients with CDH23 mutations (USH1D-DFNB12). Otology and Neurotology. 2004 Sep 1;25(5):699-706. https://doi.org/10.1097/00129492-200409000-00009
Pennings, Ronald J.E. ; Topsakal, Vedat ; Astuto, Lisa ; De Brouwer, Arjan P.M. ; Wagenaar, Mariette ; Huygen, Patrick L.M. ; Kimberling, William J. ; Deutman, August F. ; Kremer, Hannie ; Cremers, Cor W.R.J. / Variable clinical features in patients with CDH23 mutations (USH1D-DFNB12). In: Otology and Neurotology. 2004 ; Vol. 25, No. 5. pp. 699-706.
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