Variable clinical features in patients with CDH23 mutations (USH1D-DFNB12).
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.
Pennings
Ronald J E
RJ
Department of Otorhinolaryngology, UMC St Radboud, Nijmegen, The Netherlands. r.pennings@kno.umcn.nl
Topsakal
Vedat
V
Astuto
Lisa
L
de Brouwer
Arjan P M
AP
Wagenaar
Mariette
M
Huygen
Patrick L M
PL
Kimberling
William J
WJ
Deutman
August F
AF
Kremer
Hannie
H
Cremers
Cor W R J
CW
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*
C442480:CDH23 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins