A Novel Mutation Identified in the DFNA5 Gene in a Dutch Family: A Clinical and Genetic EvaluationBischoff A.M.L.C. · Luijendijk M.W.J. · Huygen P.L.M. · van Duijnhoven G. · De Leenheer E.M.R. · Oudesluijs G.G. · van Laer L. · Cremers F.P.M. · Cremers C.W.R.J. · Kremer H.
Departments of aOtorhinolaryngology and bHuman Genetics, University Medical Centre Nijmegen, Nijmegen, TheNetherlands; cDepartment of Medical Genetics, University of Antwerp, Belgium
A novel DFNA5 mutation was found in a Dutch family, of which 37 members were examined. A nucleotide substitution was identified in the splice acceptor site of intron 7, leading to skipping of exon 8 in part of the transcripts. The mutation was found in 18 individuals. Sensorineural hearing impairment was non-syndromic and symmetric. In early life, presumably congenitally, hearing impairment amounted to 30 dB in the high frequencies. Progression was most pronounced at 1 kHz (1.8 dB/year). Speech recognition was relatively good with a phoneme score of about 50% at the age of 70. Onset age was 37 years, and recognition deteriorated by 1.3% per year. The recognition score deteriorated by 1.0% per decibel threshold increase from a mean pure-tone average (PTA at 1, 2 and 4 kHz) of 63 dB onwards. Vestibular function was generally normal. The second mutation identified in the DFNA5 gene results in hearing impairment, similar to that in the original DFNA5 family in terms of pure-tone thresholds, but with more favourable speech recognition.
Department of Otorhinolaryngology, UMCN
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A.M.L.C.B. and M.W.J.L. contributed equally to this work.
Received: December 9, 2002
Accepted after revision: July 3, 2003
Number of Print Pages : 13
Number of Figures : 8, Number of Tables : 1, Number of References : 35
Audiology & Neuro-Otology (Basic Research and Clinical Applications)
Vol. 9, No. 1, Year 2004 (Cover Date: January-February 2004)
Journal Editor: Manfried Hoke, Münster, Germany
ISSN: 1420–3030 (print), 1421–9700 (Online)
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