A novel mutation identified in the DFNA5 gene in a Dutch family: a clinical and genetic evaluation.
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.
Bischoff
Anne M L C
AM
Department of Otorhinolaryngology, University Medical Centre Nijmegen, Nijmegen, The Netherlands. a.bischoff@kno.umcn.nl
Luijendijk
Mirjam W J
MW
Huygen
Patrick L M
PL
van Duijnhoven
Gerard
G
De Leenheer
Els M R
EM
Oudesluijs
Grétel G
GG
Van Laer
Lut
L
Cremers
Frans P M
FP
Cremers
Cor W R J
CW
Kremer
Hannie
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D001301:Audiometry, Pure-Tone; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011960:Receptors, Estrogen; D013063:Speech Discrimination Tests; D014057:Tomography, X-Ray Computed; D014724:Vestibular Function Tests; D000094524:Gasdermins
D002352:Carrier Proteins; D011960:Receptors, Estrogen; C111432:GSDME protein, human; D000094524:Gasdermins