Audiometric characteristics of a Dutch family linked to DFNA15 with a novel mutation (p.L289F) in POU4F3.
OBJECTIVE
To report on the audiometric characteristics of a large Dutch family linked to DFNA15 with a novel mutation (p.L289F) in POU4F3 (OMIM 602460).


METHODS
Clinical investigation.


METHODS
Tertiary referral center.


METHODS
Family members from a large 5-generation pedigree with sensorineural hearing impairment segregating as an autosomal dominant trait.


METHODS
Cross-sectional and longitudinal analyses of pure-tone audiometric data, and cross-sectional analyses of speech audiometry data.


RESULTS
Overall, a flat to gently downsloping audiometric configuration was observed with a progression rate of approximately 0.8 dB/y across most frequencies. Speech recognition scores remained fairly good in relation to age and hearing level compared with a group of patients with presbycusis. Interindividual variability was observed in terms of subjective onset age and audiometric configuration. Two mutation carriers, who reported vestibular symptoms, underwent vestibular examination and showed hypofunction of the vestibular labyrinth.


CONCLUSIONS
The audiometric phenotype of the Dutch family linked to DFNA15 with a novel mutation in POU4F3 is comparable to that observed in the original Israeli family linked to DFNA15. Relatively good speech recognition scores suggest outer hair cell involvement. DFNA15 may represent a cochleovestibular disorder.
Pauw
Robert J
RJ
Department of Otorhinolaryngology, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands. R.Pauw@kno.umcn.nl
van Drunen
F J Wendy
FJ
Collin
Rob W J
RW
Huygen
Patrick L M
PL
Kremer
Hannie
H
Cremers
Cor W R J
CW
D000328:Adult; D000368:Aged; D001301:Audiometry, Pure-Tone; D001302:Audiometry, Speech; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005799:Genes, Dominant; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology; D010375:Pedigree; D012044:Regression Analysis; D050821:Transcription Factor Brn-3C / Q000235:genetics*
D018398:Homeodomain Proteins; C111223:POU4F3 protein, human; D050821:Transcription Factor Brn-3C