Progression of low-frequency sensorineural hearing loss (DFNA6/14-WFS1).
OBJECTIVE
To assess the audiometric profile and speech recognition characteristics in affected members of 2 families with DFNA6/14 harboring heterozygous mutations in the WFS1 gene that cause an autosomal dominant nonsyndromic sensorineural hearing impairment trait.


METHODS
Family study.


METHODS
Tertiary referral center. Patients Thirteen patients from 2 recently identified Dutch families with DFNA6/14 (Dutch III and IV).


METHODS
Cross-sectional and longitudinal analyses of pure-tone thresholds at octave frequencies of 0.25 to 8 kHz were performed, and speech phoneme recognition scores were assessed. Progression was evaluated by linear regression analysis with and without correction for presbycusis.


RESULTS
All individuals showed low-frequency hearing impairment. The 2-kHz frequency was more affected in the Dutch III family than in the Dutch IV family. Progressive hearing loss beyond presbycusis was found in the Dutch IV family and in 3 individuals in the Dutch III family. Annual threshold deterioration was between 0.6 and 1 dB per year at all frequencies. The speech recognition scores in the Dutch III family showed significantly more deterioration at increasing levels of hearing impairment compared with those in the Dutch IV family.


CONCLUSIONS
Both families showed an autosomal dominant, progressive, low-frequency sensorineural hearing impairment caused by heterozygous WFS1 mutations.
Pennings
Ronald J E
RJ
Department of Otorhinolaryngology, University Medical Centre St Radboud, Nijmegen, The Netherlands. r.pennings@kno.azn.nl
Bom
Steven J H
SJ
Cryns
Kim
K
Flothmann
Kris
K
Huygen
Patrick L M
PL
Kremer
Hannie
H
Van Camp
Guy
G
Cremers
Cor W R J
CW
D000293:Adolescent; D000328:Adult; D000368:Aged; D001301:Audiometry, Pure-Tone; D001302:Audiometry, Speech; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000503:physiopathology*; D006579:Heterozygote; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D012720:Severity of Illness Index
D008565:Membrane Proteins; C114987:wolframin protein