title: Progression of low-frequency sensorineural hearing loss (DFNA6/14-WFS1).
abstract: 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.
authors.affiliation: Department of Otorhinolaryngology, University Medical Centre St Radboud, Nijmegen, The Netherlands. r.pennings@kno.azn.nl
authors.forename: Ronald J E
authors.initials: RJ
authors.lastname: Pennings
authors.forename: Steven J H
authors.initials: SJ
authors.lastname: Bom
authors.forename: Kim
authors.initials: K
authors.lastname: Cryns
authors.forename: Kris
authors.initials: K
authors.lastname: Flothmann
authors.forename: Patrick L M
authors.initials: PL
authors.lastname: Huygen
authors.forename: Hannie
authors.initials: H
authors.lastname: Kremer
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp
authors.forename: Cor W R J
authors.initials: CW
authors.lastname: Cremers
mesh_terms: 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
chemical_list: D008565:Membrane Proteins; C114987:wolframin protein