title: Phenotype of the first otosclerosis family linked to OTSC10.
abstract: OBJECTIVE
  To report on the audiometric findings in the first otosclerosis family linked to OTSC10.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  A family study in a large otosclerosis family was performed, and a pedigree was constructed. Examination of all family members consisted of medical history guided by a questionnaire, pure-tone audiometry, otoscopy, and collection of blood samples for genetic linkage analysis. In addition, a selected group underwent stapedial reflex measurements and tympanometry. Cross-sectional as well as longitudinal analyses of audiometric data were performed.
  
  
  RESULTS
  Eleven family members were identified as clinically affected and were all carriers of the disease haplotype. Twelve clinically unaffected family members carried the disease haplotype as well. Cross-sectional analyses of clinically affected family members showed no significant progression of air conduction (AC) thresholds, bone conduction (BC) thresholds, and air-bone gap (ABG) levels with increasing age. Longitudinal regression analyses in one family member revealed significant deterioration of AC thresholds at all frequencies. The BC thresholds showed a significant increase with advancing age at 0.5 kHz, 2 kHz, and 4 kHz. A significant progression of ABG was seen at 8 kHz.
  
  
  CONCLUSIONS
  The intersubject variation, in terms of age of onset, level of progression, and audiogram configuration, was remarkable, probably due to reduced penetrance and variable expression of the disease. Long-term audiometric data in one patient, however, were useful to demonstrate progression of hearing impairment.
authors: Department of Otorhinolaryngology, Donder's Centre for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands. N.Weegerink@kno.umcn.nl
authors: Nicole J D
authors: NJ
authors: Weegerink
authors: Isabelle
authors: I
authors: Schrauwen
authors: Patrick L M
authors: PL
authors: Huygen
authors: Ronald J E
authors: RJ
authors: Pennings
authors: Cor W R J
authors: CW
authors: Cremers
authors: Guy
authors: G
authors: Van Camp
authors: Henricus P M
authors: HP
authors: Kunst
mesh_terms: D000158:Acoustic Impedance Tests; D000328:Adult; D001301:Audiometry, Pure-Tone; D002869:Chromosome Aberrations; D003430:Cross-Sectional Studies; D005260:Female; D005799:Genes, Dominant; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D056426:Genetic Loci / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010040:Otosclerosis / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D038781:Otoscopy; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D012022:Reflex, Acoustic / Q000235:genetics; D013200:Stapes Mobilization