title: Audioprofile-directed successful mutation analysis in a DFNA2/KCNQ4 (p.Leu274His) family.
abstract: OBJECTIVE
  We undertook to show that in a family with nonsyndromic autosomal dominant sensorineural hearing loss, genetic analysis can be successful when there is a match with a specific DFNA audioprofile. We also provide an update of relevant DFNA2/KCNQ4 audioprofiles and report the results of automatic audioprofile analysis using the Internet program AudioGene.
  
  
  METHODS
  Audiometric data and blood samples were obtained from the family W08-0384. Based on the audiograms of the affected participants, mutation analysis of KCNQ4 was started. Original audiometric threshold data were collected for all identified KCNQ4-related DFNA2 families. The Internet computer program AudioGene, recently developed for automatic audioprofile analysis, was accessed.
  
  
  RESULTS
  The family's audioprofile and the program AudioGene predicted the DFNA2/KCNQ4 locus. Mutation analysis of KCNQ4 revealed a c.821T>A (p.Leu274His) mutation of the KCNQ4 gene. This mutation has been previously identified in a Dutch family. Genetic analysis revealed a common haplotype in these two families over a region including the KCNQ4 gene.
  
  
  CONCLUSIONS
  Familiarity with the audioprofiles of DFNA traits may lead to successful mutation analysis of the gene involved, even in a small family in which genetic linkage analysis is not an option. Alternatively, the specially developed program AudioGene can be accessed on the Internet to perform automatic audioprofile analysis of a family's (audiological) phenotype.
authors.affiliation: Department of Otorhinolaryngology-Raboud University Nijmegen Medical Center, Clinical Neuroscience Donders Center for Brain, Cognition and Behavior, Nijmegen, The Netherlands.
authors.forename: Anne-Martine R
authors.initials: AM
authors.lastname: de Heer
authors.forename: Margit
authors.initials: M
authors.lastname: Schraders
authors.forename: Jaap
authors.initials: J
authors.lastname: Oostrik
authors.forename: Lies
authors.initials: L
authors.lastname: Hoefsloot
authors.forename: Patrick L M
authors.initials: PL
authors.lastname: Huygen
authors.forename: Cor W R J
authors.initials: CW
authors.lastname: Cremers
mesh_terms: D001301:Audiometry, Pure-Tone; D004252:DNA Mutational Analysis; D005799:Genes, Dominant; D006239:Haplotypes; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D051656:KCNQ Potassium Channels / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D009426:Netherlands; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012984:Software
chemical_list: D051656:KCNQ Potassium Channels; C117367:KCNQ4 protein, human