title: Targeted Exome Sequencing of Deafness Genes After Failure of Auditory Phenotype-Driven Candidate Gene Screening.
abstract: OBJECTIVE
  To demonstrate the efficacy and advantages of targeted exome sequencing (TES) of known deafness genes in cases with failed or misleading auditory phenotype-driven candidate gene screening.
  
  
  METHODS
  Prospective cohort survey.
  
  
  METHODS
  Otolaryngology department of a tertiary referral hospital.
  
  
  METHODS
  Six hearing-impaired probands with seemingly non-syndromic features from six deaf families were enrolled in this study after failure of genetic diagnosis using auditory phenotype-driven candidate gene screening.
  
  
  METHODS
  TES of known deafness genes was performed in the six probands, and a final causative variant was pursued using subsequent filtering steps.
  
  
  METHODS
  Potential causative variants determined using TES were confirmed by previously introduced filtering steps.
  
  
  RESULTS
  We detected causative variants in three (50%) of six families, and these variants were in the COCH, PAX3, and GJB2 genes. Additionally, we also recapitulated the recent finding from other report arguing for the non-pathogenic potential of MYO1A variant.
  
  
  CONCLUSIONS
  TES of a deafness panel provides a comprehensive genetic screening tool that can be implemented without being misled by the audiogram configuration information and can complement incomplete clinical physical examinations. In addition, the secondary incidental finding obtained by TES contributes useful information regarding the deafness field.
authors.affiliation: *Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul; †Department of Otorhinolaryngology-Head and Neck Surgery, Dankook University Hospital, Cheonan; ‡Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul; §Department of Molecular and Cellular Biology, Sungkyunkwan University School of Medicine, Suwon; ∥Samsung Genome Institute, Samsung Medical Center, Seoul; and ¶Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Bong Jik
authors.initials: BJ
authors.lastname: Kim
authors.forename: Ah Reum
authors.initials: AR
authors.lastname: Kim
authors.forename: Gibeom
authors.initials: G
authors.lastname: Park
authors.forename: Woong Yang
authors.initials: WY
authors.lastname: Park
authors.forename: Sun O
authors.initials: SO
authors.lastname: Chang
authors.forename: Seung-Ha
authors.initials: SH
authors.lastname: Oh
authors.forename: Byung Yoon
authors.initials: BY
authors.lastname: Choi
mesh_terms: D015331:Cohort Studies; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D003638:Deafness / Q000235:genetics* / Q000503:physiopathology; D059472:Exome / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005799:Genes, Dominant; D005820:Genetic Testing / Q000379:methods*; D014644:Genetic Variation; D006309:Hearing / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D011446:Prospective Studies
chemical_list: C110668:COCH protein, human; D017630:Connexins; D016326:Extracellular Matrix Proteins; C000607042:GJB2 protein, human; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D000072259:Connexin 26