title: Identification of novel OTOF compound heterozygous mutations by targeted next-generation sequencing in a Chinese patient with auditory neuropathy spectrum disorder.
abstract: OBJECTIVE
  The molecular causes of auditory neuropathy spectrum disorder (ANSD) are not well known. Identification of the pathogenic mutations underlying nonsyndromic ANSD is difficult because of its extremely heterogeneous trait. The aim of the present study was to identify the genetic etiology of a single Chinese patient diagnosed with congenital ANSD by targeted next-generation sequencing.
  
  
  METHODS
  Targeted next-generation sequencing of 79 known deafness genes was performed in a child that was clinically diagnosed with ANSD and received cochlear implantation. Candidate pathogenic variants were confirmed by Sanger sequencing. Post-implantation outcome were evaluated in a 40 months span.
  
  
  RESULTS
  Novel compound heterozygous mutations p.R1583H/p.Q1883X in OTOF were identified as the pathogenic cause of the patient, correlated with a good post-implantation outcome in terms of sound detection and communication skills.
  
  
  CONCLUSIONS
  Targeted next-generation sequencing is effective for molecular diagnosis of ANSD and may provide important information for clinical management of this disease.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; Ear Institute, Shanghai Jiaotong University, Shanghai 200092, China.
authors.forename: Lu-ping
authors.initials: LP
authors.lastname: Zhang
authors.forename: Yong-Chuan
authors.initials: YC
authors.lastname: Chai
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
mesh_terms: D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics* / Q000503:physiopathology; D002681:China; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D006313:Hearing Loss, Central / Q000235:genetics* / Q000503:physiopathology; D006579:Heterozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C118457:OTOF protein, human
keywords: Auditory neuropathy; Auditory neuropathy spectrum disorders; Cochlear implantation; Congenital deafness; Mutation; OTOF