title: Identification of OSBPL2 as a novel candidate gene for progressive nonsyndromic hearing loss by whole-exome sequencing.
abstract: OBJECTIVE
  Various forms of hearing loss have genetic causes, but many of the responsible genes have not yet been identified. Here, we describe a large seven-generation Chinese family with autosomal dominant nonsyndromic hearing loss that has been excluded as being caused by known deafness gene mutations associated with autosomal dominant nonsyndromic hearing loss with the aim of identifying a novel causative gene involved in deafness.
  
  
  METHODS
  Whole-exome sequencing was conducted in three affected family members, and cosegregation analysis was performed on other members of the family.
  
  
  RESULTS
  Whole-exome sequencing and subsequent segregation analysis identified a heterozygous frameshift mutation (c.153_154delCT, p.Gln53Argfs*100) in the oxysterol binding protein-like 2 (OSBPL2) gene in 25 affected family members. The deletion mutation is predicted to lead to premature truncation of the OSBPL2 protein. Modeling and structure-based analysis support the theory that this gene deletion is functionally deleterious. Our finding was further confirmed by the detection of another missense mutation, a c.583C>A transversion (p.Leu195Met) in exon 7 of OSBPL2, in an additional sporadic case of deafness.
  
  
  CONCLUSIONS
  Based on this study, OSBPL2 was identified as an excellent novel candidate gene for autosomal dominant nonsyndromic hearing loss; this study is the first to implicate OSBPL2 mutations in autosomal dominant nonsyndromic hearing loss.
authors: Department of Otolaryngology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
authors: Guangqian
authors: G
authors: Xing
authors: Department of Biotechnology, School of Basic Medical Science, Nanjing Medical University, Nanjing, P.R. China.
authors: Jun
authors: J
authors: Yao
authors: BGI-Shenzhen, Guangdong, P.R. China.
authors: Bin
authors: B
authors: Wu
authors: Department of Otolaryngology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
authors: Tingting
authors: T
authors: Liu
authors: Department of Biotechnology, School of Basic Medical Science, Nanjing Medical University, Nanjing, P.R. China.
authors: Qinjun
authors: Q
authors: Wei
authors: Department of Otolaryngology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
authors: Cheng
authors: C
authors: Liu
authors: Department of Biotechnology, School of Basic Medical Science, Nanjing Medical University, Nanjing, P.R. China.
authors: Yajie
authors: Y
authors: Lu
authors: Department of Otolaryngology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
authors: Zhibin
authors: Z
authors: Chen
authors: Department of Bioinformatics, School of Life Science and Technology, China Pharmaceutical University, Nanjing, P.R. China.
authors: Heng
authors: H
authors: Zheng
authors: BGI-Shenzhen, Guangdong, P.R. China.
authors: Xiaonan
authors: X
authors: Yang
authors: Department of Biotechnology, School of Basic Medical Science, Nanjing Medical University, Nanjing, P.R. China.
authors: Xin
authors: X
authors: Cao
mesh_terms: D000818:Animals; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D002681:China; D003051:Cochlea / Q000378:metabolism*; D003638:Deafness / Q000235:genetics; D059472:Exome; D005260:Female; D016368:Frameshift Mutation; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D051379:Mice; D020125:Mutation, Missense; D010375:Pedigree; D011987:Receptors, Steroid / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017422:Sequence Analysis, DNA / Q000379:methods*; D000098825:Oxysterol Binding Proteins
chemical_list: D011987:Receptors, Steroid; C461064:OSBPL2 protein, human; D000098825:Oxysterol Binding Proteins