Guangqian Xing1, Jun Yao2, Bin Wu3, Tingting Liu1, Qinjun Wei2, Cheng Liu1, Yajie Lu2, Zhibin Chen1, Heng Zheng4, Xiaonan Yang3, Xin Cao2. 1. Department of Otolaryngology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China. 2. Department of Biotechnology, School of Basic Medical Science, Nanjing Medical University, Nanjing, P.R. China. 3. BGI-Shenzhen, Guangdong, P.R. China. 4. Department of Bioinformatics, School of Life Science and Technology, China Pharmaceutical University, Nanjing, P.R. China.
Abstract
PURPOSE: 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. CONCLUSION: 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.
PURPOSE: 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. CONCLUSION: 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: Jun Ling Wang; Xu Yang; Kun Xia; Zheng Mao Hu; Ling Weng; Xin Jin; Hong Jiang; Peng Zhang; Lu Shen; Ji Feng Guo; Nan Li; Ying Rui Li; Li Fang Lei; Jie Zhou; Juan Du; Ya Fang Zhou; Qian Pan; Jian Wang; Jun Wang; Rui Qiang Li; Bei Sha Tang Journal: Brain Date: 2010-11-23 Impact factor: 13.501
Authors: Daoguang Yan; Markku Lehto; Laura Rasilainen; Jari Metso; Christian Ehnholm; Seppo Ylä-Herttuala; Matti Jauhiainen; Vesa M Olkkonen Journal: Arterioscler Thromb Vasc Biol Date: 2007-02-15 Impact factor: 8.311
Authors: Riikka Hynynen; Monika Suchanek; Johanna Spandl; Nils Bäck; Christoph Thiele; Vesa M Olkkonen Journal: J Lipid Res Date: 2009-02-17 Impact factor: 5.922