Exome Sequencing and Linkage Analysis Identified Tenascin-C (TNC) as a Novel Causative Gene in Nonsyndromic Hearing Loss

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	Exome Sequencing and Linkage Analysis Identified Tenascin-C (TNC) as a Novel Causative Gene in Nonsyndromic Hearing Loss
	Zhao, Yali 1; Zhao, Feifan 1; Zong, Liang 1; Zhang, Peng 2; Guan, Liping 2; Zhang, Jianguo 2,3; Wang, Dayong 1; Wang, Jing4 ; Chai, Wei 5; Lan, Lan 1
刊名	PLOS ONE
	2013
卷号	8 期号:7
ISSN号	1932-6203
通讯作者	Wang, QJ (reprint author), Chinese Peoples Liberat Army Gen Hosp, Inst Otolaryngol, Dept Otorhinolaryngol Head & Neck Surg, Beijing, Peoples R China.
产权排序	4
英文摘要	In this study, a five-generation Chinese family (family F013) with progressive autosomal dominant hearing loss was mapped to a critical region spanning 28.54 Mb on chromosome 9q31.3-q34.3 by linkage analysis, which was a novel DFNA locus, assigned as DFNA56. In this interval, there were 398 annotated genes. Then, whole exome sequencing was applied in three patients and one normal individual from this family. Six single nucleotide variants and two indels were found co-segregated with the phenotypes. Then using mass spectrum (Sequenom, Inc.) to rank the eight sites, we found only the TNC gene be co-segregated with hearing loss in 53 subjects of F013. And this missense mutation (c.5317G>A, p.V1773M) of TNC located exactly in the critical linked interval. Further screening to the coding region of this gene in 587 subjects with nonsyndromic hearing loss (NSHL) found a second missense mutation, c.5368A>T (p. T1796S), co-segregating with phenotype in the other family. These two mutations located in the conserved region of TNC and were absent in the 387 normal hearing individuals of matched geographical ancestry. Functional effects of the two mutations were predicted using SIFT and both mutations were deleterious. All these results supported that TNC may be the causal gene for the hearing loss inherited in these families. TNC encodes tenascin-C, a member of the extracellular matrix (ECM), is present in the basilar membrane (BM), and the osseous spiral lamina of the cochlea. It plays an important role in cochlear development. The up-regulated expression of TNC gene in tissue repair and neural regeneration was seen in human and zebrafish, and in sensory receptor recovery in the vestibular organ after ototoxic injury in birds. Then the absence of normal tenascin-C was supposed to cause irreversible injuries in cochlea and caused hearing loss.
学科主题	Physiological psychology/Biological Psychology
收录类别	SCI
项目简介	This work was supported by the grants of the National Natural Science Foundation of China, Major Project, No. 81120108009 and National Natural Science Foundation of Youth Science Foundation No.81100719. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
原文出处	http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728356/pdf/pone.0069549.pdf
语种	英语
WOS记录号	WOS:000323114200039
内容类型	期刊论文
源URL	[http://ir.psych.ac.cn/handle/311026/10629]
专题	心理研究所_中国科学院心理健康重点实验室
作者单位	1.Chinese Peoples Liberat Army Gen Hosp, Inst Otolaryngol, Dept Otorhinolaryngol Head & Neck Surg, Beijing, Peoples R China 2.BGI Shenzhen, Shenzhen, Peoples R China 3.Fudan Univ, T Life Res Ctr, Shanghai 200433, Peoples R China 4.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China 5.Chinese Peoples Liberat Army Gen Hosp, Dept Orthopaed Surg, Beijing, Peoples R China 6.BGI Tianjin, Tianjin, Peoples R China 7.S China Univ Technol, Sch Biosci & Biotechnol, Guangzhou, Guangdong, Peoples R China 8.China Agr Univ, Coll Biol Sci, State Key Lab AgroBiotechnol, Beijing 100094, Peoples R China 9.Chinese Peoples Liberat Army Gen Hosp, Inst Life Sci, Beijing, Peoples R China 10.Coll France, F-75231 Paris, France
推荐引用方式 GB/T 7714	Zhao, Yali,Zhao, Feifan,Zong, Liang,et al. Exome Sequencing and Linkage Analysis Identified Tenascin-C (TNC) as a Novel Causative Gene in Nonsyndromic Hearing Loss[J]. PLOS ONE,2013,8(7).
APA	Zhao, Yali.,Zhao, Feifan.,Zong, Liang.,Zhang, Peng.,Guan, Liping.,...&Wang, Qiuju.(2013).Exome Sequencing and Linkage Analysis Identified Tenascin-C (TNC) as a Novel Causative Gene in Nonsyndromic Hearing Loss.PLOS ONE,8(7).
MLA	Zhao, Yali,et al."Exome Sequencing and Linkage Analysis Identified Tenascin-C (TNC) as a Novel Causative Gene in Nonsyndromic Hearing Loss".PLOS ONE 8.7(2013).