Exome sequencing and linkage analysis identified Tenascin-C (TNC) as a novel causative gene in nonsyndromic hearing loss

Zhao, Yali, Zhao, Feifan, Zong, Liang, Zhang, Peng, Guan, Liping, Zhang, Jianguo, Wang, Dayong, Wang, Jing, Chai, Wei, Lan, Lan, Li, Qian, Han, Bing, Yang, Ling, Jin, Xin, Yang, Weiyan, Hu, Xiaoxiang, Wang, Xiaoning, Li, Ning, Li, Yingrui, Petit, Christine, Wang, Jun, Yang, Huanming, Wang, Jian and 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: . doi:10.1371/journal.pone.0069549


Author Zhao, Yali
Zhao, Feifan
Zong, Liang
Zhang, Peng
Guan, Liping
Zhang, Jianguo
Wang, Dayong
Wang, Jing
Chai, Wei
Lan, Lan
Li, Qian
Han, Bing
Yang, Ling
Jin, Xin
Yang, Weiyan
Hu, Xiaoxiang
Wang, Xiaoning
Li, Ning
Li, Yingrui
Petit, Christine
Wang, Jun
Yang, Huanming
Wang, Jian
Wang, Qiuju
Title Exome sequencing and linkage analysis identified Tenascin-C (TNC) as a novel causative gene in nonsyndromic hearing loss
Formatted title
Exome sequencing and linkage analysis identified Tenascin-C (TNC) as a novel causative gene in nonsyndromic hearing loss
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-07-30
Sub-type Article (original research)
DOI 10.1371/journal.pone.0069549
Open Access Status DOI
Volume 8
Issue 7
Total pages 8
Place of publication San Francisco, United States
Publisher Public Library of Science
Language eng
Abstract 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 16 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 18 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 01 Sep 2015, 12:53:47 EST by System User on behalf of Learning and Research Services (UQ Library)