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Investigation of Pathogenic Genes in Chinese sporadic Hypertrophic Cardiomyopathy Patients by Whole Exome Sequencing
Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease with high heterogeneity. Limited knowledge concerning the genetic background of nearly 40% HCM cases indicates there is a clear need for further investigation to explore the genetic pathogenesis of the disease. In this study, we undertook...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647833/ https://www.ncbi.nlm.nih.gov/pubmed/26573135 http://dx.doi.org/10.1038/srep16609 |
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author | Xu, Jing Li, Zhongshan Ren, Xianguo Dong, Ming Li, Jinxin Shi, Xingjuan Zhang, Yu Xie, Wei Sun, Zhongsheng Liu, Xiangdong Dai, Qiming |
author_facet | Xu, Jing Li, Zhongshan Ren, Xianguo Dong, Ming Li, Jinxin Shi, Xingjuan Zhang, Yu Xie, Wei Sun, Zhongsheng Liu, Xiangdong Dai, Qiming |
author_sort | Xu, Jing |
collection | PubMed |
description | Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease with high heterogeneity. Limited knowledge concerning the genetic background of nearly 40% HCM cases indicates there is a clear need for further investigation to explore the genetic pathogenesis of the disease. In this study, we undertook a whole exome sequencing (WES) approach to identify novel candidate genes and mutations associated with HCM. The cohort consisted of 74 unrelated patients with sporadic HCM (sHCM) previously determined to be negative for mutations in eight sarcomere genes. The results showed that 7 of 74 patients (9.5%) had damaging mutations in 43 known HCM disease genes. Furthermore, after analysis combining the Transmission and De novo Association (TADA) program and the ToppGene program, 10 putative genes gained priority. A thorough review of public databases and related literature revealed that there is strong supporting evidence for most of the genes playing roles in various aspects of heart development. Findings from recent studies suggest that the putative and known disease genes converge on three functional pathways: sarcomere function, calcium signaling and metabolism pathway. This study illustrates the benefit of WES, in combination with rare variant analysis tools, in providing valuable insight into the genetic etiology of a heterogeneous sporadic disease. |
format | Online Article Text |
id | pubmed-4647833 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46478332015-11-23 Investigation of Pathogenic Genes in Chinese sporadic Hypertrophic Cardiomyopathy Patients by Whole Exome Sequencing Xu, Jing Li, Zhongshan Ren, Xianguo Dong, Ming Li, Jinxin Shi, Xingjuan Zhang, Yu Xie, Wei Sun, Zhongsheng Liu, Xiangdong Dai, Qiming Sci Rep Article Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease with high heterogeneity. Limited knowledge concerning the genetic background of nearly 40% HCM cases indicates there is a clear need for further investigation to explore the genetic pathogenesis of the disease. In this study, we undertook a whole exome sequencing (WES) approach to identify novel candidate genes and mutations associated with HCM. The cohort consisted of 74 unrelated patients with sporadic HCM (sHCM) previously determined to be negative for mutations in eight sarcomere genes. The results showed that 7 of 74 patients (9.5%) had damaging mutations in 43 known HCM disease genes. Furthermore, after analysis combining the Transmission and De novo Association (TADA) program and the ToppGene program, 10 putative genes gained priority. A thorough review of public databases and related literature revealed that there is strong supporting evidence for most of the genes playing roles in various aspects of heart development. Findings from recent studies suggest that the putative and known disease genes converge on three functional pathways: sarcomere function, calcium signaling and metabolism pathway. This study illustrates the benefit of WES, in combination with rare variant analysis tools, in providing valuable insight into the genetic etiology of a heterogeneous sporadic disease. Nature Publishing Group 2015-11-17 /pmc/articles/PMC4647833/ /pubmed/26573135 http://dx.doi.org/10.1038/srep16609 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Xu, Jing Li, Zhongshan Ren, Xianguo Dong, Ming Li, Jinxin Shi, Xingjuan Zhang, Yu Xie, Wei Sun, Zhongsheng Liu, Xiangdong Dai, Qiming Investigation of Pathogenic Genes in Chinese sporadic Hypertrophic Cardiomyopathy Patients by Whole Exome Sequencing |
title | Investigation of Pathogenic Genes in Chinese sporadic Hypertrophic Cardiomyopathy Patients by Whole Exome Sequencing |
title_full | Investigation of Pathogenic Genes in Chinese sporadic Hypertrophic Cardiomyopathy Patients by Whole Exome Sequencing |
title_fullStr | Investigation of Pathogenic Genes in Chinese sporadic Hypertrophic Cardiomyopathy Patients by Whole Exome Sequencing |
title_full_unstemmed | Investigation of Pathogenic Genes in Chinese sporadic Hypertrophic Cardiomyopathy Patients by Whole Exome Sequencing |
title_short | Investigation of Pathogenic Genes in Chinese sporadic Hypertrophic Cardiomyopathy Patients by Whole Exome Sequencing |
title_sort | investigation of pathogenic genes in chinese sporadic hypertrophic cardiomyopathy patients by whole exome sequencing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647833/ https://www.ncbi.nlm.nih.gov/pubmed/26573135 http://dx.doi.org/10.1038/srep16609 |
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