Cargando…

Whole exome sequencing identifies a KCNJ12 mutation as a cause of familial dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is characterized by left ventricular dilation, and is associated with systolic dysfunction and increased action potential duration. Approximately 50% of DCM cases are caused by inherited gene mutations with genetic and phenotypic heterogeneity. Next generation sequencing...

Descripción completa

Detalles Bibliográficos
Autores principales: Yuan, Hai-Xin, Yan, Kai, Hou, Dong-Yan, Zhang, Zhi-Yong, Wang, Hua, Wang, Xin, Zhang, Juan, Xu, Xiao-Rong, Liang, Yan-Hong, Zhao, Wen-Shu, Xu, Lin, Zhang, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571686/
https://www.ncbi.nlm.nih.gov/pubmed/28816949
http://dx.doi.org/10.1097/MD.0000000000007727
_version_ 1783259393087766528
author Yuan, Hai-Xin
Yan, Kai
Hou, Dong-Yan
Zhang, Zhi-Yong
Wang, Hua
Wang, Xin
Zhang, Juan
Xu, Xiao-Rong
Liang, Yan-Hong
Zhao, Wen-Shu
Xu, Lin
Zhang, Lin
author_facet Yuan, Hai-Xin
Yan, Kai
Hou, Dong-Yan
Zhang, Zhi-Yong
Wang, Hua
Wang, Xin
Zhang, Juan
Xu, Xiao-Rong
Liang, Yan-Hong
Zhao, Wen-Shu
Xu, Lin
Zhang, Lin
author_sort Yuan, Hai-Xin
collection PubMed
description Dilated cardiomyopathy (DCM) is characterized by left ventricular dilation, and is associated with systolic dysfunction and increased action potential duration. Approximately 50% of DCM cases are caused by inherited gene mutations with genetic and phenotypic heterogeneity. Next generation sequencing may be useful in screening unknown mutations in such cases. A family was identified with DCM, in which the affected family members developed heart failure, arrhythmia, and sudden death. Probands and 4 affected family members underwent whole exome sequencing (WES), bioinformatics methods, and gene annotation to identify potentially causative variants. The Sanger sequencing method was used to verify the candidate mutation. WES yielded 2,238,831 variations. KCNJ12 (p.Glu334del) was identified as a candidate mutation, and the heterozygous mutation was verified by Sanger sequencing. Our study emphasizes the application of WES in identifying causative mutations in DCM. This report is the first to describe the KCNJ12 gene as a cause of DCM in patients.
format Online
Article
Text
id pubmed-5571686
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Wolters Kluwer Health
record_format MEDLINE/PubMed
spelling pubmed-55716862017-09-07 Whole exome sequencing identifies a KCNJ12 mutation as a cause of familial dilated cardiomyopathy Yuan, Hai-Xin Yan, Kai Hou, Dong-Yan Zhang, Zhi-Yong Wang, Hua Wang, Xin Zhang, Juan Xu, Xiao-Rong Liang, Yan-Hong Zhao, Wen-Shu Xu, Lin Zhang, Lin Medicine (Baltimore) 3400 Dilated cardiomyopathy (DCM) is characterized by left ventricular dilation, and is associated with systolic dysfunction and increased action potential duration. Approximately 50% of DCM cases are caused by inherited gene mutations with genetic and phenotypic heterogeneity. Next generation sequencing may be useful in screening unknown mutations in such cases. A family was identified with DCM, in which the affected family members developed heart failure, arrhythmia, and sudden death. Probands and 4 affected family members underwent whole exome sequencing (WES), bioinformatics methods, and gene annotation to identify potentially causative variants. The Sanger sequencing method was used to verify the candidate mutation. WES yielded 2,238,831 variations. KCNJ12 (p.Glu334del) was identified as a candidate mutation, and the heterozygous mutation was verified by Sanger sequencing. Our study emphasizes the application of WES in identifying causative mutations in DCM. This report is the first to describe the KCNJ12 gene as a cause of DCM in patients. Wolters Kluwer Health 2017-08-18 /pmc/articles/PMC5571686/ /pubmed/28816949 http://dx.doi.org/10.1097/MD.0000000000007727 Text en Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc. http://creativecommons.org/licenses/by-nc-nd/4.0 This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0
spellingShingle 3400
Yuan, Hai-Xin
Yan, Kai
Hou, Dong-Yan
Zhang, Zhi-Yong
Wang, Hua
Wang, Xin
Zhang, Juan
Xu, Xiao-Rong
Liang, Yan-Hong
Zhao, Wen-Shu
Xu, Lin
Zhang, Lin
Whole exome sequencing identifies a KCNJ12 mutation as a cause of familial dilated cardiomyopathy
title Whole exome sequencing identifies a KCNJ12 mutation as a cause of familial dilated cardiomyopathy
title_full Whole exome sequencing identifies a KCNJ12 mutation as a cause of familial dilated cardiomyopathy
title_fullStr Whole exome sequencing identifies a KCNJ12 mutation as a cause of familial dilated cardiomyopathy
title_full_unstemmed Whole exome sequencing identifies a KCNJ12 mutation as a cause of familial dilated cardiomyopathy
title_short Whole exome sequencing identifies a KCNJ12 mutation as a cause of familial dilated cardiomyopathy
title_sort whole exome sequencing identifies a kcnj12 mutation as a cause of familial dilated cardiomyopathy
topic 3400
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571686/
https://www.ncbi.nlm.nih.gov/pubmed/28816949
http://dx.doi.org/10.1097/MD.0000000000007727
work_keys_str_mv AT yuanhaixin wholeexomesequencingidentifiesakcnj12mutationasacauseoffamilialdilatedcardiomyopathy
AT yankai wholeexomesequencingidentifiesakcnj12mutationasacauseoffamilialdilatedcardiomyopathy
AT houdongyan wholeexomesequencingidentifiesakcnj12mutationasacauseoffamilialdilatedcardiomyopathy
AT zhangzhiyong wholeexomesequencingidentifiesakcnj12mutationasacauseoffamilialdilatedcardiomyopathy
AT wanghua wholeexomesequencingidentifiesakcnj12mutationasacauseoffamilialdilatedcardiomyopathy
AT wangxin wholeexomesequencingidentifiesakcnj12mutationasacauseoffamilialdilatedcardiomyopathy
AT zhangjuan wholeexomesequencingidentifiesakcnj12mutationasacauseoffamilialdilatedcardiomyopathy
AT xuxiaorong wholeexomesequencingidentifiesakcnj12mutationasacauseoffamilialdilatedcardiomyopathy
AT liangyanhong wholeexomesequencingidentifiesakcnj12mutationasacauseoffamilialdilatedcardiomyopathy
AT zhaowenshu wholeexomesequencingidentifiesakcnj12mutationasacauseoffamilialdilatedcardiomyopathy
AT xulin wholeexomesequencingidentifiesakcnj12mutationasacauseoffamilialdilatedcardiomyopathy
AT zhanglin wholeexomesequencingidentifiesakcnj12mutationasacauseoffamilialdilatedcardiomyopathy