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Whole-Exome Sequencing to Identify a Novel LMNA Gene Mutation Associated with Inherited Cardiac Conduction Disease

BACKGROUND: Inherited cardiac conduction diseases (CCD) are rare but are caused by mutations in a myriad of genes. Recently, whole-exome sequencing has successfully led to the identification of causal mutations for rare monogenic Mendelian diseases. OBJECTIVE: To investigate the genetic background o...

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Autores principales: Lai, Chun-Chi, Yeh, Yung-Hsin, Hsieh, Wen-Ping, Kuo, Chi-Tai, Wang, Wen-Ching, Chu, Chia-Han, Hung, Chiu-Lien, Cheng, Chia-Yang, Tsai, Hsin-Yi, Lee, Jia-Lin, Tang, Chuan-Yi, Hsu, Lung-An
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3861486/
https://www.ncbi.nlm.nih.gov/pubmed/24349489
http://dx.doi.org/10.1371/journal.pone.0083322
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author Lai, Chun-Chi
Yeh, Yung-Hsin
Hsieh, Wen-Ping
Kuo, Chi-Tai
Wang, Wen-Ching
Chu, Chia-Han
Hung, Chiu-Lien
Cheng, Chia-Yang
Tsai, Hsin-Yi
Lee, Jia-Lin
Tang, Chuan-Yi
Hsu, Lung-An
author_facet Lai, Chun-Chi
Yeh, Yung-Hsin
Hsieh, Wen-Ping
Kuo, Chi-Tai
Wang, Wen-Ching
Chu, Chia-Han
Hung, Chiu-Lien
Cheng, Chia-Yang
Tsai, Hsin-Yi
Lee, Jia-Lin
Tang, Chuan-Yi
Hsu, Lung-An
author_sort Lai, Chun-Chi
collection PubMed
description BACKGROUND: Inherited cardiac conduction diseases (CCD) are rare but are caused by mutations in a myriad of genes. Recently, whole-exome sequencing has successfully led to the identification of causal mutations for rare monogenic Mendelian diseases. OBJECTIVE: To investigate the genetic background of a family affected by inherited CCD. METHODS AND RESULTS: We used whole-exome sequencing to study a Chinese family with multiple family members affected by CCD. Using the pedigree information, we proposed a heterozygous missense mutation (c.G695T, Gly232Val) in the lamin A/C (LMNA) gene as a candidate mutation for susceptibility to CCD in this family. The mutation is novel and is expected to affect the conformation of the coiled-coil rod domain of LMNA according to a structural model prediction. Its pathogenicity in lamina instability was further verified by expressing the mutation in a cellular model. CONCLUSIONS: Our results suggest that whole-exome sequencing is a feasible approach to identifying the candidate genes underlying inherited conduction diseases.
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spelling pubmed-38614862013-12-17 Whole-Exome Sequencing to Identify a Novel LMNA Gene Mutation Associated with Inherited Cardiac Conduction Disease Lai, Chun-Chi Yeh, Yung-Hsin Hsieh, Wen-Ping Kuo, Chi-Tai Wang, Wen-Ching Chu, Chia-Han Hung, Chiu-Lien Cheng, Chia-Yang Tsai, Hsin-Yi Lee, Jia-Lin Tang, Chuan-Yi Hsu, Lung-An PLoS One Research Article BACKGROUND: Inherited cardiac conduction diseases (CCD) are rare but are caused by mutations in a myriad of genes. Recently, whole-exome sequencing has successfully led to the identification of causal mutations for rare monogenic Mendelian diseases. OBJECTIVE: To investigate the genetic background of a family affected by inherited CCD. METHODS AND RESULTS: We used whole-exome sequencing to study a Chinese family with multiple family members affected by CCD. Using the pedigree information, we proposed a heterozygous missense mutation (c.G695T, Gly232Val) in the lamin A/C (LMNA) gene as a candidate mutation for susceptibility to CCD in this family. The mutation is novel and is expected to affect the conformation of the coiled-coil rod domain of LMNA according to a structural model prediction. Its pathogenicity in lamina instability was further verified by expressing the mutation in a cellular model. CONCLUSIONS: Our results suggest that whole-exome sequencing is a feasible approach to identifying the candidate genes underlying inherited conduction diseases. Public Library of Science 2013-12-12 /pmc/articles/PMC3861486/ /pubmed/24349489 http://dx.doi.org/10.1371/journal.pone.0083322 Text en © 2013 Lai et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lai, Chun-Chi
Yeh, Yung-Hsin
Hsieh, Wen-Ping
Kuo, Chi-Tai
Wang, Wen-Ching
Chu, Chia-Han
Hung, Chiu-Lien
Cheng, Chia-Yang
Tsai, Hsin-Yi
Lee, Jia-Lin
Tang, Chuan-Yi
Hsu, Lung-An
Whole-Exome Sequencing to Identify a Novel LMNA Gene Mutation Associated with Inherited Cardiac Conduction Disease
title Whole-Exome Sequencing to Identify a Novel LMNA Gene Mutation Associated with Inherited Cardiac Conduction Disease
title_full Whole-Exome Sequencing to Identify a Novel LMNA Gene Mutation Associated with Inherited Cardiac Conduction Disease
title_fullStr Whole-Exome Sequencing to Identify a Novel LMNA Gene Mutation Associated with Inherited Cardiac Conduction Disease
title_full_unstemmed Whole-Exome Sequencing to Identify a Novel LMNA Gene Mutation Associated with Inherited Cardiac Conduction Disease
title_short Whole-Exome Sequencing to Identify a Novel LMNA Gene Mutation Associated with Inherited Cardiac Conduction Disease
title_sort whole-exome sequencing to identify a novel lmna gene mutation associated with inherited cardiac conduction disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3861486/
https://www.ncbi.nlm.nih.gov/pubmed/24349489
http://dx.doi.org/10.1371/journal.pone.0083322
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