Clinical characteristics and determinants of the phenotype in TMEM43 arrhythmogenic right ventricular cardiomyopathy type 5.
Arrhythmogenic right ventricular cardiomyopathy type V (ARVC-5) is the most aggressive heterozygous form of ARVC. It is predominantly caused by a fully penetrant mutation (p.S358L) in the nondesmosomal gene TMEM43-endemic to Newfoundland, Canada. To date, all familial cases reported worldwide share...
Published in: | Heart Rhythm |
---|---|
Main Authors: | , , , , , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
2020
|
Subjects: | |
Online Access: | http://hdl.handle.net/10668/15114 https://doi.org/10.1016/j.hrthm.2020.01.035 http://ddfv.ufv.es/bitstream/10641/1962/1/3.-%20Clinical%20characteristics%20and%20determinants.pdf |
id |
ftsspa:oai:www.repositoriosalud.es:10668/15114 |
---|---|
record_format |
openpolar |
spelling |
ftsspa:oai:www.repositoriosalud.es:10668/15114 2023-11-12T04:21:18+01:00 Clinical characteristics and determinants of the phenotype in TMEM43 arrhythmogenic right ventricular cardiomyopathy type 5. Dominguez, Fernando Zorio, Esther Jimenez-Jaimez, Juan Salguero-Bodes, Rafael Zwart, Robert Gonzalez-Lopez, Esther Molina, Pilar Bermúdez-Jiménez, Francisco Delgado, Juan F Braza-Boïls, Aitana Bornstein, Belen Toquero, Jorge Segovia, Javier Van Tintelen, J Peter Lara-Pezzi, Enrique Garcia-Pavia, Pablo 2020-02-13 http://hdl.handle.net/10668/15114 https://doi.org/10.1016/j.hrthm.2020.01.035 http://ddfv.ufv.es/bitstream/10641/1962/1/3.-%20Clinical%20characteristics%20and%20determinants.pdf en eng http://hdl.handle.net/10668/15114 32062046 doi:10.1016/j.hrthm.2020.01.035 1556-3871 http://ddfv.ufv.es/bitstream/10641/1962/1/3.-%20Clinical%20characteristics%20and%20determinants.pdf Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Arrhythmia Arrhythmogenic right ventricular cardiomyopathy Exercise Genetics TMEM43 Adult Arrhythmogenic Right Ventricular Dysplasia DNA DNA Mutational Analysis Electrocardiography Female Humans Male Membrane Proteins Mutation Missense Pedigree Phenotype Stroke Volume Ventricular Function Left research article VoR 2020 ftsspa https://doi.org/10.1016/j.hrthm.2020.01.035 2023-10-29T17:33:07Z Arrhythmogenic right ventricular cardiomyopathy type V (ARVC-5) is the most aggressive heterozygous form of ARVC. It is predominantly caused by a fully penetrant mutation (p.S358L) in the nondesmosomal gene TMEM43-endemic to Newfoundland, Canada. To date, all familial cases reported worldwide share a common ancestral haplotype. It is unknown whether the p.S358L mutation by itself causes ARVC-5 or whether the disease is influenced by genetic or environmental factors. The purpose of this study was to examine the phenotype, clinical course, and the impact of exercise on patients with p.S358L ARVC-5 without the Newfoundland genetic background. We studied 62 affected individuals and 73 noncarriers from 3 TMEM43-p.S358L Spanish families. The impact of physical activity on the phenotype was also evaluated. Haplotype analysis revealed that the 3 Spanish families were unrelated to patients with ARVC-5 with the Newfoundland genetic background. Two families shared 10 microsatellite markers in a 4.9 cM region surrounding TMEM43; the third family had a distinct haplotype. The affected individuals showed a 38.7% incidence of sudden cardiac death, which was higher in men. Left ventricular involvement was common, with 40% of mutation carriers showing a left ventricular ejection fraction of ARVC-5 is associated with a high risk of sudden cardiac death and characteristic clinical and electrocardiographic features irrespective of geographical origin and genetic background. Our data suggest that, as in desmosomal ARVC, vigorous physical activity could aggravate the phenotype of TMEM43 mutation carriers. Article in Journal/Newspaper Newfoundland Sistema Sanitario Público de Andalucía (SSPA): Repositorio Canada Heart Rhythm 17 6 945 954 |
institution |
Open Polar |
collection |
Sistema Sanitario Público de Andalucía (SSPA): Repositorio |
op_collection_id |
ftsspa |
language |
English |
topic |
Arrhythmia Arrhythmogenic right ventricular cardiomyopathy Exercise Genetics TMEM43 Adult Arrhythmogenic Right Ventricular Dysplasia DNA DNA Mutational Analysis Electrocardiography Female Humans Male Membrane Proteins Mutation Missense Pedigree Phenotype Stroke Volume Ventricular Function Left |
spellingShingle |
Arrhythmia Arrhythmogenic right ventricular cardiomyopathy Exercise Genetics TMEM43 Adult Arrhythmogenic Right Ventricular Dysplasia DNA DNA Mutational Analysis Electrocardiography Female Humans Male Membrane Proteins Mutation Missense Pedigree Phenotype Stroke Volume Ventricular Function Left Dominguez, Fernando Zorio, Esther Jimenez-Jaimez, Juan Salguero-Bodes, Rafael Zwart, Robert Gonzalez-Lopez, Esther Molina, Pilar Bermúdez-Jiménez, Francisco Delgado, Juan F Braza-Boïls, Aitana Bornstein, Belen Toquero, Jorge Segovia, Javier Van Tintelen, J Peter Lara-Pezzi, Enrique Garcia-Pavia, Pablo Clinical characteristics and determinants of the phenotype in TMEM43 arrhythmogenic right ventricular cardiomyopathy type 5. |
topic_facet |
Arrhythmia Arrhythmogenic right ventricular cardiomyopathy Exercise Genetics TMEM43 Adult Arrhythmogenic Right Ventricular Dysplasia DNA DNA Mutational Analysis Electrocardiography Female Humans Male Membrane Proteins Mutation Missense Pedigree Phenotype Stroke Volume Ventricular Function Left |
description |
Arrhythmogenic right ventricular cardiomyopathy type V (ARVC-5) is the most aggressive heterozygous form of ARVC. It is predominantly caused by a fully penetrant mutation (p.S358L) in the nondesmosomal gene TMEM43-endemic to Newfoundland, Canada. To date, all familial cases reported worldwide share a common ancestral haplotype. It is unknown whether the p.S358L mutation by itself causes ARVC-5 or whether the disease is influenced by genetic or environmental factors. The purpose of this study was to examine the phenotype, clinical course, and the impact of exercise on patients with p.S358L ARVC-5 without the Newfoundland genetic background. We studied 62 affected individuals and 73 noncarriers from 3 TMEM43-p.S358L Spanish families. The impact of physical activity on the phenotype was also evaluated. Haplotype analysis revealed that the 3 Spanish families were unrelated to patients with ARVC-5 with the Newfoundland genetic background. Two families shared 10 microsatellite markers in a 4.9 cM region surrounding TMEM43; the third family had a distinct haplotype. The affected individuals showed a 38.7% incidence of sudden cardiac death, which was higher in men. Left ventricular involvement was common, with 40% of mutation carriers showing a left ventricular ejection fraction of ARVC-5 is associated with a high risk of sudden cardiac death and characteristic clinical and electrocardiographic features irrespective of geographical origin and genetic background. Our data suggest that, as in desmosomal ARVC, vigorous physical activity could aggravate the phenotype of TMEM43 mutation carriers. |
format |
Article in Journal/Newspaper |
author |
Dominguez, Fernando Zorio, Esther Jimenez-Jaimez, Juan Salguero-Bodes, Rafael Zwart, Robert Gonzalez-Lopez, Esther Molina, Pilar Bermúdez-Jiménez, Francisco Delgado, Juan F Braza-Boïls, Aitana Bornstein, Belen Toquero, Jorge Segovia, Javier Van Tintelen, J Peter Lara-Pezzi, Enrique Garcia-Pavia, Pablo |
author_facet |
Dominguez, Fernando Zorio, Esther Jimenez-Jaimez, Juan Salguero-Bodes, Rafael Zwart, Robert Gonzalez-Lopez, Esther Molina, Pilar Bermúdez-Jiménez, Francisco Delgado, Juan F Braza-Boïls, Aitana Bornstein, Belen Toquero, Jorge Segovia, Javier Van Tintelen, J Peter Lara-Pezzi, Enrique Garcia-Pavia, Pablo |
author_sort |
Dominguez, Fernando |
title |
Clinical characteristics and determinants of the phenotype in TMEM43 arrhythmogenic right ventricular cardiomyopathy type 5. |
title_short |
Clinical characteristics and determinants of the phenotype in TMEM43 arrhythmogenic right ventricular cardiomyopathy type 5. |
title_full |
Clinical characteristics and determinants of the phenotype in TMEM43 arrhythmogenic right ventricular cardiomyopathy type 5. |
title_fullStr |
Clinical characteristics and determinants of the phenotype in TMEM43 arrhythmogenic right ventricular cardiomyopathy type 5. |
title_full_unstemmed |
Clinical characteristics and determinants of the phenotype in TMEM43 arrhythmogenic right ventricular cardiomyopathy type 5. |
title_sort |
clinical characteristics and determinants of the phenotype in tmem43 arrhythmogenic right ventricular cardiomyopathy type 5. |
publishDate |
2020 |
url |
http://hdl.handle.net/10668/15114 https://doi.org/10.1016/j.hrthm.2020.01.035 http://ddfv.ufv.es/bitstream/10641/1962/1/3.-%20Clinical%20characteristics%20and%20determinants.pdf |
geographic |
Canada |
geographic_facet |
Canada |
genre |
Newfoundland |
genre_facet |
Newfoundland |
op_relation |
http://hdl.handle.net/10668/15114 32062046 doi:10.1016/j.hrthm.2020.01.035 1556-3871 http://ddfv.ufv.es/bitstream/10641/1962/1/3.-%20Clinical%20characteristics%20and%20determinants.pdf |
op_rights |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ open access |
op_doi |
https://doi.org/10.1016/j.hrthm.2020.01.035 |
container_title |
Heart Rhythm |
container_volume |
17 |
container_issue |
6 |
container_start_page |
945 |
op_container_end_page |
954 |
_version_ |
1782336788627456000 |