Clinical characteristics and determinants of phenotype in TMEM43 Arrhythmogenic right ventricular cardiomyopathy type 5.
Background 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 world...
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Heart Rhythm
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Online Access: | http://hdl.handle.net/10641/1962 https://doi.org/10.1016/j.hrthm.2020.01.035 |
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ftunivfdv:oai:ddfv.ufv.es:10641/1962 2023-05-15T17:21:23+02:00 Clinical characteristics and determinants of phenotype in TMEM43 Arrhythmogenic right ventricular cardiomyopathy type 5. Domínguez, Fernando Zorio, Esther Jiménez Jaimez, Juan Salguero Bodes, Rafael Zwart, Robert González López, Esther Molina, Pilar Bermúdez Jiménez, Francisco Delgado, Juan F. Braza-Boïls, Aitana Bornstein, Belen Toquero, Jorge Segovia, Javier Van Tintelen, Peter Lara Pezzi, Enrique García Pavía, Pablo 2020 http://hdl.handle.net/10641/1962 https://doi.org/10.1016/j.hrthm.2020.01.035 eng eng Heart Rhythm https://www.heartrhythmjournal.com/article/S1547-5271(20)30094-1/fulltext 1547-5271 http://hdl.handle.net/10641/1962 doi:10.1016/j.hrthm.2020.01.035 Atribución-NoComercial-SinDerivadas 3.0 España http://creativecommons.org/licenses/by-nc-nd/3.0/es/ openAccess CC-BY-NC-ND Arrhythmogenic right ventricular cardiomyopathy Exercise Genetics Arrhythmia article 2020 ftunivfdv https://doi.org/10.1016/j.hrthm.2020.01.035 2021-02-10T00:31:51Z Background 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. Objective 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. Methods 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. Results 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 <50%. Compared with noncarriers, the R-wave voltage in lead V 3 was lower (3.2 ± 2.8 mV vs 7.5 ± 3.6 mV; P < .001) and QRS complex in right precordial leads wider (104.7 ± 24.0 ms vs 88.2 ± 7.7 ms; P = .001). A history of vigorous exercise showed a trend toward more ventricular arrhythmias only in women ( P = .053). Conclusion 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. pre-print 5762 KB Article in Journal/Newspaper Newfoundland Universidad Francisco de Vitoria: Depósito Digital FV (DDFV) Canada Heart Rhythm 17 6 945 954 |
institution |
Open Polar |
collection |
Universidad Francisco de Vitoria: Depósito Digital FV (DDFV) |
op_collection_id |
ftunivfdv |
language |
English |
topic |
Arrhythmogenic right ventricular cardiomyopathy Exercise Genetics Arrhythmia |
spellingShingle |
Arrhythmogenic right ventricular cardiomyopathy Exercise Genetics Arrhythmia Domínguez, Fernando Zorio, Esther Jiménez Jaimez, Juan Salguero Bodes, Rafael Zwart, Robert González López, Esther Molina, Pilar Bermúdez Jiménez, Francisco Delgado, Juan F. Braza-Boïls, Aitana Bornstein, Belen Toquero, Jorge Segovia, Javier Van Tintelen, Peter Lara Pezzi, Enrique García Pavía, Pablo Clinical characteristics and determinants of phenotype in TMEM43 Arrhythmogenic right ventricular cardiomyopathy type 5. |
topic_facet |
Arrhythmogenic right ventricular cardiomyopathy Exercise Genetics Arrhythmia |
description |
Background 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. Objective 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. Methods 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. Results 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 <50%. Compared with noncarriers, the R-wave voltage in lead V 3 was lower (3.2 ± 2.8 mV vs 7.5 ± 3.6 mV; P < .001) and QRS complex in right precordial leads wider (104.7 ± 24.0 ms vs 88.2 ± 7.7 ms; P = .001). A history of vigorous exercise showed a trend toward more ventricular arrhythmias only in women ( P = .053). Conclusion 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. pre-print 5762 KB |
format |
Article in Journal/Newspaper |
author |
Domínguez, Fernando Zorio, Esther Jiménez Jaimez, Juan Salguero Bodes, Rafael Zwart, Robert González López, Esther Molina, Pilar Bermúdez Jiménez, Francisco Delgado, Juan F. Braza-Boïls, Aitana Bornstein, Belen Toquero, Jorge Segovia, Javier Van Tintelen, Peter Lara Pezzi, Enrique García Pavía, Pablo |
author_facet |
Domínguez, Fernando Zorio, Esther Jiménez Jaimez, Juan Salguero Bodes, Rafael Zwart, Robert González López, Esther Molina, Pilar Bermúdez Jiménez, Francisco Delgado, Juan F. Braza-Boïls, Aitana Bornstein, Belen Toquero, Jorge Segovia, Javier Van Tintelen, Peter Lara Pezzi, Enrique García Pavía, Pablo |
author_sort |
Domínguez, Fernando |
title |
Clinical characteristics and determinants of phenotype in TMEM43 Arrhythmogenic right ventricular cardiomyopathy type 5. |
title_short |
Clinical characteristics and determinants of phenotype in TMEM43 Arrhythmogenic right ventricular cardiomyopathy type 5. |
title_full |
Clinical characteristics and determinants of phenotype in TMEM43 Arrhythmogenic right ventricular cardiomyopathy type 5. |
title_fullStr |
Clinical characteristics and determinants of phenotype in TMEM43 Arrhythmogenic right ventricular cardiomyopathy type 5. |
title_full_unstemmed |
Clinical characteristics and determinants of phenotype in TMEM43 Arrhythmogenic right ventricular cardiomyopathy type 5. |
title_sort |
clinical characteristics and determinants of phenotype in tmem43 arrhythmogenic right ventricular cardiomyopathy type 5. |
publisher |
Heart Rhythm |
publishDate |
2020 |
url |
http://hdl.handle.net/10641/1962 https://doi.org/10.1016/j.hrthm.2020.01.035 |
geographic |
Canada |
geographic_facet |
Canada |
genre |
Newfoundland |
genre_facet |
Newfoundland |
op_relation |
https://www.heartrhythmjournal.com/article/S1547-5271(20)30094-1/fulltext 1547-5271 http://hdl.handle.net/10641/1962 doi:10.1016/j.hrthm.2020.01.035 |
op_rights |
Atribución-NoComercial-SinDerivadas 3.0 España http://creativecommons.org/licenses/by-nc-nd/3.0/es/ openAccess |
op_rightsnorm |
CC-BY-NC-ND |
op_doi |
https://doi.org/10.1016/j.hrthm.2020.01.035 |
container_title |
Heart Rhythm |
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17 |
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6 |
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945 |
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954 |
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