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oai:repisalud.isciii.es:20.500.12105/103102024-09-27T09:14:11Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud author Domínguez, Fernando author Zorio, Esther author Jimenez-Jaimez, Juan author Salguero-Bodes, Rafael author Zwart, Robert author Gonzalez-Lopez, Esther author Molina, Pilar author Bermúdez-Jiménez, Francisco author Delgado, Juan F author Braza-Boïls, Aitana author Bornstein, Belen author Toquero, Jorge author Segovia, Javier author Van Tintelen, J Peter author Lara-Pezzi, Enrique author García-Pavía, Pablo funder Instituto de Salud Carlos III funder Fundación ProCNIC funder Fundación Isabel Gemio funder Sociedad Española de Cardiología funder Unión Europea. Comisión Europea funder Ministerio de Economía y Competitividad (España) funder Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) funder Ministerio de Ciencia, Innovación y Universidades (España) 2020-06-09T15:47:05Z 2020-06-09T15:47:05Z 2020-06 Heart Rhythm. 2020; 17(6):945-954 10.1016/j.hrthm.2020.01.035 1556-3871 Heart rhythm 32062046 http://hdl.handle.net/20.500.12105/10310 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 <50%. Compared with noncarriers, the R-wave voltage in lead V3 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). 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. eng Clinical characteristics and determinants of the phenotype in TMEM43 arrhythmogenic right ventricular cardiomyopathy type 5. journal article 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 URL https://repisalud.isciii.es/bitstreams/052cd35f-069f-44b2-b940-546ba55bd3da/download File MD5 36635795e22ff6024ea1640d90b601e1 962224 application/pdf ClinicalCharacteristicsDeterminantsPhenotype_2020.pdf URL https://repisalud.isciii.es/bitstreams/af64dbaf-7b40-4410-9d75-e02368931305/download File MD5 9804c13e31d73e88312044f9bf8671b3 36814 text/plain ClinicalCharacteristicsDeterminantsPhenotype_2020.pdf.txt