Desmin Mutations and Arrhythmogenic Right Ventricular Cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease characterized by fibrofatty replacement of the myocardium and ventricular arrhythmias, associated with mutations in the desmosomal genes. Only a missense mutation in the DES gene coding for desmin, the interm...

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Autores principales: Lorenzon, Alessandra, Beffagna, Giorgia, Bauce, Barbara, De Bortoli, Marzia, Li Mura, Ilena E.A., Calore, Martina, Dazzo, Emanuela, Basso, Cristina, Nava, Andrea, Thiene, Gaetano, Rampazzo, Alessandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Excerpta Medica 2013
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554957/
https://www.ncbi.nlm.nih.gov/pubmed/23168288
http://dx.doi.org/10.1016/j.amjcard.2012.10.017
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author Lorenzon, Alessandra
Beffagna, Giorgia
Bauce, Barbara
De Bortoli, Marzia
Li Mura, Ilena E.A.
Calore, Martina
Dazzo, Emanuela
Basso, Cristina
Nava, Andrea
Thiene, Gaetano
Rampazzo, Alessandra
author_facet Lorenzon, Alessandra
Beffagna, Giorgia
Bauce, Barbara
De Bortoli, Marzia
Li Mura, Ilena E.A.
Calore, Martina
Dazzo, Emanuela
Basso, Cristina
Nava, Andrea
Thiene, Gaetano
Rampazzo, Alessandra
author_sort Lorenzon, Alessandra
collection PubMed
description Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease characterized by fibrofatty replacement of the myocardium and ventricular arrhythmias, associated with mutations in the desmosomal genes. Only a missense mutation in the DES gene coding for desmin, the intermediate filament protein expressed by cardiac and skeletal muscle cells, has been recently associated with ARVC. We screened 91 ARVC index cases (53 negative for mutations in desmosomal genes and an additional 38 carrying desmosomal gene mutations) for DES mutations. Two rare missense variants were identified. The heterozygous p.K241E substitution was detected in 1 patient affected with a severe form of ARVC who also carried the p.T816RfsX10 mutation in plakophilin-2 gene. This DES substitution, showing an allele frequency of <0.01 in the control population, is predicted to cause an intolerant amino acid change in a highly conserved protein domain. Thus, it can be considered a rare variant with a possible modifier effect on the phenotypic expression of the concomitant mutation. The previously known p.A213V substitution was identified in 1 patient with ARVC who was negative for mutations in the desmosomal genes. Because a greater prevalence of p.A213V has been reported in patients with heart dilation than in control subjects, the hypothesis that this rare variant could have an unfavorable effect on cardiac remodeling cannot be ruled out. In conclusion, our data help to establish that, in the absence of skeletal muscle involvement suggestive of a desminopathy, the probability of DES mutations in ARVC is very low. These findings have important implications in the mutation screening strategy for patients with ARVC.
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spelling pubmed-35549572013-02-01 Desmin Mutations and Arrhythmogenic Right Ventricular Cardiomyopathy Lorenzon, Alessandra Beffagna, Giorgia Bauce, Barbara De Bortoli, Marzia Li Mura, Ilena E.A. Calore, Martina Dazzo, Emanuela Basso, Cristina Nava, Andrea Thiene, Gaetano Rampazzo, Alessandra Am J Cardiol Cardiomyopathy Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease characterized by fibrofatty replacement of the myocardium and ventricular arrhythmias, associated with mutations in the desmosomal genes. Only a missense mutation in the DES gene coding for desmin, the intermediate filament protein expressed by cardiac and skeletal muscle cells, has been recently associated with ARVC. We screened 91 ARVC index cases (53 negative for mutations in desmosomal genes and an additional 38 carrying desmosomal gene mutations) for DES mutations. Two rare missense variants were identified. The heterozygous p.K241E substitution was detected in 1 patient affected with a severe form of ARVC who also carried the p.T816RfsX10 mutation in plakophilin-2 gene. This DES substitution, showing an allele frequency of <0.01 in the control population, is predicted to cause an intolerant amino acid change in a highly conserved protein domain. Thus, it can be considered a rare variant with a possible modifier effect on the phenotypic expression of the concomitant mutation. The previously known p.A213V substitution was identified in 1 patient with ARVC who was negative for mutations in the desmosomal genes. Because a greater prevalence of p.A213V has been reported in patients with heart dilation than in control subjects, the hypothesis that this rare variant could have an unfavorable effect on cardiac remodeling cannot be ruled out. In conclusion, our data help to establish that, in the absence of skeletal muscle involvement suggestive of a desminopathy, the probability of DES mutations in ARVC is very low. These findings have important implications in the mutation screening strategy for patients with ARVC. Excerpta Medica 2013-02-01 /pmc/articles/PMC3554957/ /pubmed/23168288 http://dx.doi.org/10.1016/j.amjcard.2012.10.017 Text en © 2013 Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/3.0/ Open Access under CC BY-NC-ND 3.0 (https://creativecommons.org/licenses/by-nc-nd/3.0/) license
spellingShingle Cardiomyopathy
Lorenzon, Alessandra
Beffagna, Giorgia
Bauce, Barbara
De Bortoli, Marzia
Li Mura, Ilena E.A.
Calore, Martina
Dazzo, Emanuela
Basso, Cristina
Nava, Andrea
Thiene, Gaetano
Rampazzo, Alessandra
Desmin Mutations and Arrhythmogenic Right Ventricular Cardiomyopathy
title Desmin Mutations and Arrhythmogenic Right Ventricular Cardiomyopathy
title_full Desmin Mutations and Arrhythmogenic Right Ventricular Cardiomyopathy
title_fullStr Desmin Mutations and Arrhythmogenic Right Ventricular Cardiomyopathy
title_full_unstemmed Desmin Mutations and Arrhythmogenic Right Ventricular Cardiomyopathy
title_short Desmin Mutations and Arrhythmogenic Right Ventricular Cardiomyopathy
title_sort desmin mutations and arrhythmogenic right ventricular cardiomyopathy
topic Cardiomyopathy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554957/
https://www.ncbi.nlm.nih.gov/pubmed/23168288
http://dx.doi.org/10.1016/j.amjcard.2012.10.017
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