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Variants in MHY7 Gene Cause Arrhythmogenic Cardiomyopathy

Background: Arrhythmogenic Cardiomyopathy (ACM) is a disease of the cardiac muscle, characterized by frequent ventricular arrhythmias and functional/ structural abnormalities, mainly of the right ventricle. To date, 20 different genes have been associated with ACM and the majority of them encode for...

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Autores principales: Ferradini, Valentina, Parca, Luca, Martino, Annamaria, Lanzillo, Chiara, Silvetti, Elisa, Calò, Leonardo, Caselli, Stefano, Novelli, Giuseppe, Helmer-Citterich, Manuela, Sangiuolo, Federica Carla, Mango, Ruggiero
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224781/
https://www.ncbi.nlm.nih.gov/pubmed/34067482
http://dx.doi.org/10.3390/genes12060793
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author Ferradini, Valentina
Parca, Luca
Martino, Annamaria
Lanzillo, Chiara
Silvetti, Elisa
Calò, Leonardo
Caselli, Stefano
Novelli, Giuseppe
Helmer-Citterich, Manuela
Sangiuolo, Federica Carla
Mango, Ruggiero
author_facet Ferradini, Valentina
Parca, Luca
Martino, Annamaria
Lanzillo, Chiara
Silvetti, Elisa
Calò, Leonardo
Caselli, Stefano
Novelli, Giuseppe
Helmer-Citterich, Manuela
Sangiuolo, Federica Carla
Mango, Ruggiero
author_sort Ferradini, Valentina
collection PubMed
description Background: Arrhythmogenic Cardiomyopathy (ACM) is a disease of the cardiac muscle, characterized by frequent ventricular arrhythmias and functional/ structural abnormalities, mainly of the right ventricle. To date, 20 different genes have been associated with ACM and the majority of them encode for desmosomal proteins. In this study, we describe the characterization of two novel variants in MHY7 gene, segregating in two ACM families. MYH7 encodes for myosin heavy chain β (MHC-β) isoform, involved in cardiac muscle contractility. Method and Results: In family A, the autopsy revealed ACM with biventricular involvement in both the proband and his father. In family B, the proband had been diagnosed as affected by ACM and implanted with implantable cardioverter defibrillator (ICD), due to ECG evidence of monomorphic ventricular tachycardia after syncope. After clinical evaluation, a molecular diagnosis was performed using a NGS custom panel. The two novel variants identified predicted damaging, located in a highly conserved domain: c. 2630T>C is not described while c.2609G>A has a frequency of 0.00000398. In silico analyses evaluated the docking characteristics between proteins using the Haddock2.2 webserver. Conclusions: Our results reveal two variants in sarcomeric genes to be the molecular cause of ACM, further increasing the genetic heterogeneity of the disease; in fact, sarcomeric variants are usually associated with HCM phenotype. Studies on the role of sarcomere genes in the pathogenesis of ACM are surely recommended in those ACM patients negative for desmosomal mutation screening.
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spelling pubmed-82247812021-06-25 Variants in MHY7 Gene Cause Arrhythmogenic Cardiomyopathy Ferradini, Valentina Parca, Luca Martino, Annamaria Lanzillo, Chiara Silvetti, Elisa Calò, Leonardo Caselli, Stefano Novelli, Giuseppe Helmer-Citterich, Manuela Sangiuolo, Federica Carla Mango, Ruggiero Genes (Basel) Article Background: Arrhythmogenic Cardiomyopathy (ACM) is a disease of the cardiac muscle, characterized by frequent ventricular arrhythmias and functional/ structural abnormalities, mainly of the right ventricle. To date, 20 different genes have been associated with ACM and the majority of them encode for desmosomal proteins. In this study, we describe the characterization of two novel variants in MHY7 gene, segregating in two ACM families. MYH7 encodes for myosin heavy chain β (MHC-β) isoform, involved in cardiac muscle contractility. Method and Results: In family A, the autopsy revealed ACM with biventricular involvement in both the proband and his father. In family B, the proband had been diagnosed as affected by ACM and implanted with implantable cardioverter defibrillator (ICD), due to ECG evidence of monomorphic ventricular tachycardia after syncope. After clinical evaluation, a molecular diagnosis was performed using a NGS custom panel. The two novel variants identified predicted damaging, located in a highly conserved domain: c. 2630T>C is not described while c.2609G>A has a frequency of 0.00000398. In silico analyses evaluated the docking characteristics between proteins using the Haddock2.2 webserver. Conclusions: Our results reveal two variants in sarcomeric genes to be the molecular cause of ACM, further increasing the genetic heterogeneity of the disease; in fact, sarcomeric variants are usually associated with HCM phenotype. Studies on the role of sarcomere genes in the pathogenesis of ACM are surely recommended in those ACM patients negative for desmosomal mutation screening. MDPI 2021-05-22 /pmc/articles/PMC8224781/ /pubmed/34067482 http://dx.doi.org/10.3390/genes12060793 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ferradini, Valentina
Parca, Luca
Martino, Annamaria
Lanzillo, Chiara
Silvetti, Elisa
Calò, Leonardo
Caselli, Stefano
Novelli, Giuseppe
Helmer-Citterich, Manuela
Sangiuolo, Federica Carla
Mango, Ruggiero
Variants in MHY7 Gene Cause Arrhythmogenic Cardiomyopathy
title Variants in MHY7 Gene Cause Arrhythmogenic Cardiomyopathy
title_full Variants in MHY7 Gene Cause Arrhythmogenic Cardiomyopathy
title_fullStr Variants in MHY7 Gene Cause Arrhythmogenic Cardiomyopathy
title_full_unstemmed Variants in MHY7 Gene Cause Arrhythmogenic Cardiomyopathy
title_short Variants in MHY7 Gene Cause Arrhythmogenic Cardiomyopathy
title_sort variants in mhy7 gene cause arrhythmogenic cardiomyopathy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224781/
https://www.ncbi.nlm.nih.gov/pubmed/34067482
http://dx.doi.org/10.3390/genes12060793
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