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Whole-Exome Sequencing Revealed New Candidate Genes for Human Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is a complex disease affecting young adults. It is a pathological condition impairing myocardium activity that leads to heart failure and, in the most severe cases, transplantation, which is currently the only possible therapy for the disease. DCM can be attributed to ma...

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Autores principales: D’Agostino, Ylenia, Palumbo, Domenico, Rusciano, Maria Rosaria, Strianese, Oriana, Amabile, Sonia, Di Rosa, Domenico, De Angelis, Elena, Visco, Valeria, Russo, Fabio, Alexandrova, Elena, Salvati, Annamaria, Giurato, Giorgio, Nassa, Giovanni, Tarallo, Roberta, Galasso, Gennaro, Ciccarelli, Michele, Weisz, Alessandro, Rizzo, Francesca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9600457/
https://www.ncbi.nlm.nih.gov/pubmed/36292100
http://dx.doi.org/10.3390/diagnostics12102411
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author D’Agostino, Ylenia
Palumbo, Domenico
Rusciano, Maria Rosaria
Strianese, Oriana
Amabile, Sonia
Di Rosa, Domenico
De Angelis, Elena
Visco, Valeria
Russo, Fabio
Alexandrova, Elena
Salvati, Annamaria
Giurato, Giorgio
Nassa, Giovanni
Tarallo, Roberta
Galasso, Gennaro
Ciccarelli, Michele
Weisz, Alessandro
Rizzo, Francesca
author_facet D’Agostino, Ylenia
Palumbo, Domenico
Rusciano, Maria Rosaria
Strianese, Oriana
Amabile, Sonia
Di Rosa, Domenico
De Angelis, Elena
Visco, Valeria
Russo, Fabio
Alexandrova, Elena
Salvati, Annamaria
Giurato, Giorgio
Nassa, Giovanni
Tarallo, Roberta
Galasso, Gennaro
Ciccarelli, Michele
Weisz, Alessandro
Rizzo, Francesca
author_sort D’Agostino, Ylenia
collection PubMed
description Dilated cardiomyopathy (DCM) is a complex disease affecting young adults. It is a pathological condition impairing myocardium activity that leads to heart failure and, in the most severe cases, transplantation, which is currently the only possible therapy for the disease. DCM can be attributed to many genetic determinants interacting with environmental factors, resulting in a highly variable phenotype. Due to this complexity, the early identification of causative gene mutations is an important goal to provide a genetic diagnosis, implement pre-symptomatic interventions, and predict prognosis. The advent of next-generation sequencing (NGS) has opened a new path for mutation screening, and exome sequencing provides a promising approach for identifying causal variants in known genes and novel disease-associated candidates. We analyzed the whole-exome sequencing (WES) of 15 patients affected by DCM without overloading (hypertension, valvular, or congenital heart disease) or chronic ischemic conditions. We identified 70 pathogenic or likely pathogenic variants and 1240 variants of uncertain clinical significance. Gene ontology enrichment analysis was performed to assess the potential connections between affected genes and biological or molecular function, identifying genes directly related to extracellular matrix organization, transcellular movement through the solute carrier and ATP-binding cassette transporter, and vitamin B12 metabolism. We found variants in genes implicated to a different extent in cardiac function that may represent new players in the complex genetic scenario of DCM.
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spelling pubmed-96004572022-10-27 Whole-Exome Sequencing Revealed New Candidate Genes for Human Dilated Cardiomyopathy D’Agostino, Ylenia Palumbo, Domenico Rusciano, Maria Rosaria Strianese, Oriana Amabile, Sonia Di Rosa, Domenico De Angelis, Elena Visco, Valeria Russo, Fabio Alexandrova, Elena Salvati, Annamaria Giurato, Giorgio Nassa, Giovanni Tarallo, Roberta Galasso, Gennaro Ciccarelli, Michele Weisz, Alessandro Rizzo, Francesca Diagnostics (Basel) Article Dilated cardiomyopathy (DCM) is a complex disease affecting young adults. It is a pathological condition impairing myocardium activity that leads to heart failure and, in the most severe cases, transplantation, which is currently the only possible therapy for the disease. DCM can be attributed to many genetic determinants interacting with environmental factors, resulting in a highly variable phenotype. Due to this complexity, the early identification of causative gene mutations is an important goal to provide a genetic diagnosis, implement pre-symptomatic interventions, and predict prognosis. The advent of next-generation sequencing (NGS) has opened a new path for mutation screening, and exome sequencing provides a promising approach for identifying causal variants in known genes and novel disease-associated candidates. We analyzed the whole-exome sequencing (WES) of 15 patients affected by DCM without overloading (hypertension, valvular, or congenital heart disease) or chronic ischemic conditions. We identified 70 pathogenic or likely pathogenic variants and 1240 variants of uncertain clinical significance. Gene ontology enrichment analysis was performed to assess the potential connections between affected genes and biological or molecular function, identifying genes directly related to extracellular matrix organization, transcellular movement through the solute carrier and ATP-binding cassette transporter, and vitamin B12 metabolism. We found variants in genes implicated to a different extent in cardiac function that may represent new players in the complex genetic scenario of DCM. MDPI 2022-10-05 /pmc/articles/PMC9600457/ /pubmed/36292100 http://dx.doi.org/10.3390/diagnostics12102411 Text en © 2022 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
D’Agostino, Ylenia
Palumbo, Domenico
Rusciano, Maria Rosaria
Strianese, Oriana
Amabile, Sonia
Di Rosa, Domenico
De Angelis, Elena
Visco, Valeria
Russo, Fabio
Alexandrova, Elena
Salvati, Annamaria
Giurato, Giorgio
Nassa, Giovanni
Tarallo, Roberta
Galasso, Gennaro
Ciccarelli, Michele
Weisz, Alessandro
Rizzo, Francesca
Whole-Exome Sequencing Revealed New Candidate Genes for Human Dilated Cardiomyopathy
title Whole-Exome Sequencing Revealed New Candidate Genes for Human Dilated Cardiomyopathy
title_full Whole-Exome Sequencing Revealed New Candidate Genes for Human Dilated Cardiomyopathy
title_fullStr Whole-Exome Sequencing Revealed New Candidate Genes for Human Dilated Cardiomyopathy
title_full_unstemmed Whole-Exome Sequencing Revealed New Candidate Genes for Human Dilated Cardiomyopathy
title_short Whole-Exome Sequencing Revealed New Candidate Genes for Human Dilated Cardiomyopathy
title_sort whole-exome sequencing revealed new candidate genes for human dilated cardiomyopathy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9600457/
https://www.ncbi.nlm.nih.gov/pubmed/36292100
http://dx.doi.org/10.3390/diagnostics12102411
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