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Next-Generation Sequencing Gene Panels in Inheritable Cardiomyopathies and Channelopathies: Prevalence of Pathogenic Variants and Variants of Unknown Significance in Uncommon Genes

The diffusion of next-generation sequencing (NGS)-based approaches allows for the identification of pathogenic mutations of cardiomyopathies and channelopathies in more than 200 different genes. Since genes considered uncommon for a clinical phenotype are also now included in molecular testing, the...

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Autores principales: Mazzaccara, Cristina, Lombardi, Raffaella, Mirra, Bruno, Barretta, Ferdinando, Esposito, Maria Valeria, Uomo, Fabiana, Caiazza, Martina, Monda, Emanuele, Losi, Maria Angela, Limongelli, Giuseppe, D’Argenio, Valeria, Frisso, Giulia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599286/
https://www.ncbi.nlm.nih.gov/pubmed/36291626
http://dx.doi.org/10.3390/biom12101417
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author Mazzaccara, Cristina
Lombardi, Raffaella
Mirra, Bruno
Barretta, Ferdinando
Esposito, Maria Valeria
Uomo, Fabiana
Caiazza, Martina
Monda, Emanuele
Losi, Maria Angela
Limongelli, Giuseppe
D’Argenio, Valeria
Frisso, Giulia
author_facet Mazzaccara, Cristina
Lombardi, Raffaella
Mirra, Bruno
Barretta, Ferdinando
Esposito, Maria Valeria
Uomo, Fabiana
Caiazza, Martina
Monda, Emanuele
Losi, Maria Angela
Limongelli, Giuseppe
D’Argenio, Valeria
Frisso, Giulia
author_sort Mazzaccara, Cristina
collection PubMed
description The diffusion of next-generation sequencing (NGS)-based approaches allows for the identification of pathogenic mutations of cardiomyopathies and channelopathies in more than 200 different genes. Since genes considered uncommon for a clinical phenotype are also now included in molecular testing, the detection rate of disease-causing variants has increased. Here, we report the prevalence of genetic variants detected by using a NGS custom panel in a cohort of 133 patients with inherited cardiomyopathies (n = 77) or channelopathies (n = 56). We identified 82 variants, of which 50 (61%) were identified in genes without a strong or definitive evidence of disease association according to the NIH-funded Clinical Genome Resource (ClinGen; “uncommon genes”). Among these, 35 (70%) were variants of unknown significance (VUSs), 13 (26%) were pathogenic (P) or likely pathogenic (LP) mutations, and 2 (4%) benign (B) or likely benign (LB) variants according to American College of Medical Genetics (ACMG) classifications. These data reinforce the need for the screening of uncommon genes in order to increase the diagnostic sensitivity of the genetic testing of inherited cardiomyopathies and channelopathies by allowing for the identification of mutations in genes that are not usually explored due to a currently poor association with the clinical phenotype.
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spelling pubmed-95992862022-10-27 Next-Generation Sequencing Gene Panels in Inheritable Cardiomyopathies and Channelopathies: Prevalence of Pathogenic Variants and Variants of Unknown Significance in Uncommon Genes Mazzaccara, Cristina Lombardi, Raffaella Mirra, Bruno Barretta, Ferdinando Esposito, Maria Valeria Uomo, Fabiana Caiazza, Martina Monda, Emanuele Losi, Maria Angela Limongelli, Giuseppe D’Argenio, Valeria Frisso, Giulia Biomolecules Article The diffusion of next-generation sequencing (NGS)-based approaches allows for the identification of pathogenic mutations of cardiomyopathies and channelopathies in more than 200 different genes. Since genes considered uncommon for a clinical phenotype are also now included in molecular testing, the detection rate of disease-causing variants has increased. Here, we report the prevalence of genetic variants detected by using a NGS custom panel in a cohort of 133 patients with inherited cardiomyopathies (n = 77) or channelopathies (n = 56). We identified 82 variants, of which 50 (61%) were identified in genes without a strong or definitive evidence of disease association according to the NIH-funded Clinical Genome Resource (ClinGen; “uncommon genes”). Among these, 35 (70%) were variants of unknown significance (VUSs), 13 (26%) were pathogenic (P) or likely pathogenic (LP) mutations, and 2 (4%) benign (B) or likely benign (LB) variants according to American College of Medical Genetics (ACMG) classifications. These data reinforce the need for the screening of uncommon genes in order to increase the diagnostic sensitivity of the genetic testing of inherited cardiomyopathies and channelopathies by allowing for the identification of mutations in genes that are not usually explored due to a currently poor association with the clinical phenotype. MDPI 2022-10-03 /pmc/articles/PMC9599286/ /pubmed/36291626 http://dx.doi.org/10.3390/biom12101417 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
Mazzaccara, Cristina
Lombardi, Raffaella
Mirra, Bruno
Barretta, Ferdinando
Esposito, Maria Valeria
Uomo, Fabiana
Caiazza, Martina
Monda, Emanuele
Losi, Maria Angela
Limongelli, Giuseppe
D’Argenio, Valeria
Frisso, Giulia
Next-Generation Sequencing Gene Panels in Inheritable Cardiomyopathies and Channelopathies: Prevalence of Pathogenic Variants and Variants of Unknown Significance in Uncommon Genes
title Next-Generation Sequencing Gene Panels in Inheritable Cardiomyopathies and Channelopathies: Prevalence of Pathogenic Variants and Variants of Unknown Significance in Uncommon Genes
title_full Next-Generation Sequencing Gene Panels in Inheritable Cardiomyopathies and Channelopathies: Prevalence of Pathogenic Variants and Variants of Unknown Significance in Uncommon Genes
title_fullStr Next-Generation Sequencing Gene Panels in Inheritable Cardiomyopathies and Channelopathies: Prevalence of Pathogenic Variants and Variants of Unknown Significance in Uncommon Genes
title_full_unstemmed Next-Generation Sequencing Gene Panels in Inheritable Cardiomyopathies and Channelopathies: Prevalence of Pathogenic Variants and Variants of Unknown Significance in Uncommon Genes
title_short Next-Generation Sequencing Gene Panels in Inheritable Cardiomyopathies and Channelopathies: Prevalence of Pathogenic Variants and Variants of Unknown Significance in Uncommon Genes
title_sort next-generation sequencing gene panels in inheritable cardiomyopathies and channelopathies: prevalence of pathogenic variants and variants of unknown significance in uncommon genes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599286/
https://www.ncbi.nlm.nih.gov/pubmed/36291626
http://dx.doi.org/10.3390/biom12101417
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