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Genotype-Phenotype Correlation in Hypertrophic Cardiomyopathy: New Variant p.Arg652Lys in MYH7

Hypertrophic cardiomyopathy (HCM) is a genetic disease characterised by increased left ventricle (LV) wall thickness caused by mutations in sarcomeric genes. Finding a causal mutation can help to better assess the proband’s risk, as it allows the presence of the mutation to be evaluated in relatives...

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Autores principales: Antoniutti, Guido, Caimi-Martinez, Fiama Giuliana, Álvarez-Rubio, Jorge, Morlanes-Gracia, Paula, Pons-Llinares, Jaume, Rodríguez-Picón, Blanca, Fortuny-Frau, Elena, Torres-Juan, Laura, Heine-Suner, Damian, Ripoll-Vera, Tomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8872101/
https://www.ncbi.nlm.nih.gov/pubmed/35205365
http://dx.doi.org/10.3390/genes13020320
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author Antoniutti, Guido
Caimi-Martinez, Fiama Giuliana
Álvarez-Rubio, Jorge
Morlanes-Gracia, Paula
Pons-Llinares, Jaume
Rodríguez-Picón, Blanca
Fortuny-Frau, Elena
Torres-Juan, Laura
Heine-Suner, Damian
Ripoll-Vera, Tomas
author_facet Antoniutti, Guido
Caimi-Martinez, Fiama Giuliana
Álvarez-Rubio, Jorge
Morlanes-Gracia, Paula
Pons-Llinares, Jaume
Rodríguez-Picón, Blanca
Fortuny-Frau, Elena
Torres-Juan, Laura
Heine-Suner, Damian
Ripoll-Vera, Tomas
author_sort Antoniutti, Guido
collection PubMed
description Hypertrophic cardiomyopathy (HCM) is a genetic disease characterised by increased left ventricle (LV) wall thickness caused by mutations in sarcomeric genes. Finding a causal mutation can help to better assess the proband’s risk, as it allows the presence of the mutation to be evaluated in relatives and the follow-up to be focused on carriers. We performed an observational study of patients with HCM due to the novel p.Arg652Lys variant in the MYH7 gene. Eight families and 59 patients are described in the follow-up for a median of 63 months, among whom 39 (66%) carry the variant. Twenty-five (64%) of carriers developed HCM. A median maximum LV wall thickness of 16.5 mm was described. The LV hypertrophy was asymmetric septal in 75% of cases, with LV outflow tract obstruction in 28%. The incidence of a composite of serious adverse cardiovascular events (sudden death, aborted sudden death, appropriate implantable cardiac defibrillator discharge, an embolic event, or admission for heart failure) was observed in five (20%) patients. Given the finding of the p.Arg652Lys variant in patients with HCM, but not in controls, with evident segregation in patients with HCM from eight families and the location in an active site of the protein, we can define this variant as likely pathogenic and associated with the development of HCM.
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spelling pubmed-88721012022-02-25 Genotype-Phenotype Correlation in Hypertrophic Cardiomyopathy: New Variant p.Arg652Lys in MYH7 Antoniutti, Guido Caimi-Martinez, Fiama Giuliana Álvarez-Rubio, Jorge Morlanes-Gracia, Paula Pons-Llinares, Jaume Rodríguez-Picón, Blanca Fortuny-Frau, Elena Torres-Juan, Laura Heine-Suner, Damian Ripoll-Vera, Tomas Genes (Basel) Article Hypertrophic cardiomyopathy (HCM) is a genetic disease characterised by increased left ventricle (LV) wall thickness caused by mutations in sarcomeric genes. Finding a causal mutation can help to better assess the proband’s risk, as it allows the presence of the mutation to be evaluated in relatives and the follow-up to be focused on carriers. We performed an observational study of patients with HCM due to the novel p.Arg652Lys variant in the MYH7 gene. Eight families and 59 patients are described in the follow-up for a median of 63 months, among whom 39 (66%) carry the variant. Twenty-five (64%) of carriers developed HCM. A median maximum LV wall thickness of 16.5 mm was described. The LV hypertrophy was asymmetric septal in 75% of cases, with LV outflow tract obstruction in 28%. The incidence of a composite of serious adverse cardiovascular events (sudden death, aborted sudden death, appropriate implantable cardiac defibrillator discharge, an embolic event, or admission for heart failure) was observed in five (20%) patients. Given the finding of the p.Arg652Lys variant in patients with HCM, but not in controls, with evident segregation in patients with HCM from eight families and the location in an active site of the protein, we can define this variant as likely pathogenic and associated with the development of HCM. MDPI 2022-02-09 /pmc/articles/PMC8872101/ /pubmed/35205365 http://dx.doi.org/10.3390/genes13020320 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
Antoniutti, Guido
Caimi-Martinez, Fiama Giuliana
Álvarez-Rubio, Jorge
Morlanes-Gracia, Paula
Pons-Llinares, Jaume
Rodríguez-Picón, Blanca
Fortuny-Frau, Elena
Torres-Juan, Laura
Heine-Suner, Damian
Ripoll-Vera, Tomas
Genotype-Phenotype Correlation in Hypertrophic Cardiomyopathy: New Variant p.Arg652Lys in MYH7
title Genotype-Phenotype Correlation in Hypertrophic Cardiomyopathy: New Variant p.Arg652Lys in MYH7
title_full Genotype-Phenotype Correlation in Hypertrophic Cardiomyopathy: New Variant p.Arg652Lys in MYH7
title_fullStr Genotype-Phenotype Correlation in Hypertrophic Cardiomyopathy: New Variant p.Arg652Lys in MYH7
title_full_unstemmed Genotype-Phenotype Correlation in Hypertrophic Cardiomyopathy: New Variant p.Arg652Lys in MYH7
title_short Genotype-Phenotype Correlation in Hypertrophic Cardiomyopathy: New Variant p.Arg652Lys in MYH7
title_sort genotype-phenotype correlation in hypertrophic cardiomyopathy: new variant p.arg652lys in myh7
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8872101/
https://www.ncbi.nlm.nih.gov/pubmed/35205365
http://dx.doi.org/10.3390/genes13020320
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