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 rela...
| Autores: | , , , , , , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2022 |
| País: | España |
| Recursos: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/23441 |
| Acesso em linha: | https://hdl.handle.net/20.500.12105/23441 |
| Access Level: | acceso abierto |
| Palavra-chave: | NGS for diagnostics of CVDs cardiomyopathies cardiomyopathy genetic genetic testing hypertrophic cardiomyopathy next-generation sequencing variant classification variant interpretation Sarcómeros Cadenas Pesadas de Miosina Cardiomiopatía Hipertrófica Muerte Súbita Humanos Miosinas Cardíacas Estudios de Asociación Genética Fenotipo Cardiac Myosins Phenotype Death, Sudden Sarcomeres Humans Cardiomyopathy, Hypertrophic Genetic Association Studies Myosin Heavy Chains |
| Resumo: | 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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