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dc.contributor.authorOrtiz-Genga, Martín F
dc.contributor.authorCuenca, Sofía
dc.contributor.authorDal Ferro, Matteo
dc.contributor.authorZorio, Esther
dc.contributor.authorSalgado-Aranda, Ricardo
dc.contributor.authorCliment, Vicente
dc.contributor.authorPadron-Barthe, Laura 
dc.contributor.authorDuro-Aguado, Iria
dc.contributor.authorJiménez-Jáimez, Juan
dc.contributor.authorHidalgo-Olivares, Víctor M
dc.contributor.authorGarcía-Campo, Enrique
dc.contributor.authorLanzillo, Chiara
dc.contributor.authorSuárez-Mier, M Paz
dc.contributor.authorYonath, Hagith
dc.contributor.authorMarcos-Alonso, Sonia
dc.contributor.authorOchoa, Juan P
dc.contributor.authorSantomé, José L
dc.contributor.authorGarcía-Giustiniani, Diego
dc.contributor.authorRodríguez-Garrido, Jorge L
dc.contributor.authorDomínguez, Fernando
dc.contributor.authorMerlo, Marco
dc.contributor.authorPalomino, Julián
dc.contributor.authorPeña, María L
dc.contributor.authorTrujillo, Juan P
dc.contributor.authorMartín-Vila, Alicia
dc.contributor.authorStolfo, Davide
dc.contributor.authorMolina, Pilar
dc.contributor.authorLara-Pezzi, Enrique 
dc.contributor.authorCalvo-Iglesias, Francisco E
dc.contributor.authorNof, Eyal
dc.contributor.authorCalò, Leonardo
dc.contributor.authorBarriales-Villa, Roberto
dc.contributor.authorGimeno-Blanes, Juan R
dc.contributor.authorArad, Michael
dc.contributor.authorGarcía-Pavía, Pablo
dc.contributor.authorMonserrat, Lorenzo
dc.date.accessioned2019-07-29T11:23:10Z
dc.date.available2019-07-29T11:23:10Z
dc.date.issued2016-12
dc.identifier.citationJ Am Coll Cardiol. 2016; 68(22):2440-2451es_ES
dc.identifier.issn0735-1097es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7979
dc.description.abstractBACKGROUND: Filamin C (encoded by the FLNC gene) is essential for sarcomere attachment to the plasmatic membrane. FLNC mutations have been associated with myofibrillar myopathies, and cardiac involvement has been reported in some carriers. Accordingly, since 2012, the authors have included FLNC in the genetic screening of patients with inherited cardiomyopathies and sudden death. OBJECTIVES: The aim of this study was to demonstrate the association between truncating mutations in FLNC and the development of high-risk dilated and arrhythmogenic cardiomyopathies. METHODS: FLNC was studied using next-generation sequencing in 2,877 patients with inherited cardiovascular diseases. A characteristic phenotype was identified in probands with truncating mutations in FLNC. Clinical and genetic evaluation of 28 affected families was performed. Localization of filamin C in cardiac tissue was analyzed in patients with truncating FLNC mutations using immunohistochemistry. RESULTS: Twenty-three truncating mutations were identified in 28 probands previously diagnosed with dilated, arrhythmogenic, or restrictive cardiomyopathies. Truncating FLNC mutations were absent in patients with other phenotypes, including 1,078 patients with hypertrophic cardiomyopathy. Fifty-four mutation carriers were identified among 121 screened relatives. The phenotype consisted of left ventricular dilation (68%), systolic dysfunction (46%), and myocardial fibrosis (67%); inferolateral negative T waves and low QRS voltages on electrocardiography (33%); ventricular arrhythmias (82%); and frequent sudden cardiac death (40 cases in 21 of 28 families). Clinical skeletal myopathy was not observed. Penetrance was >97% in carriers older than 40 years. Truncating mutations in FLNC cosegregated with this phenotype with a dominant inheritance pattern (combined logarithm of the odds score: 9.5). Immunohistochemical staining of myocardial tissue showed no abnormal filamin C aggregates in patients with truncating FLNC mutations. CONCLUSIONS: Truncating mutations in FLNC caused an overlapping phenotype of dilated and left-dominant arrhythmogenic cardiomyopathies complicated by frequent premature sudden death. Prompt implantation of a cardiac defibrillator should be considered in affected patients harboring truncating mutations in FLNC.es_ES
dc.description.sponsorshipInstituto de Salud Carlos III [PI11/0699, PI14/0967, PI14/01477, RD012/0042/0029, RD012/0042/0049, RD012/0042/0066, RD12/0042/0069]; Spanish Ministry of Economy and Competitiveness [SAF2015-71863-REDT]; Plan Nacional de I+D+I; Plan Estatalde I+D+I, European Regional Development Fund; Health in Code SLes_ES
dc.language.isoenges_ES
dc.publisherElsevieres_ES
dc.relation.isversionofPostprintes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectfilamin Ces_ES
dc.subjectfilaminopathyes_ES
dc.subjectgenotypees_ES
dc.subjectprognosises_ES
dc.subjectsudden deathes_ES
dc.subjectventricular arrhythmiaes_ES
dc.subject.meshAdolescent es_ES
dc.subject.meshAdult es_ES
dc.subject.meshAged es_ES
dc.subject.meshCardiomyopathies es_ES
dc.subject.meshChild es_ES
dc.subject.meshChild, Preschool es_ES
dc.subject.meshDNA es_ES
dc.subject.meshDNA Mutational Analysis es_ES
dc.subject.meshFemale es_ES
dc.subject.meshFilamins es_ES
dc.subject.meshGenotype es_ES
dc.subject.meshHumans es_ES
dc.subject.meshImmunohistochemistry es_ES
dc.subject.meshInfant es_ES
dc.subject.meshMale es_ES
dc.subject.meshMiddle Aged es_ES
dc.subject.meshPrognosis es_ES
dc.subject.meshRetrospective Studies es_ES
dc.subject.meshRisk Factors es_ES
dc.subject.meshTachycardia, Ventricular es_ES
dc.subject.meshYoung Adult es_ES
dc.subject.meshMutation es_ES
dc.titleTruncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathieses_ES
dc.typeArtículoes_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.identifier.pubmedID27908349es_ES
dc.format.volume68es_ES
dc.format.number22es_ES
dc.format.page2440-2451es_ES
dc.identifier.doi10.1016/j.jacc.2016.09.927es_ES
dc.contributor.funderInstituto de Salud Carlos III - ISCIIIes_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)es_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1558-3597es_ES
dc.relation.publisherversionhttps://doi.org/10.1016/j.jacc.2016.09.927es_ES
dc.identifier.journalJournal of the American College of Cardiologyes_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Regulación Molecular de la Insuficiencia Cardiacaes_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2015-71863-REDTes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI11/0699es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI14/0967es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI14/01477es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD012/0042/0029es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD012/0042/0049es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD012/0042/0066es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD12/0042/0069es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
This item is licensed under a: Attribution-NonCommercial-NoDerivatives 4.0 Internacional