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No major role for rare plectin variants in arrhythmogenic right ventricular cardiomyopathy.
Hoorntje, Edgar T; Posafalvi, Anna; Syrris, Petros; van der Velde, K Joeri; Bolling, Marieke C; Protonotarios, Alexandros; Boven, Ludolf G; Amat-Codina, Nuria; Groeneweg, Judith A; Wilde, Arthur A; Sobreira, Nara; Calkins, Hugh; Hauer, Richard N W; Jonkman, Marcel F; McKenna, William J; Elliott, Perry M; Sinke, Richard J; van den Berg, Maarten P; Chelko, Stephen P; James, Cynthia A; van Tintelen, J Peter; Judge, Daniel P; Jongbloed, Jan D H.
Afiliação
  • Hoorntje ET; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • Posafalvi A; Durrer Cardiovascular Research Center/Netherlands Heart Institute, Utrecht, the Netherlands.
  • Syrris P; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • van der Velde KJ; Centre for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, London, United Kingdom.
  • Bolling MC; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • Protonotarios A; Department of Dermatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • Boven LG; Centre for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, London, United Kingdom.
  • Amat-Codina N; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • Groeneweg JA; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America.
  • Wilde AA; Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
  • Sobreira N; Heart Centre, Department of Clinical and Experimental Cardiology, Cardiovascular Sciences, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
  • Calkins H; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia.
  • Hauer RNW; Department of Genetics, Johns Hopkins University School of Medicine, Baltimore, United States of America.
  • Jonkman MF; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America.
  • McKenna WJ; Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
  • Elliott PM; Department of Dermatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • Sinke RJ; Centre for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, London, United Kingdom.
  • van den Berg MP; Centre for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, London, United Kingdom.
  • Chelko SP; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • James CA; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • van Tintelen JP; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America.
  • Judge DP; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States of America.
  • Jongbloed JDH; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
PLoS One ; 13(8): e0203078, 2018.
Article em En | MEDLINE | ID: mdl-30161220
AIMS: Likely pathogenic/pathogenic variants in genes encoding desmosomal proteins play an important role in the pathophysiology of arrhythmogenic right ventricular cardiomyopathy (ARVC). However, for a substantial proportion of ARVC patients, the genetic substrate remains unknown. We hypothesized that plectin, a cytolinker protein encoded by the PLEC gene, could play a role in ARVC because it has been proposed to link the desmosomal protein desmoplakin to the cytoskeleton and therefore has a potential function in the desmosomal structure. METHODS: We screened PLEC in 359 ARVC patients and compared the frequency of rare coding PLEC variants (minor allele frequency [MAF] <0.001) between patients and controls. To assess the frequency of rare variants in the control population, we evaluated the rare coding variants (MAF <0.001) found in the European cohort of the Exome Aggregation Database. We further evaluated plectin localization by immunofluorescence in a subset of patients with and without a PLEC variant. RESULTS: Forty ARVC patients carried one or more rare PLEC variants (11%, 40/359). However, rare variants also seem to occur frequently in the control population (18%, 4754/26197 individuals). Nor did we find a difference in the prevalence of rare PLEC variants in ARVC patients with or without a desmosomal likely pathogenic/pathogenic variant (14% versus 8%, respectively). However, immunofluorescence analysis did show decreased plectin junctional localization in myocardial tissue from 5 ARVC patients with PLEC variants. CONCLUSIONS: Although PLEC has been hypothesized as a promising candidate gene for ARVC, our current study did not show an enrichment of rare PLEC variants in ARVC patients compared to controls and therefore does not support a major role for PLEC in this disorder. Although rare PLEC variants were associated with abnormal localization in cardiac tissue, the confluence of data does not support a role for plectin abnormalities in ARVC development.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Displasia Arritmogênica Ventricular Direita / Plectina Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Displasia Arritmogênica Ventricular Direita / Plectina Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Holanda