Publication

No major role for rare plectin variants in arrhythmogenic right ventricular cardiomyopathy

Hoorntje, E. T., Posafalvi, A., Syrris, P., van der Velde, K. J., Bolling, M. C., Protonotarios, A., Boven, L. G., Amat-Codina, N., Groeneweg, J. A., Wilde, A. A., Sobreira, N., Calkins, H., Hauer, R. N. W., Jonkman, M. F., McKenna, W. J., Elliott, P. M., Sinke, R. J., van den Berg, M. P., Chelko, S. P., James, C. A., van Tintelen, J. P., Judge, D. P. & Jongbloed, J. D. H., 30-Aug-2018, In : PLoS ONE. 13, 8, 14 p., e0203078.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Hoorntje, E. T., Posafalvi, A., Syrris, P., van der Velde, K. J., Bolling, M. C., Protonotarios, A., ... Jongbloed, J. D. H. (2018). No major role for rare plectin variants in arrhythmogenic right ventricular cardiomyopathy. PLoS ONE, 13(8), [e0203078]. https://doi.org/10.1371/journal.pone.0203078

Author

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. / No major role for rare plectin variants in arrhythmogenic right ventricular cardiomyopathy. In: PLoS ONE. 2018 ; Vol. 13, No. 8.

Harvard

Hoorntje, ET, Posafalvi, A, Syrris, P, van der Velde, KJ, Bolling, MC, Protonotarios, A, Boven, LG, Amat-Codina, N, Groeneweg, JA, Wilde, AA, Sobreira, N, Calkins, H, Hauer, RNW, Jonkman, MF, McKenna, WJ, Elliott, PM, Sinke, RJ, van den Berg, MP, Chelko, SP, James, CA, van Tintelen, JP, Judge, DP & Jongbloed, JDH 2018, 'No major role for rare plectin variants in arrhythmogenic right ventricular cardiomyopathy' PLoS ONE, vol. 13, no. 8, e0203078. https://doi.org/10.1371/journal.pone.0203078

Standard

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.

In: PLoS ONE, Vol. 13, No. 8, e0203078, 30.08.2018.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Hoorntje ET, Posafalvi A, Syrris P, van der Velde KJ, Bolling MC, Protonotarios A et al. No major role for rare plectin variants in arrhythmogenic right ventricular cardiomyopathy. PLoS ONE. 2018 Aug 30;13(8). e0203078. https://doi.org/10.1371/journal.pone.0203078


BibTeX

@article{585ac0b692de4d2b83a51ad8602fcb71,
title = "No major role for rare plectin variants in arrhythmogenic right ventricular cardiomyopathy",
abstract = "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.",
author = "Hoorntje, {Edgar T} and Anna Posafalvi and Petros Syrris and {van der Velde}, {K Joeri} and Bolling, {Marieke C} and Alexandros Protonotarios and Boven, {Ludolf G} and Nuria Amat-Codina and Groeneweg, {Judith A} and Wilde, {Arthur A} and Nara Sobreira and Hugh Calkins and Hauer, {Richard N W} and Jonkman, {Marcel F} and McKenna, {William J} and Elliott, {Perry M} and Sinke, {Richard J} and {van den Berg}, {Maarten P} and Chelko, {Stephen P} and James, {Cynthia A} and {van Tintelen}, {J Peter} and Judge, {Daniel P} and Jongbloed, {Jan D H}",
year = "2018",
month = "8",
day = "30",
doi = "10.1371/journal.pone.0203078",
language = "English",
volume = "13",
journal = "PLOS-One",
issn = "1932-6203",
publisher = "PUBLIC LIBRARY SCIENCE",
number = "8",

}

RIS

TY - JOUR

T1 - No major role for rare plectin variants in arrhythmogenic right ventricular cardiomyopathy

AU - Hoorntje, Edgar T

AU - Posafalvi, Anna

AU - Syrris, Petros

AU - van der Velde, K Joeri

AU - Bolling, Marieke C

AU - Protonotarios, Alexandros

AU - Boven, Ludolf G

AU - Amat-Codina, Nuria

AU - Groeneweg, Judith A

AU - Wilde, Arthur A

AU - Sobreira, Nara

AU - Calkins, Hugh

AU - Hauer, Richard N W

AU - Jonkman, Marcel F

AU - McKenna, William J

AU - Elliott, Perry M

AU - Sinke, Richard J

AU - van den Berg, Maarten P

AU - Chelko, Stephen P

AU - James, Cynthia A

AU - van Tintelen, J Peter

AU - Judge, Daniel P

AU - Jongbloed, Jan D H

PY - 2018/8/30

Y1 - 2018/8/30

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0203078

DO - 10.1371/journal.pone.0203078

M3 - Article

VL - 13

JO - PLOS-One

JF - PLOS-One

SN - 1932-6203

IS - 8

M1 - e0203078

ER -

ID: 65016357