NAGIOS: RODERIC FUNCIONANDO

Filamin C variants are associated with a distinctive clinical and immunohistochemical arrhythmogenic cardiomyopathy phenotype

Repositori DSpace/Manakin

IMPORTANT: Aquest repositori està en una versió antiga des del 3/12/2023. La nova instal.lació está en https://roderic.uv.es/

Filamin C variants are associated with a distinctive clinical and immunohistochemical arrhythmogenic cardiomyopathy phenotype

dc.contributor.author	Hall, Charlotte L.
dc.contributor.author	Akhtar, Mohammed M.
dc.contributor.author	Sabater-Molina, Maria
dc.contributor.author	Futema, Marta
dc.contributor.author	Asimaki, Angeliki
dc.contributor.author	Protonotarios, Alexandros
dc.contributor.author	Dalageorgou, Chrysoula
dc.contributor.author	Pittman, Alan M.
dc.contributor.author	Suarez, Mari Paz
dc.contributor.author	Aguilera, Beatriz
dc.contributor.author	Molina Aguilar, Pilar
dc.contributor.author	Zorio Grima, Esther
dc.contributor.author	Hernández, Juan Pedro
dc.contributor.author	Pastor, Francisco
dc.contributor.author	Gimeno, Juan R.
dc.contributor.author	Syrris, Petros
dc.contributor.author	McKenna, William J.
dc.date.accessioned	2021-04-19T07:40:46Z
dc.date.available	2021-04-19T07:40:46Z
dc.date.issued	2020
dc.identifier.citation	Hall, Charlotte L. Akhtar, Mohammed M. Sabater-Molina, Maria Futema, Marta Asimaki, Angeliki Protonotarios, Alexandros Dalageorgou, Chrysoula Pittman, Alan M. Suarez, Mari Paz Aguilera, Beatriz Molina Aguilar, Pilar Zorio Grima, Esther Hernández, Juan Pedro Pastor, Francisco Gimeno, Juan R. Syrris, Petros McKenna, William J. 2020 Filamin C variants are associated with a distinctive clinical and immunohistochemical arrhythmogenic cardiomyopathy phenotype International Journal of Cardiology
dc.identifier.uri	https://hdl.handle.net/10550/78750
dc.description.abstract	Background: Pathogenic variants in the filamin C (FLNC) gene are associated with inherited cardiomyopathies including dilated cardiomyopathy with an arrhythmogenic phenotype. We evaluated FLNC variants in arrhythmogenic cardiomyopathy (ACM) and investigated the disease mechanism at a molecular level. Methods: 120 gene-elusive ACM patients who fulfilled diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) were screened by whole exome sequencing. Fixed cardiac tissue from FLNC variant carriers who had died suddenly was investigated by histology and immunohistochemistry. Results: Novel or rare FLNC variants, four null and five variants of unknown significance, were identified in nine ACM probands (7.5%). In FLNC null variant carriers (including family members, n = 16) Task Force diagnostic electrocardiogram repolarization/depolarization abnormalities were uncommon (19%), echocardiography was normal in 69%, while 56% had >500 ventricular ectopics/24 h or ventricular tachycardia on Holter and 67% had late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMRI). Ten gene positive individuals (63%) had abnormalities on ECG or CMRI that are not included in the current diagnostic criteria for ARVC. Immunohistochemistry showed altered key protein distribution, distinctive from that observed in ARVC, predominantly in the left ventricle. Conclusions: ACM associated with FLNC variants presents with a distinctive phenotype characterized by Holter arrhythmia and LGE on CMRI with unremarkable ECG and echocardiographic findings. Clinical presentation in asymptomatic mutation carriers at risk of sudden death may include abnormalities which are currently non-diagnostic for ARVC. At the molecular level, the pathogenic mechanism related to FLNC appears different to classic forms of ARVC caused by desmosomal mutations. Keywords: ARVC; Arrhythmogenic cardiomyopathy; Filamin C variants; Immunohistochemistry; Late gadolinium enhancement.
dc.language.iso	eng
dc.relation.ispartof	International Journal of Cardiology, 2020
dc.subject	Patologia
dc.subject	Cor
dc.title	Filamin C variants are associated with a distinctive clinical and immunohistochemical arrhythmogenic cardiomyopathy phenotype
dc.type	journal article	es_ES
dc.date.updated	2021-04-19T07:40:47Z
dc.identifier.idgrec	145249
dc.rights.accessRights	open access	es_ES