A Novel Truncating Variant in FLNC-Encoded Filamin C May Serve as a Proarrhythmic Genetic Substrate for Arrhythmogenic Bileaflet Mitral Valve Prolapse Syndrome

Sahej Bains, David J. Tester, Samuel J. Asirvatham, Peter A. Noseworthy, Michael J. Ackerman, John R. Giudicessi

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

A 51-year-old man with a long-standing history of bileaflet mitral valve prolapse accompanied by mitral annular disjunction and mild mitral regurgitation presented for evaluation of increasingly frequent palpitations. Ambulatory Holter monitoring, cardiac magnetic resonance imaging, serial transthoracic echocardiography, and diagnostic electrophysiology studies were consistent with a diagnosis of arrhythmogenic bileaflet mitral valve prolapse syndrome. Because of the presence of a similar phenotype in the proband's mother, brother, and maternal aunt, research-based whole exome sequencing was pursued and a novel truncating variant (p.Trp34*-FLNC) in the cardiomyopathy-causative FLNC-encoded filamin C unearthed that cosegregated with disease. Unexpectedly, these observations provide the first evidence that a heritable proarrhythmic genetic substrate (ie, FLNC haploinsufficiency–mediated weakening of cell-cell adhesion) may underlie, at least in part, some cases of arrhythmogenic mitral valve prolapse syndrome.

Original languageEnglish (US)
Pages (from-to)906-913
Number of pages8
JournalMayo Clinic proceedings
Volume94
Issue number5
DOIs
StatePublished - May 2019

ASJC Scopus subject areas

  • Medicine(all)

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