Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Apr 15:401:131849.
doi: 10.1016/j.ijcard.2024.131849. Epub 2024 Feb 13.

Variable clinical expression of a novel FLNC truncating variant in a large family

Orr Tomer  1 , Smadar Horowitz-Cederboim  2 , Dini Rivkin  3 , Vardiella Meiner  4 , Michael H Gollob  5 , Donna R Zwas  2 , Ronen Durst  2 , Ayelet Shauer  2
Affiliations

Variable clinical expression of a novel FLNC truncating variant in a large family

Orr Tomer et al. Int J Cardiol. .

Abstract

Background: Variants in Filamin-C (FLNC) have been associated with various hereditary cardiomyopathies. Recent literature reports a prevalence of sudden cardiac death (SCD) of 13-25% among carriers of truncating-variants, with mean age of 42±15 years for first SCD event. This study reports two familial cases of SCD and the results of cascade screening of their large family.

Methods: Molecular-autopsy of the SCD victims revealed a novel truncating-variant in the FLNC gene (chr 7:128496880 [hg19]; NM_001458.5; c.7467_7474del; p.(Ser2490fs)). We screened thirty-two family members following genetic counseling, and variant carriers underwent a comprehensive workup followed by consultation with a cardiologist with expertise in the genetics of cardiac diseases.

Results: Seventeen variant carriers were identified: ages between 9 and 85 (mean 47±26). Fifteen underwent clinical evaluation. To date, none of the identified carriers has had major adverse events. In evaluated patients, ECG showed right-axis deviation in 60% (n = 9). Holter recorded frequent premature ventricular contractions (PVCs) (991±2030 per 24 h) in 33% (n = 5) with 4 patients having polymorphic PVC morphology. Three carriers had echocardiographic evidence of mild left-ventricular (LV) systolic dysfunction and another with mild LV dilatation. Cardiac magnetic-resonance (CMR) exhibited late‑gadolinium-enhancement in 10 out of 11 exams, mainly in the mid-myocardium and sub-epicardium, frequently involving the septum and the inferior-lateral wall.

Conclusion: This large FLNC truncating variant carrier family exhibits high cardiomyopathy penetrance, best diagnosed by CMR, with variable clinical expressions. These findings present a challenge in SCD prevention management and underscoring the imperative for better risk stratification measures.

Keywords: Arrhythmogenic cardiomyopathy; FLNC; Filamin-C; Sudden cardiac death; Truncating variant.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest The authors have no conflicts to disclose.

Similar articles

See all similar articles

Cited by

LinkOut - more resources