Reduction in Filamin C transcript is associated with arrhythmogenic cardiomyopathy in Ashkenazi Jews

Shimrit Oz*, Hagith Yonath, Leonid Visochyk, Efrat Ofek, Natalie Landa, Haike Reznik-Wolf, Martin Ortiz-Genga, Lorenzo Monserrat, Tuvia Ben-Gal, Orly Goitein, Roy Beinart, Michael Glikson, Dov Freimark, Elon Pras, Michael Arad, Eyal Nof

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Background: Filamin C is a cytoskeletal protein expressed in cardiac cells. Nonsense variations in the filamin C gene (FLNC) were associated with dilated and arrhythmogenic cardiomyopathies. Methods and results: We identified an intronic variation in FLNC gene (c.3791-1G > C) in three unrelated Ashkenazi Jewish families with variable expression of arrhythmia and cardiomyopathy. cDNA was prepared from a mutation carrier's cultured skin fibroblasts. Quantitative PCR demonstrated a reduction in total FLNC transcript, and no other FLNC splice variants were found. Single-nucleotide polymorphism (SNP) analysis revealed heterozygous variations in the genomic DNA that were not expressed in the messenger RNA. Immunohistochemical analysis of cardiac sections detected a normal distribution of filamin C protein in the heart ventricles. Conclusion: The transcript that included the FLNC variant was degraded. Haploinsufficiency in filamin C underlies arrhythmogenic cardiomyopathy with variable symptoms.

Original languageEnglish
Pages (from-to)133-138
Number of pages6
JournalInternational Journal of Cardiology
Volume317
DOIs
StatePublished - 15 Oct 2020

Funding

FundersFunder number
Dizengoff Trading Company
German-Israel Foundation for Research and Development
German-Israeli Foundation for Scientific Research and DevelopmentI-1452-203.13/2018

    Keywords

    • Arrhythmogenic cardiomyopathy
    • Filamin C
    • Gene expression and regulation

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