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

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. We identified an intronic variation in FLNC gene (c.3791-1G > C) in three unrelated Ashkenazi Jewish families with var...

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Bibliographic Details
Published in:International journal of cardiology 2020-10, Vol.317 (C), p.133-138
Main Authors: Oz, Shimrit, Yonath, Hagith, Visochyk, Leonid, Ofek, Efrat, Landa, Natalie, Reznik-Wolf, Haike, Ortiz-Genga, Martin, Monserrat, Lorenzo, Ben-Gal, Tuvia, Goitein, Orly, Beinart, Roy, Glikson, Michael, Freimark, Dov, Pras, Elon, Arad, Michael, Nof, Eyal
Format: Article
Language:English
Subjects:
Arrhythmogenic cardiomyopathy
Cardiomyopathies
Filamin C
Filamins - genetics
Gene expression and regulation
Heterozygote
Humans
Jews
Mutation
Pedigree
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Summary: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. 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. The transcript that included the FLNC variant was degraded. Haploinsufficiency in filamin C underlies arrhythmogenic cardiomyopathy with variable symptoms. •Intronic variation in FLNC was found in three unrelated Jewish Ashkenazi families.•Variation carriers had a variable expression of arrhythmogenic cardiomyopathy.•The mutated FLNC transcript was degraded.•Filamin C was distributed normally in myocytes.
ISSN:0167-5273
1874-1754
DOI:10.1016/j.ijcard.2020.04.005