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

doi:10.1016/j.ijcard.2020.04.005

International Journal of Cardiology

Volume 317, 15 October 2020, Pages 133-138

https://doi.org/10.1016/j.ijcard.2020.04.005 Get rights and content

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Highlights

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Intronic variation in FLNC was found in three unrelated Jewish Ashkenazi families.
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Variation carriers had a variable expression of arrhythmogenic cardiomyopathy.
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The mutated FLNC transcript was degraded.
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Filamin C was distributed normally in myocytes.

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.

Keywords

Filamin C

Arrhythmogenic cardiomyopathy

Gene expression and regulation

Cited by (0)

¹: This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

²: Current address: Jesselson Heart Center, Shaare Zedek Medical Center, Jerusalem, Israel.

³: These authors contributed equally to this work.