Desmin-p.L112Q Disturbs Filament Formation and Is a Likely-Pathogenic Variant Associated with Dilated Cardiomyopathy

Summary

DES encodes the muscle-specific intermediate filament protein desmin, which is highly relevant to the structural integrity of cardiomyocytes. Mutations in this gene cause different cardiomyopathies including dilated cardiomyopathy. Here, we functionally validate DES-p.L112Q using SW-13, H9c2 cells, and cardiomyocytes derived from induced pluripotent stem cells by confocal microscopy in combination with deconvolution analysis. These experiments reveal an aberrant cytoplasmic aggregation of mutant desmin. In conclusion, these functional analyses support the re-classification of DES-p.L112Q as a likely pathogenic variant leading to dilated cardiomyopathy.

Authors Lütkemeyer A, Voß S, Reckmann J, Groß J, Gärtner A, Gummert J, Milting H, Brodehl A
Journal Journal of cardiovascular development and disease
Publication Date 2025 Dec 20;13(1)
PubMed 41590830
PubMed Central PMC12842000
DOI 10.3390/jcdd13010003

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