The DES -p.A120P mutation associated with biventricular arrhythmogenic cardiomyopathy has a dominant-negative effect on desmin filament assembly

Abstract Desmin is a muscle-specific intermediate filament protein, which connects different cell organelles and is highly relevant for the structural integrity of cardiomyocytes. Mutations in the DES gene, cause different cardiomyopathies including arrhythmogenic cardiomyopathy. In this study, we functionally investigate the novel genetic variant DES -p.A120P using cell transfection experiments including cardiomyocytes derived from induced pluripotent stem cells in combination with confocal microscopy. These experiments reveal that the filament assembly of desmin-p.A120P is disturbed – even when co-expressed with wild-type desmin. In conclusion, the functional characterization of desmin-p.A120P supports the classification as a pathogenic variant associated with arrhythmogenic cardiomyopathy.