Integrated phenotypic and transcriptomic characterization of desmin-related cardiomyopathy in hiPSC-derived cardiomyocytes and machine learning-based classification of disease features.

Desmin-related diseases are characterized by skeletal muscle weakness, cardiomyopathy, and respiratory dysfunction due to mutations in the desmin gene (DES), which encodes a protein essential for muscle cell integrity. This study investigates the effects of a pathogenic desmin mutation (DES) in human cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) obtained from a patient carrying the DES mutation, compared to cardiomyocytes derived from hiPSCs of three healthy donors. To further validate our findings a genome edited cell line has been obtained following the insertion of the mutation in a control hiPSC line.