Distinct molecular features of FLNC mutations, associated with different clinical phenotypes.

ABSTRACT: Filamin С is a key an actin-binding protein of muscle cells playing a critical role in maintaining structural integrity and sarcomere organization. FLNC mutations contribute to various types of cardiomyopathies and myopathies through potentially different molecular mechanisms. Here, we described the impact of two clinically distinct FLNC variants (R1267Q associated with arrhythmogenic cardiomyopathy and V2264M associated with restrictive cardiomyopathy) on calcium homeostasis, electrophysiology, and gene expression profile of iPSC-derived patient-specific cardiomyocytes. We demonstrated that R1267Q FLNC variant leads to greater disturbances in calcium dynamics, Nav1.5 kinetics and action potentials compared to V2264M variant. These functional characteristics were accompanied by transcripto

SUBMITTER: E S K 

PROVIDER: S-EPMC11904857 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature