Skeletal and Cardiac Muscle Disorders Caused by Mutations in Genes Encoding Intermediate Filament Proteins

• Main Authors: Lorenzo Maggi, Manolis Mavroidis, Stelios Psarras, Yassemi Capetanaki, Giovanna Lattanzi
• Format: Article
• Language: English
• Published: MDPI AG 2021-04-01
• Series: International Journal of Molecular Sciences
• Subjects: desmin; lamin A/C; synemin; desminopathy; muscular laminopathies; cardiomyopathy
• Online Access: https://www.mdpi.com/1422-0067/22/8/4256

Intermediate filaments are major components of the cytoskeleton. Desmin and synemin, cytoplasmic intermediate filament proteins and A-type lamins, nuclear intermediate filament proteins, play key roles in skeletal and cardiac muscle. Desmin, encoded by the <i>DES</i> gene (OMIM *125660) and A-type lamins by the <i>LMNA</i> gene (OMIM *150330), have been involved in striated muscle disorders. Diseases include desmin-related myopathy and cardiomyopathy (desminopathy), which can be manifested with dilated, restrictive, hypertrophic, arrhythmogenic, or even left ventricular non-compaction cardiomyopathy, Emery–Dreifuss Muscular Dystrophy (EDMD2 and EDMD3, due to <i>LMNA</i> mutations), <i>LMNA</i>-related congenital Muscular Dystrophy (L-CMD) and <i>LMNA</i>-linked dilated cardiomyopathy with conduction system defects (CMD1A). Recently, mutations in synemin (<i>SYNM</i> gene, OMIM *606087) have been linked to cardiomyopathy. This review will summarize clinical and molecular aspects of desmin-, lamin- and synemin-related striated muscle disorders with focus on <i>LMNA</i> and <i>DES</i>-associated clinical entities and will suggest pathogenetic hypotheses based on the interplay of desmin and lamin A/C. In healthy muscle, such interplay is responsible for the involvement of this network in mechanosignaling, nuclear positioning and mitochondrial homeostasis, while in disease it is disturbed, leading to myocyte death and activation of inflammation and the associated secretome alterations.