Genetics of Diseases of the Nuclear Envelope

Abstract Mutations inlamin A/C gene(LMNA) gene, which encodes A‐type nuclear lamins, cause a diverse range of diseases called laminopathies. These diseases selectively affect different tissues and organ systems. The main function of A‐type nuclear lamins is to provide structural scaffolding for the cell nucleus. However, the lamina also serves other functions, such as having a role in chromatin organisation, connecting the nucleus to the cytoplasm, gene transcription and mitosis. Since the first mutations inLMNAthat causes a human disease identified in 1999, the A‐type lamins get a lot of focus from the scientific community. More than a decade later, promising therapeutic approaches emerge that will hopefully lead to new ways to treat or prevent laminopathies. Key Concepts: LMNAgene encodes ubiquitously expressed nuclear A‐type lamins. LMNAmutations cause several diseases affecting specific tissues or progeroid syndrome, that is, laminopathies. Studies on mouse models ofLMNA‐dilated cardiomyopathy showed that MAP kinase and AKT/mTOR signalling are abnormally activated. Post‐translational modifications of lamin A are important for the pathogenesis of progeria. Small molecules have been successfully usedin vivoto alleviate the symptoms ofLMNA‐dilated cardiomyopathy and progeria.