Genotype-phenotype analysis of LMNA-related diseases predicts phenotype-selective alterations in lamin phosphorylation.

ABSTRACT: Laminopathies are rare diseases associated with mutations in LMNA, which encodes nuclear lamin A/C. LMNA variants lead to diverse tissue-specific phenotypes including cardiomyopathy, lipodystrophy, myopathy, neuropathy, progeria, bone/skin disorders, and overlap syndromes. The mechanisms underlying these heterogeneous phenotypes remain poorly understood, although post-translational modifications, including phosphorylation, are postulated as regulators of lamin function. We catalogued all known lamin A/C human mutations and their associated phenotypes, and systematically examined the putative role of phosphorylation in laminopathies. In silico prediction of specific LMNA mutant-driven changes to lamin A phosphorylation and protein structure was performed using machine learning methods. Some

SUBMITTER: Lin EW 

PROVIDER: S-EPMC8059629 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature