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Clinical data from six patients with LMNA mutation\u2010related lipodystrophy are analyzed, and four distinct LMNA mutations are identified. Associations between mutations and lipodystrophy phenotypes are assessed. Three LMNA mutation plasmids are constructed and transfected into HEK293 cells. Protein stability, degradation pathways, and binding proteins of mutant Lamin A\/C are examined using Western blotting, co\u2010immunoprecipitation, and mass spectrometry. Confocal microscopy is employed to observe nuclear structure. Four different LMNA mutations are identified in the six patients, all exhibiting lipodystrophy and metabolic disorders. Cardiac dysfunction is observed in two out of six patients. Metformin and pioglitazone are the primary treatments for glucose control. Confocal microscopy revealed nuclear blebbing and irregular cell membranes. Mutant Lamin A\/C stability is significantly decreased, and degradation occurred primarily via the ubiquitin\u2010proteasome system (UPS). Potential binding ubiquitination\u2010related proteins of mutant Lamin A\/C are identified. This study investigated LMNA mutation\u2010related lipodystrophy, identifying four unique mutations and their connections to specific phenotypes. It is found to decreased mutant Lamin A\/C stability and degradation primarily through the UPS, offering new insights into molecular mechanisms and potential therapeutic targets.<\/jats:p>","DOI":"10.1002\/adbi.202200301","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T01:21:37Z","timestamp":1686532897000},"source":"Crossref","is-referenced-by-count":4,"title":["The Clinical Characteristics and Potential Molecular Mechanism of LMNA Mutation\u2010Related Lipodystrophy"],"prefix":"10.1002","volume":"7","author":[{"given":"Cheng","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Endocrinology Key Laboratory of Endocrinology National Health Commission Peking Union Medical College Hospital Peking Union Medical College Chinese Academy of Medical Sciences  Beijing 100730 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of 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