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Open AccessArticle

Looking at New Unexpected Disease Targets in LMNA-Linked Lipodystrophies in the Light of Complex Cardiovascular Phenotypes: Implications for Clinical Practice

Inserm UMRS938, Saint-Antoine Research Center, Sorbonne University, 75012 Paris, France
Reference Center of Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), Department of Endocrinology, AP-HP Saint-Antoine Hospital, 75012 Paris, France
National Institute of Health and Medical Research, Department of Cardiology, AP-HP Saint-Antoine Hospital, 75012 Paris, France
Department of Molecular Biology and Genetics, AP-HP Saint-Antoine Hospital, 75012 Paris, France
Inserm U1190—EGID (European Genomic Institute for Diabetes), Endocrinology, Diabetology and Metabolism Department, CHU Lille, 59000 Lille, France
Reference Center of Neuromuscular Rare Diseases, CHU Fort de France, Pierre Zobda Quitman Hospital, 97200 Martinique, France
Cardiology Department, CHU Fort de France, Pierre Zobda Quitman Hospital, 97200 Martinique, France
Inserm UMRS1166, Sorbonne University, 75013 Paris, France
Department of Internal Medecine, Foch Hospital, 92150 Suresnes, France
AP-HP Pitié Salpêtrière-Charles Foix University Hospital, Functional Unit of Molecular and Cellular Cardiogenetics and Myogenetics, Department of Metabolic Biochemistry, 75013 Paris, France
AP-HP Cochin Hospital, Cardiology Department, FILNEMUS, Paris-Descartes, Sorbonne Paris Citeé University, 75006 Paris, France
AP-HP/LIB (INSERM-CNRS- Sorbonne University)/ICAN Imaging Core Lab, Institute of Cardiology, AP-HP Pitié Salpêtrière Hospital, Department of Cardiovascular Imaging, 75013 Paris, France
Paris Cardiovascular Research Centre (PARCC), Inserm UMRS970, 75015 Paris, France
Author to whom correspondence should be addressed.
Cells 2020, 9(3), 765;
Received: 3 February 2020 / Revised: 1 March 2020 / Accepted: 7 March 2020 / Published: 20 March 2020
Variants in LMNA, encoding A-type lamins, are responsible for laminopathies including muscular dystrophies, lipodystrophies, and progeroid syndromes. Cardiovascular laminopathic involvement is classically described as cardiomyopathy in striated muscle laminopathies, and arterial wall dysfunction and/or valvulopathy in lipodystrophic and/or progeroid laminopathies. We report unexpected cardiovascular phenotypes in patients with LMNA-associated lipodystrophies, illustrating the complex multitissular pathophysiology of the disease and the need for specific cardiovascular investigations in affected patients. A 33-year-old woman was diagnosed with generalized lipodystrophy and atypical progeroid syndrome due to the newly identified heterozygous LMNA p.(Asp136Val) variant. Her complex cardiovascular phenotype was associated with atherosclerosis, aortic valvular disease and left ventricular hypertrophy with rhythm and conduction defects. A 29-year-old woman presented with a partial lipodystrophy syndrome and a severe coronary atherosclerosis which required a triple coronary artery bypass grafting. She carried the novel heterozygous p.(Arg60Pro) LMNA variant inherited from her mother, affected with partial lipodystrophy and dilated cardiomyopathy. Different lipodystrophy-associated LMNA pathogenic variants could target cardiac vasculature and/or muscle, leading to complex overlapping phenotypes. Unifying pathophysiological hypotheses should be explored in several cell models including adipocytes, cardiomyocytes and vascular cells. Patients with LMNA-associated lipodystrophy should be systematically investigated with 24-h ECG monitoring, echocardiography and non-invasive coronary function testing. View Full-Text
Keywords: lipodystrophy; LMNA; cardiovascular disease lipodystrophy; LMNA; cardiovascular disease
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Mosbah, H.; Vatier, C.; Boccara, F.; Jéru, I.; Lascols, O.; Vantyghem, M.-C.; Fève, B.; Donadille, B.; Sarrazin, E.; Benabbou, S.; Inamo, J.; Ederhy, S.; Cohen, A.; Neraud, B.; Richard, P.; Picard, F.; Christin-Maitre, S.; Redheuil, A.; Wahbi, K.; Vigouroux, C. Looking at New Unexpected Disease Targets in LMNA-Linked Lipodystrophies in the Light of Complex Cardiovascular Phenotypes: Implications for Clinical Practice. Cells 2020, 9, 765.

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