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

Héléna Mosbah (1, 2) , Camille Vatier (1, 2) , Franck Boccara (2, 1) , Isabelle Jéru (2, 1) , Olivier Lascols (1, 2) , Marie-Christine Vantyghem (3, 4) , Bruno Fève (1, 2) , Bruno Donadille (1, 2) , Elisabeth Sarrazin (5, 6) , Sophie Benabbou (5, 6) , Jocelyn Inamo (5, 6) , Stephane Ederhy (2, 7) , Ariel Cohen (2, 7) , Barbara Neraud (8) , Pascale Richard (9, 7, 9) , Fabien Picard (10, 11) , Sophie Christin-Maitre (2) , Alban Redheuil (7, 12, 13, 9) , Karim Wahbi (10, 11, 14) , Corinne Vigouroux (1, 2, 2)

1 CRSA - Centre de Recherche Saint-Antoine
2 CHU Saint-Antoine [AP-HP]
3 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
4 RTD - Recherche translationnelle sur le diabète - U 1190
5 CHU de la Martinique [Fort de France]
6 Hôpital Pierre Zobda-Quitman [CHU de la Martinique]
7 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
8 Hôpital Foch [Suresnes]
9 CHU Pitié-Salpêtrière [AP-HP]
10 Hôpital Cochin [AP-HP]
11 FILNEMUS - Filière Neuromusculaire
12 Institut de cardiologie [CHU Pitié-Salpêtrière]
13 LIB - Laboratoire d'Imagerie Biomédicale [Paris]
14 PARCC (UMR_S 970/ U970) - Paris-Centre de Recherche Cardiovasculaire

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

Mots clés: LMNA; cardiovascular disease; lipodystrophy

Domaines: Sciences du Vivant [q-bio]; Médecine humaine et pathologie

Héléna Mosbah, Camille Vatier, Franck Boccara, Isabelle Jéru, Olivier Lascols, et al.. Looking at New Unexpected Disease Targets in LMNA-Linked Lipodystrophies in the Light of Complex Cardiovascular Phenotypes: Implications for Clinical Practice. Cells 2020, 2020, 9 (3), pp.765. ⟨10.3390/cells9030765⟩. ⟨hal-02586223⟩