Abstract
Multiple symmetric lipomatosis (MSL) is characterized by upper-body lipomatous masses frequently associated with metabolic and neurological signs. MFN2 pathogenic variants were recently implicated in a very rare autosomal recessive form of MSL. MFN2 encodes mitofusin-2, a mitochondrial fusion protein previously involved in Charcot-Marie-Tooth neuropathy. To investigate the clinical, metabolic, tissular, and molecular characteristics of MFN2-associated MSL. We sequenced MFN2 in 66 patients referred for altered fat distribution with one or several lipomas or lipoma-like regions and performed clinical and metabolic investigations in patients with positive genetic testing. Lipomatous tissues were studied in 3 patients. Six patients from 5 families carried a homozygous p.Arg707Trp pathogenic variant, representing the largest reported series of MFN2-associated MSL. Patients presented both lipomatous masses and a lipodystrophic syndrome (lipoatrophy, low leptinemia and adiponectinemia, hypertriglyceridemia, insulin resistance and/or diabetes). Charcot-Marie-Tooth neuropathy was of highly variable clinical severity. Lipomatous tissue mainly contained hyperplastic unilocular adipocytes, with few multilocular cells. It displayed numerous...Continue Reading
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