Campos, Julliane Tamara Araújo de MeloSena, Matheus Oliveira de2025-06-112025-06-112025-03-10SENA, Matheus Oliveira de. Lipomatose simétrica múltipla: diagnóstico genético e relação genótipo/fenótipo de variantes patogênicas no gene MFN2. Orientadora: Dra. Julliane Tamara Araújo de Melo Campos. 2025. 104f. Dissertação (Mestrado em Bioquímica e Biologia Molecular) - Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, 2025.https://repositorio.ufrn.br/handle/123456789/63924Multiple Symmetric Lipomatosis (MSL), also known as Madelung's disease or LaunoisBensaude disease, consists of a rare genetic disease with an autosomal recessive or compound heterozygous character that affects adipose tissue and is also characterized as a rare mitochondrial syndrome. MSL, genetically caused by a pathogenic variant in the MFN2 gene (c.2119 C>T; p.Arg707Trp), has already been phenotypically characterized by the development of non-encapsulated lipomas, mainly in the upper region of the trunk, highlighting the neck, supraclavicular and interscapular regions, commonly associated with axonal neuropathy, metabolic complications such as hypertriglyceridemia, decreased HDL-c, hypoadiponectinemia and hypoleptinemia in addition to mitochondrial disorders. Patients' history of excessive alcohol consumption has been associated with the accelerated development of LSM. It is worth mentioning that other variants were found in patients with LSM, such as the pathogenic variants c.1027_1029delAGG (p.Arg343del), c.600_816del (exons 7 and 8 deletion) and c.1496-2A>G, all found in compound heterozygosity together with pathogenic variant c.2119 C>T (p.Arg707Trp). Furthermore, several other pathogenic variants have already been described in the MFN2 gene. Still, only c.2119 C>T (p.Arg707Trp) in homozygosity or compound heterozygosity (along with the variants c.1027_1029delAGG, c.600_816del and c.1496-2A>G) were reported to determine the development of LSM, while the vast majority of other variants described in the gene are known to cause the axonal neuropathy called Charcot-Marie-Tooth type 2 (CMT2). The clinical manifestations of LSM present a significant heterogeneity, which is reflected in the chronology of their appearance and severity. In this study, we performed the 16th diagnosis of MFN2-associated MSL worldwide, the first in Brazil, in which the c.2119C>T variant was identified in homozygosis. The patient had low serum levels of adiponectin, leptin and HDL-c, in addition to hyperglycemia. The genotype x phenotype relationship of this patient with other already described in the literature was established. Using bioinformatic tools, simulations of three-dimensional structure, prediction of membrane topology and homotypic and heterotypic protein-protein interactions were performed for the wild type and mutants of mitofusin 2. In addition, an interaction network of MFN2 gene was made, in which the most enriched biological processes involving this gene were observed.pt-BRAcesso AbertoLipomatose simétrica múltiplaLipomasTecido adiposomasterThesisCIENCIAS BIOLOGICAS::BIOQUIMICA