Lipodistrofias relacionadas a variantes patogênicas do gene CAV1: uma análise fenotípica e genotípica de três tipos distintos

Abstract

Lipodystrophies are a heterogeneous group of rare diseases. Their carriers present a reduced amount of subcutaneous white adipose tissue as the main symptom. However, they also experience systemic alterations similar to those seen in obesity-related metabolic syndrome, including type 2 diabetes mellitus, non-alcoholic fatty liver disease, hyperinsulinemia, and dyslipidemia. In some cases, these conditions can progress to more serious systemic complications. Lipodystrophies can be mainly classified into two large groups: congenital generalized lipodystrophies and familial partial lipodystrophies. Within these large groups, two types occur due to different mutations in the same gene, CAV1. These types are known as congenital generalized lipodystrophy type 3 and familial partial lipodystrophy type 7. Recently, a new type of lipodystrophy syndrome associated with neonatal progeroid syndrome has been classified involving a pathogenic variant in CAV1. This gene is responsible for encoding the protein caveolina-1, which plays a crucial role as an essential component of caveolae. They are small invaginations in the plasma membrane that have diverse functions in cell metabolism. Due to the rarity of this disease there have been limited studies correlating the genotypes and phenotypes observed in patients. Consequently, the understanding of how the structural changes caused by mutations in the caveolina-1 protein interfere with the metabolism of affected individuals remains limited. The objective of this study is to analyze the genotype and phenotype of patients who have been well-documented in the literature with these three different types of lipodystrophies, as well to understand the role of caveolina-1 and caveolae in metabolism.