Banca de DEFESA: ANA CAROLINA COSTA CAVALCANTE

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : ANA CAROLINA COSTA CAVALCANTE
DATE: 30/03/2026
TIME: 10:00
LOCAL: Videoconferência
TITLE:

A novel pathogenic variant in the cav1 gene associated with congenital generalized lipodystrophy type 3: molecular, phenotypic, and bioinformatic characterization

KEY WORDS:

adipose tissue, Berardinelli-Seip syndrome, metabolic disorder, caveolin1, caveolae.

PAGES: 88
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Congenital generalized lipodystrophy type 3 (CGL3) has been described as molecularly associated with pathogenic variants in the CAV1 gene, which encodes the protein caveolin-1, a structural component of caveolae. In general, this syndrome causes generalized loss of subcutaneous adipose tissue (SAT), especially in the upper and lower limbs, and is frequently associated with metabolic disturbances such as type 2 diabetes mellitus (T2DM), insulin resistance (IR), hypertriglyceridemia, and hepatic abnormalities. Therefore, the aim of this study was to molecularly and phenotypically characterize a patient with a previous clinical diagnosis of CGL3, comparing her case with others previously reported in the literature, as well as performing bioinformatic analyses of the identified variant and comparing it with other variants already described for this lipodystrophy. Clinical evaluation, oral swab collection, and blood sampling were conducted. Next-generation sequencing (NGS) was employed to detect the variant using a gene panel related to lipodystrophies. Confirmation of the NGS findings was performed through conventional PCR using primers specifically designed for this study. The tools used for the bioinformatic analysis of genetic variants included T-Coffee, MutationTaster, DeepLoc 2.0, STRING, Cytoscape, AlphaFold, and ChimeraX. The patient exhibited clinical features consistent with CGL3, such as generalized loss of adipose tissue in the extremities, abdominal enlargement due to hepatic abnormalities, short stature, and low body weight. At the molecular level, a novel homozygous variant promoting complete loss of exon 3 of the CAV1 gene, designated c.196_537del, was identified and confirmed. The genotype– phenotype correlation of the patient was established in comparison with cases previously described in the literature. Bioinformatic analyses included predictions of pathogenic potential, comparative alignment with the wild-type sequence, prediction of subcellular localization for both wild-type and variant proteins, three-dimensional protein modeling, and assessment of homotypic and heterotypic protein–protein interactions involving wild-type caveolin-1 and its pathogenic variants. The results obtained were consistent with the clinical phenotype observed in patients with CGL3, reinforcing the classification of these variants as deleterious. This is the first study to molecularly and phenotypically characterize a case of CGL3 associated with the c.196_537del variant, thus contributing novel findings to the scientific literature.

COMMITTEE MEMBERS:
Externo ao Programa - 1451614 - JOSIVAN GOMES DE LIMA - nullPresidente - 1837354 - JULLIANE TAMARA ARAUJO DE MELO CAMPOS
Interno - 1046922 - LEONARDO CAPISTRANO FERREIRA
Externa à Instituição - VIRGINIA OLIVEIRA FERNANDES CORTEZ - UFC