Banca de DEFESA: MARIA EDUARDA CARDOSO DE MELO

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : MARIA EDUARDA CARDOSO DE MELO
DATE: 28/03/2024
TIME: 09:00
LOCAL: Videoconferência - Link para acesso: https://meet.google.com/pkk-itva-hfb
TITLE:

 

Analysis of pathogenic variants in AGPAT2 and biochemical-molecular evaluation of individuals with congenital generalized lipodystrophy types 1 and 2

KEY WORDS:

 

Adipose tissue; Congenital Generalized Lipodystrophies; AGPAT2; Pathogenic variants; Adipose tissue-related diseases.

PAGES: 146
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

 

Congenital Generalized Lipodystrophy (CGL) is a rare disease that causes the loss of adipose tissue (AT) throughout the body from birth. Patients with CGL have low levels of leptin and adiponectin (APN), important adipokines produced by AT. There are four types of CGL, with types 1 and 2 being responsible for more than 80% of the cases described in the literature and with patients already reported in northeastern Brazil. The molecular etiology for LGC 1 and LGC 2 is the presence of pathogenic variants (PVs) in the AGPAT2 and BSCL2 genes, respectively. This study carried out the molecular analysis of the main VPs described for AGPAT2 (c.366-588del, c.589-2A>G, c.646A>T, c.570C>A, c.369-372delGCTC, c.202C>T, c.514G>A, c.144C>A) and an analysis of the effects on their transmembrane and functional domains. The genotype vs phenotype relationship of the first patients described in the literature for the PVs in question demonstrates the relationship between molecular alterations and clinical symptoms, so that patients with PVs that more significantly affect the proteins show a higher rate of clinical symptoms. In addition, we performed the molecular diagnosis of two sisters with VPs in compound heterozygosity for c.299G>A and c.493-1G>C and a new patient described for the c.366-588del variant. Using next-generation sequencing (NGS), a panel of genes associated with adipose tissue-related diseases was analyzed in LGC patients, which showed the presence of different VPs for the BSCL2 gene. The comparative study of leptin and APN dosages between the LGC 1 and LGC 2 groups showed that LGC type 2 patients had lower leptin levels, while no differences were observed between APN dosages in these two groups. At the level of expression of enzymes involved in repairing oxidized DNA damage (APE-1, OGG1 and PPARG), no significant differences were observed between the LGC 1 and LGC 2 groups, although both types had higher levels of expression of these genes when compared to that observed in control individuals. This suggests that the different molecular etiology of the two types of LGC is not a significant parameter for altering redox homeostasis between these two groups. Further studies are needed to better understand the relationship between LGC and oxidative stress, DNA repair and cellular response.

COMMITTEE MEMBERS:
Presidente - 1837354 - JULLIANE TAMARA ARAUJO DE MELO CAMPOS
Interno - 1046922 - LEONARDO CAPISTRANO FERREIRA
Externa à Instituição - VIRGINIA OLIVEIRA FERNANDES CORTEZ - UFC