Banca de QUALIFICAÇÃO: MONIQUE ALVARES DA SILVA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : MONIQUE ALVARES DA SILVA
DATE: 27/11/2023
TIME: 09:00
LOCAL: Videoconferência - Link para acesso: https://meet.google.com/wzz-zjrz-giy
TITLE:

GENETIC DIAGNOSIS AND BIOINFORMATICS ANALYSIS OF VARIANTS OF THE PPARγ GENE, PRECURSOR OF PARTIAL FAMILY LIPODYSTROPHY TYPE 3 IN PATIENTS FROM NORTHEAST BRAZIL

KEY WORDS:

lipodystrophy, PPARγ, hypertriglyceridemia, adiposetissue.

PAGES: 77
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Lipodystrophy type 3 (FPLD3) has been described as molecularly associatedwith the PPARγ gene,with predominantly missensevariants onchromosome3. The syndrome causes loss of adipose tissue in the upper and lower limbs, hips, and face. It is generally associated with metabolic disorders such as type 2 dia- betes, insulin resistance, hypertriglyceridemia, and liver dysfunction. Therefore, the objective of this work was to molecularly diagnose patients with suspected FPLD3 recruited by the endocrinology clinic of the Hospital Universitário Onofre Lopes. To this end, a clinical evaluation was carried out, oral swabs and blood samples were collected. Biochemical analyses and dosages of the hormones adiponectin and leptin were performed using the ELISA technique to evaluatethe metabolic disorders inherent to FPLD3. The next-generation sequencing (NGS) technique was chosen to diagnose the variants through a panel of genes relatedtolipodystrophiesincludingLMNAandPPARγ.ToconfirmtheNGSdata, amplification of genetic material was carried out by conventional PCR and San- ger sequencing using primers specifically designed for this work. The tools used for bioinformatic analysis of the variants were Poly-Phen2, TCoffee, and Muta- tion Taster. It was observed that the patients presented clinical characteristics compatible with the presence of lipodystrophy, such as loss of adipose tissue in the extremities, hypertriglyceridemia, and steatosis, in addition to a reduced adi- ponectin and leptin dosage within normal limits concerning the reference value for the index of corresponding body mass. Molecularly, new heterozygous vari- ants located at positions c.533T>C promoting the replacement of the amino acid leucine by proline at 178 (p.Leu178Pro) and c.641C>T promoting the replace- ment of the amino acid proline by leucine at 214 were identified and confirmed in three patients. (p.Pro214Leu). The variants respectively affect the DBD domainof the protein, responsible for binding PPAR to the promoter region of target genes, and the Hinge region, involved in the interaction with coactivators and corepressors. Through bioinformatic analysis of each identified variant and its comparative alignment with the wild type, it was observed that the scores corro- borated what was observed clinically, classifying the variants as harmful to their function.Noneofthevariantsfoundhavebeenpreviouslyreportedintheliteratu- re.

COMMITTEE MEMBERS:
Presidente - 1046922 - LEONARDO CAPISTRANO FERREIRA
Externa ao Programa - 2477216 - NAISANDRA BEZERRA DA SILVA FARIAS - nullExterno ao Programa - 2329140 - RAIMUNDO FERNANDES DE ARAUJO JUNIOR - null