Banca de QUALIFICAÇÃO: MARIANA NOVAES SANTOS

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : MARIANA NOVAES SANTOS
DATE: 30/05/2022
TIME: 09:00
LOCAL: Plataforma Teams
TITLE:

Familial Adenomatous Polyposis in Alagoas

KEY WORDS:

Hereditary Neoplastic Syndromes, Adenomatous Polyposis Coli, APC Genes, Rare Diseases.

PAGES: 48
BIG AREA: Ciências Biológicas
AREA: Genética
SUBÁREA: Genética Humana e Médica
SUMMARY:

Familial Adenomatous Polyposis (FAP) is a hereditary colorectal cancer syndrome caused by germline variants of APC gene, with autosomal dominant inheritance and nearly complete penetrance of colorectal cancer if left untreated. The global care of patients with FAP includes timely prevention, diagnosis and surgical intervention strategies. Thus, the reduction of systemic barriers in the access of patients to information and healthcare is critical to disease management. This research is the first step for the knowledge of the molecular epidemiology of hereditary colorectal cancer syndromes in Alagoas and it focuses on the study of a family with multiple individuals affected by intermediate FAP. It aims to describe clinical, socioeconomic and genetic characteristics of this family. Therefore, this cross-sectional and observational study enrolled 59 participants. Data was collected through an inhouse clinical and socioeconomic questionnaire, the Brazilian validated Health Literacy Test (from Portuguese, TLS) and the review of the medical records of the family members followed at the University Hospital of Federal University of Alagoas. Additionally, pedigree draft and biologic samples for family’s variant identification were obtained. Clinical data and the TLS scoring were recorded on Excel and will be descriptively analyzed using the statistical program EpiInfo. Socioeconomic data will be used for the Family Development Index calculation. Genes of interest were screened by next-generation sequencing in the index case. Results were confirmed through Sanger sequencing in the index case and allele-specific polymerase chain reaction (PCR) in four affected participants and three negative controls (intra and extrafamilial). In silico pathogenicity prediction analysis of the identified variant was performed. The APC heterozygous germline variant c.1255del (p.Thr419Profs*35), which has never been previously reported, was identified in the affected participants. In silico analysis confirmed the pathogenicity of the genetic alteration, since it leads to early truncation and loss of all functional domains of APC protein. Two hundred and fifty individuals, with 28 living affected relatives, were mapped through the pedigree analysis, which confirms the autosomal dominant segregation of the variant within the family. The genotype-phenotype correlation is consistent with the literature, which reports association between alterations located from codons 157 to 1250 and intermediate intestinal polyposis.

BANKING MEMBERS:
Presidente - 3221982 - ISABELLA LOPES MONLLEO
Interna - 2269479 - CAROLINNE DE SALES MARQUES
Interna - 2370894 - MICHELLE JACINTHA CAVALCANTE OLIVEIRA
Interno - 384.145.544-15 - SAMIR BUAINAIN KASSAR - UNCISAL
Externo à Instituição - BENEDITO MAURO ROSSI