Investigating a polygenic effect in genomic data of patients with childhood epileptic encephalopathies (CEE)

• Grant number: 17/00648-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2017
• End date: February 28, 2022
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Iscia Teresinha Lopes Cendes
• Grantee: Helena Tadiello de Moraes
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/07559-3 - BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology, AP.CEPID

Abstract

Childhood epileptic encephalopathies (CEEs) is a group of severe epilepsies that are resistant to drug treatment and associated with delayed neuropsychological, motor and cognitive development. The diagnosis of CEE is still based on clinical criteria and electroencephalogram results and the etiology remains unknown in most patients. With the progress of molecular studies, in the last five years new mutations associated with CEE have been described. However, a significant portion of the patients still do not have a major genetic variant identified (assuming a monogenic inheritance model) even after whole human exome sequencing. Thus, the main objective of this work is to apply new analytical paradigms to identify and investigate genetic changes following complex inheritance models. We will use whole exome sequencing data from a large cohort of CEE patients. Our proposal will apply algorithms that allow us to consider a polygenic and cumulative effect on genes in the same or different molecular pathways, but with potential additive effect in the phenotype. At the end of our work, we will have applied and tested the original hypothesis that cases of CEE can be caused by mutations with small individual effects, occurring in several genes of a common pathway or in pathways that may converge to a major final effect on the phenotype. This work has the potential to change the entire analytical paradigm currently used in the molecular diagnosis of CEEs leading to valuable information about the etiology and molecular diagnosis of these severe forms of epilepsy. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MAGALHAES, PEDRO H. M.; MORAES, HELENA T.; ATHIE, MARIA C. P.; SECOLIN, RODRIGO; LOPES-CENDES, ISCIA. New avenues in molecular genetics for the diagnosis and application of therapeutics to the epilepsies. Epilepsy & Behavior, v. 121, n. B, AUG 2021. (13/07559-3, 17/00648-1, 13/19524-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MORAES, Helena Tadiello de. Genetic characterization of a Latin American cohort of patients with developmental and epileptic encephalopathies. 2022. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.