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

Grant number: 17/00648-1
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2017
Effective date (End): February 29, 2020
Field of knowledge:Health Sciences - Medicine
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Iscia Teresinha Lopes Cendes
Grantee:Helena Tadiello de Moraes
Home 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


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)