B3541 - Tackling genetic and phenotypic heterogeneity of neurodevelopmental disorders - 19/05/2020

B number: 
Principal applicant name: 
Thomas Bourgeron | Institut Pasteur (France)
Thomas Rolland, Claire Leblond, Freddy Cliquet, Alexandre Mathieu, Roberto Toro, Guillaume Dumas, Julien Fumey, Andres Roman-Urrestarazu, Varun Warrier, Simon Baron-Cohen
Title of project: 
Tackling genetic and phenotypic heterogeneity of neurodevelopmental disorders
Proposal summary: 

In the last 20 years, there was a tremendous progress in identifying genetic risk factors for autism or neurodevelopmental disorders (NDDs) such as intellectual disability and epilepsy. If mutations affecting synaptic or chromatin remodelling genes are now well accepted as susceptibility factors for autism and NDDs, many key questions remain unanswered: (i) What is the interplay between the common and the rare genetic variants ? (ii) What are the genetic and environmental factors that influence the clinical trajectories of the patients? (iii) What are the specific brain processes involved? To address some of these questions, we will investigate the genetic and phenotypic data of the ALSPAC cohort to understand how genetic mutations in autism/NDD associated genes can have different consequences on the cognitive development of the individuals depending on the genetic and environmental background. Beyond improving our knowledge on the genetic architecture of autism/NDDs, our project should also lead to the identification of protective factors explaining how some individuals are resilients to strongly deleterious mutations.

Impact of research: 
This project addresses questions that are recurrently asked by clinical geneticists working in the field of NDDs. When a mutation is detected, what is the outcome of the patient? Can we have a better prediction of the clinical trajectory of the patients? We will provide a better genetic and phenotypic characterization of the carriers of the deleterious mutations and identify “protective factors” that could compensate the severity of the mutation. Beyond improving our understanding of NDDs, our project holds the promise of a true personalized medicine and new venues for drug development such as early patient stratification in clinical trials.
Date proposal received: 
Monday, 18 May, 2020
Date proposal approved: 
Tuesday, 19 May, 2020
Mental health - Psychology, Psychiatry, Cognition, Developmental disorders - autism, Computer simulations/modelling/algorithms, Genetics