Caractérisation clinique et génétique des malformations cérébrales

 

Myriam Srour

Institut de recherche du Centre universitaire de santé McGill

 

Domaine : génétique humaine

Programme Chercheurs-boursiers cliniciens - Junior 2

Concours 2019-2020

My research program is centered on the study of the genetic and physiological mechanisms underlying two disorders of brain development:

  1. Focal Cortical Dysplasias (FCDs) are groups of abnormal disorganized cells in the brain, and are the most common cause of intractable epilepsy. Mutations that arise in the fetus in genes of the molecular pathway called ‘mTOR' are responsible for some FCDs. These mutations only affect a small number of brain cells, therefore are not detectable by standard genetic testing. These early findings are especially exciting as medications directly targeting the mTOR pathway are available. Using novel sequencing methods, I will investigate what proportion of FCD cases are caused by mTOR pathway mutations, determine in which cell-type these mutations occur, and discover novel FCD genes.
  2. Congenital Mirror movements (CMM) are involuntary movements on one side of the body that mirror the contralateral voluntary ones. This unusual disorder is caused by the abnormal crossing of motor pathways of the nervous system. I discovered the first known CMM gene: DCC. Animals with DCC mutations also show disturbances of gait and sensation. However, DCC's role in these systems has never been studied in humans. I have collected the world's largest CMM cohort which includes 90 individuals. Of these, 40 have DCC mutations, 3 have other gene mutations, and 47 are genetically unexplained. Using this unique cohort, I will identify novel genes responsible for CMM, and study the role of DCC on sensation and gait in humans.

Understanding the genetic and pathophysiologic basis of disorders of brain development is essential for patients, as it allows specific diagnosis, optimizes clinical management, and allows precise genetic counseling. Most critically, understanding the genetic and physiologic basis of these disorders is the essential step to developing novel targeted treatments.