Grant: Master's Award: Canada Graduate Scholarships

It was recently established that mutations in the genes POLR3A and POLR3B are responsible for three forms of childhood-onset leukodystrophies: Tremor Ataxia with Central Hypomyelination (TACH), Hypomyelination, Hypodontia and Hypogonadotropic hypogonadism (4H syndrome) and Leukodystrophie with oligodontia (LO). These genes encode two important components of the Pol III complex, which transcribes specific types of DNA into RNA. In this research project, we propose to study the impact of the mutations in POLR3A and POLR3B on Pol III function. First, we will establish whether mutations in genes encoding other components of Pol III can also cause these leukodystrophies. Secondly, we will determine whether the mutations affect the transcription efficiency of Pol III and the expression level of its targets. This research project will hopefully improve the understanding of this devastating orphan neurodegenerative disorder. It could also allow the identification of targets for therapeutic interventions.