prof. dr. T. Kleefstra (Tjitske)
Principal Investigator - Donders Institute for Brain, Cognition and Behaviour
Hoogleraar - Faculteit der Medische Wetenschappen (Radboudumc)
Our key ambition is to improve diagnostics, management and treatment of patients with monogenetic causes of neurodevelopmental Disorders (NDs), also referred to as Mendelian syndromes. Although Neurodevelopmental disorders likely affect 1-3% of the population and disrupt daily lives of patients and their caregivers, therapeutic management presently lacks effective intervention tools which is mainly due to the unknown etiology in about 50% of the affected and to the rareness of individual mutations. Thus, there is a strong need for knowledge enhancement regarding the genetic etiology and pathological mechanisms brought about by gene mutations. We aim to resolve the biological and clinical significance of genomic defects causing NDs. By implementing an innovative interdisciplinary program we will develop individual approaches in the treatment and management of NDs and be able to construct a concept of personalized healthcare for NDs. Next generation sequencing has recently revolutionized identification of causative genetic mutations in NDs. Our work and that of others has shown that for a considerable number of individuals with NDs, a molecular diagnosis can be provided. As a consequence, it is now possible to identify individuals with NDs sharing the same molecular defect. Thus, there is a strong need for knowledge enhancement regarding the pathological mechanisms brought about by gene mutations and study detailed phenotypes and correlate cognitive testing to address which specific cognitive parameters are affected, especially duriong lifespan. This allows a precise definition of cognitive endophenotypes rather than making the generalized definition of NDs. Within our research team we aim to fill this gap by applying innovative genotype-cognitive phenotype connections in NDs across lifespan, to generate conceptual knowledge about the molecular and cellular mechanisms underlying cognitive functions and in the development of intervention tools.