Genetics and pathophysiology of neurodevelopmental Disorders

Neurodevelopmental disorders (NDDs) are a group of diseases that result from abnormalities during brain development that impair brain function. NDDs include intellectual disability and autism-spectrum disorders, which affect 1.5-2% of children or young adults. More than 1,000 genes are known to be involved in monogenic forms of NDD, coding for proteins involved in different cellular processes, with others yet to be identified. Identifying the genes involved in NDD and characterising the consequences of variants occurring in these genes is essential for families to obtain accurate molecular diagnosis and genetic counselling. The gene identities are also critical for researchers to understand the mechanisms important for brain development and  for applicability of potential therapies. The genotype/phenotype correlations and natural history of patients with these different genetic forms are not always well described, and little is known about the pathophysiological mechanisms involved. It is our hope that this knowledge will improve the patient outcomes and to help to develop novel therapeutic approaches.

The team is therefore interested in identifying new genes and new molecular mechanisms involved in NDD, in studying genotype/phenotype correlations and the natural history of patients with NDD, and in dissecting the pathophysiological mechanisms involved in certain frequent genetic mutations (fragile X syndrome, DYRK1A syndrome, etc). In the context of Fragile X syndrome, the team is involved in the development of a gene therapy strategy in collaboration with Lysogene SA. The team works in close interaction at the local level with different research teams from IGBMC and other research centers in Strasbourg and with clinical services from the University Hospital of Strasbourg thus favouring translational application of the research results. The team has also numerous national (IBPS, CRBM, etc) and international collaborations (Sick Children, DGIST, etc) and participates to different research and hospital networks on NDD.