Donders Institute for Brain, Cognition and Behaviour
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Thesis defense Britt Mossink (Donders series 513)

Date: 27 September 2021

Promotors: Prof. Dr. J.H.L.M. van Bokhoven, Dr. N. Nadif Kasri
Co-promotors: Dr. D. Schubert

The cell-type specific contribution of EHMT1 to neuronal network dysfunction in Kleefstra Syndrome

In our brain, every neuronal network not only has a function, but also a history across development. Errors that occur during the development of these networks can severely impact how a person develops and behaves in their adult life. To improve the quality of life for patients with these neurodevelopmental disorders, research into the disease-causing mechanisms and possible disease modifying treatments is required. Therefore, stem cells were used to develop a human model that allowed the investigation of neuronal network function of Kleefstra syndrome patients outside the body. Mutations in EHMT1 causing Kleefstra syndrome were studied in several types of human brain cells, and how this affected their interaction in a network. The results revealed that each cell-type has an important contribution to altered neuronal network function in Kleefstra Syndrome. Furthermore, several molecular targets were identified that might serve as a promising starting point for follow-up research into possible therapeutic interventions.