Objective: Discover the importance of genome regulation mechanism and accompanying transcriptional responses in the onset of rare neurodevelopmental genetic diseases.

Outcomes: The project resulted in generation of a battery of human stem cells from healthy individuals and patients. This served as basis for disease modelling in 2D and 3D organoid models. Through 7 publications focusing on rare conditions caused by HUWE1, OXR1 and UCHL1 deficiencies we demonstrated that: (I) increased oxidative stress characterizes different neurodevelopmental diseases; (II) p53 signalling is frequently deregulated in severe syndromes; (III) OXR1A is a novel regulator of histone arginine methylation and growth hormone production; (IV) altered ubiquitin processing affects neurodevelopment; (V) general and region specific organoids provide unique insights into human rare genetic diseases. The work on genome regulation and modeling of rare genetic diseases presented basis for establishing of Clinical Academic Group (CAG) for Rare Genetic Diseases in 2021. The goal of CAG is to build clinical and academic competence in diagnostics and management of patients, as well as gene- and cell- based therapies of rare genetic diseases.