Abstract: Heterozygous de novo mutations in the PURA gene cause PURA syndrome, a neurodevelopmental disorder characterized by neurodevelopmental delay, intellectual disability, hypotonia and epileptic seizures. Besides its nucleic acid binding ability, PURA’s molecular role in cells is poorly understood. To model PURA syndrome in vitro, homozygous knock-out (KO) iPS cell lines and reprogrammed patient iPS cell lines harboring the most recurrent PURA mutation (Phe233del) were generated as well as their respective isogenic controls. The iPSCs were differentiated into cerebral organoids to study the impact of PURA’s absence and the effect of Phe233del mutation during early neurodevelopment. While morphological and size analysis of the organoids showed no difference between KO, patient cells, and their isogenic controls, multi-omic approaches revealed significant cellular changes in early development upon loss of PURA.
Funding Source: DFG - Deutsche Forschungsgemeinschaft
