fig1

Figure 1. Schematic overview of the potential and utility of induced pluripotent stem cell (iPSC) in precision medicine. In the first step the likely pathogenic variant is identified using, e.g., next-generation sequencing technologies with DNA isolated from peripheral blood. In case of a variant without a known function loss-of-function or gain-of-function and/or for drug screening, primary fibroblast cultures are established from patient skin biopsies and reprogrammed into human induced pluripotent stem cell (hiPSC). The pathogenic variant can then be corrected using CRISPR/Cas9 gene editing, which generates isogenic controls for the patient hiPSCs with the pathogenic variant. Both hiPSCs are subsequently differentiated into relevant neurons (gluatamatergic or GABAergic in case of monogenic epilepsies) or cerebral organoids, which can be used in electrophysiological studies to determine the functional consequences and/or in drug screening