In a more physiologic overexpression system, we integrated pB-NGN2 into iPSCs reprogrammed from female27 and male28,29 Iowa kindred patients harboring SNCA gene triplication with concomitant dementia and parkinsonism associated with diverse pathologies.30,31 Isogenic allelic series were generated through CRISPR-Cas9 engineering (SNCA “4-copy” parental, wild-type “2-copy” knockdown, and null “0-copy” knockout) (Figures 1G, top, and 2A, left). This evidence concerns the gene NEUROG2 and Parkinson disease.