Put together, these experiments verify that effects of trisomic DYRK1A dose and kinase activity on DDR derangement are reproducible in isogenic iPSC systems from two unrelated individuals, and that in the context of the full chr21 trisomy, DYRK1A dose and kinase activity are both necessary and sufficient to explain the increase in DSB in DS iPSCs. This evidence concerns the gene DYRK1A and Dravet syndrome.