Strikingly, addition of BDNF, or pharmacological mimics such as amitriptyline, can compensate for CSB deficiency during neuronal differentiation, and SYT9 and BDNF are downregulated in CS patient brain tissue [58], indicating that suboptimal induction of neurotrophin-regulated gene expression programs, rather than DNA repair deficiency, underlies most neurological defects in CS. Here, SYT9 is linked to Cowden syndrome 1.