NF1 and brain neoplasm: Although somatic NF1 gene inactivation is required for NF1-related tumorigenesis [77], we could speculate that: (1) the observed higher rate of truncating mutations in NF1 may suggest that at least 50% loss-of-function is necessary to initiate tumorigenesis; (2) additional genetic modifiers unlinked to the NF1 locus might play a role in brain tumors, as we proposed for NF1-related moyamoya vasculopathy [78].