Genetic changes of both NF1 genes are postulated to be necessary for the development of tibial pseudarthrosis in individuals with neurofibromatosis type 1 (NF1). However, the tissue origin of the “second hit” mutation remains unclear. Macro-sections of tibial pseudarthrosis tissue were exome sequenced, as well as a blood sample from a child with NF1. A splice site mutation was identified in the blood and tibial pseudarthrosis sample representing a germline mutation, while a somatic stop mutation was identified in just the tibial pseudarthrosis sample. The somatic mutation was enriched in the pseudarthrosis proliferative soft tissue, but absent in cortical bone. (http://jmg.bmj.com/content/early/2015/01/22/jmedgenet-2014-102815 )