Evaluation of somatic mutations in tibial pseudarthrosis samples in neurofibromatosis type 1

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. (By Dr. David Stevenson, http://jmg.bmj.com/content/early/2015/01/22/jmedgenet-2014-102815 )