Exome Sequencing Identifies The Predisposing Gene For A NF1Pedigree Combined With CPT

Background:The causes of congenital pseudarthrosis of tibia(CPT) is not entirely clear, many scholars have put forward a lot of etiology, pathology and genetics hypothesis and verified the related, but there is no clear convincing results. Nearly half in the CPT patients with neurofibromatosis type I performance, so some scholars at home and abroad for the research of the causes of CPT, think of the CPT pathogenesis may be associated with the disease genes of neurofibromatosis type I, but what form are there specific related with NF1haven’t be confirmed. This study have selected a family of three generations with a continuous neurofibromatosis type I, including two merged with congenital pseudarthrosis of tibia. On two combined with congenital pseudarthrosis of tibia family members for whole exome sequencing, through this method to find clues to the pathogenic mechanism of CPT.Objective:To explore the pathogenic gene of congenital pseudarthrosis of tibia.Methods:This study selected a family of three generations with a continuous neurofibromatosis type Ⅰ, including two merged with congenital pseudarthrosis of tibia. Included in the study are2patients with CPT, of2patients with CPT for whole exome sequencing, after get the purpose mutations, to Sanger sequencing directly and analysis of the gene cloning.Results:In the proband and patients with the same symptoms of congenital pseudarthrosis of tibia, after whole exome sequenced in all mutations selection gene NF1and relevant mutations in E775G (c.2324A>G) Sanger within for genealogy of this site again after verification, pedigree validation, function prediction, screening of polymorphic loci, the conservative projections. For the selected mutations E775G (c.2324A>G),2patients with congenital pseudarthrosis of tibia and2patients with neurofibromatosis type I skin milk coffee spot in the performance of the members are all in this mutation, and2without any clinical symptoms of normal family members did not find the existence of the mutation.Conclusion:1. This is the first time found new NF1gene mutations E775G(c.2324A>G) in the Chinese population;2. The mutations E775G (c.2324A>G) may leads to the development of CPT in the NF1family.