Preprint Article Version 1 NOT YET PEER-REVIEWED

Identification of One BOCR Mutation and Five NF1 Mutations in Male Patients with Neurofibromatosis Type 1 and Congenital Pseudarthrosis of the Tibia

Zhifan Zhou 1,2,3 , Yong Zeng 4 , Xinchun Wu 4 , Fei Li 4 , Xiaoyan Liu 1,2,3 , Lu Zhou 1,2,3 , Lihua Hou 1,2,3 , Silong Sun 5 , Lu Shen 1,2,3 , Zhangyuan Lin 4,*
  1. Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
  2. Hunan Province Key Laboratory in Neurodegenerative Disorders, Central South University, Changsha 410008, China
  3. State Key Laboratory of Medical Genetics, Changsha 410008, China
  4. Department of Orthopaedics, Xiangya Hospital, Central South University, #87 Xiangya Road, Changsha 410008, China
  5. BGI-Shenzhen, Shenzhen, Guangdong Province, 518083, China
Version 1 : Received: 7 September 2016 / Approved: 7 September 2016 / Online: 7 September 2016 (11:19:00 CEST)

How to cite: Zhou, Z.; Zeng, Y.; Wu, X.; Li, F.; Liu, X.; Zhou, L.; Hou, L.; Sun, S.; Shen, L.; Lin, Z. Identification of One BOCR Mutation and Five NF1 Mutations in Male Patients with Neurofibromatosis Type 1 and Congenital Pseudarthrosis of the Tibia. Preprints 2016, 2016090024 (doi: 10.20944/preprints201609.0024.v1). Zhou, Z.; Zeng, Y.; Wu, X.; Li, F.; Liu, X.; Zhou, L.; Hou, L.; Sun, S.; Shen, L.; Lin, Z. Identification of One BOCR Mutation and Five NF1 Mutations in Male Patients with Neurofibromatosis Type 1 and Congenital Pseudarthrosis of the Tibia. Preprints 2016, 2016090024 (doi: 10.20944/preprints201609.0024.v1).

Abstract

Neurofibromatosis type1 (NF1) is an autosomal dominant disorder caused by mutations in the NF1gene. Although congenital pseudarthrosis of the tibia (CPT) has frequently been associated with NF1, the underlying molecular mechanism of CPT in these NF1 patients is yet ill-understood. The aim of the present study was to detect NF1 mutations from genomic DNA and to harbor variants associated with CPT in NF1 patients. Whole-exome sequencing was first carried out with samples from two patients with CPT in one NF1 family, and a novel mutation c.2324A>G (p.E775G) in NF1 gene was identified. Additionally, a missense variant c.455C>T (p.P152L) in BCOR gene completely co-segregated with the CPT phenotype within this family. Subsequently, NF1 and NF2 genes in four other unrelated patients with both NF1 and CPT were screened using targeted sequencing. Four mutations in NF1 gene, including two known mutations (c.2288T>C/p.L763P, c.574 C>T/p.R192*) and two novel mutations (c.768delT/p.F256Lfs*25, c.2229_2230delTG/ p.V744Qfs*23) were detected. Further study confirmed that CPT was present in NF1 families, and NF1 mutations were closely associated with these complex phenotypes. Moreover, the data from the current study indicated that male gender might be a susceptibility factor for CPT in NF1. Therefore, we speculated that BCOR variants might be related to CPT phenotype among male NF1 patients.

Subject Areas

neurofibromatosis type 1; congenital pseudarthrosis of the tibia; whole-exome sequencing; targeted sequencing; BCOR

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