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NF1 Somatic Mutation in Dystrophic Scoliosis


Scoliosis is a common manifestation of neurofibromatosis type 1, causing significant morbidity. The etiology of dystrophic scoliosis in neurofibromatosis type 1 is not fully understood and therapies are lacking. Somatic mutations in NF1 have been shown in tibial pseudarthrosis providing rationale for similar processes in neurofibromatosis type 1–associated dystrophic scoliosis. Spinal samples from surgical procedures with matched peripheral blood of two individuals with neurofibromatosis type 1 and dystrophic scoliosis were obtained and DNA extracted. Next generation sequencing of various spinal sections as well as the germline/blood sample were performed using a RASopathy gene panel (includes the NF1 gene). Variants were compared between the spinal tissue samples and the germline data. In addition, the next generation sequencing allele frequency data were used to detect somatic loss of heterozygosity. All samples had a detected potentially inactivating NF1 germline mutation. Both individuals demonstrated an allelic imbalance inclusive of NF1 in the next generation sequencing data. In addition, for the same two individuals, there was an increase in the % variant reads for the germline mutation in some of the surgical spinal samples corresponding to the allelic imbalance. Contra analysis did not show any deletion in Chromosome 17 next generation sequencing data. Microarray analysis verified somatic copy neutral loss of heterozygosity for these two individuals for the majority of the chromosome 17 q-arm, inclusive of the NF1 gene. These results suggest that the cause of dystrophic scoliosis is multifactorial and that a somatic NF1 mutation contributes to the etiology.

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The authors thank the Shriners Hospital for Children (Salt Lake City, UT) and their clinicians and coordinators including Stephen Santora, Michael Pond, Janice Davis, Jeanne Siebert, Susan Geyer, Kyle Berg, and Austin Stevens for their role in consenting and collecting surgical tissues and for their input.


This work was supported by grants from the Department of Defense (award W81XWH-11-1-250; David Stevenson, David Viskochil, and John Carey), and Shriners Hospital for Children (no. 9198; Jacques D’Astous, David Stevenson, John Carey, and David Viskochil). Portions of the research were supported by the University of Utah Clinical Genetics Research Program (David Viskochil) and the National Center for Research Resources and National Center for Advancing Translational Sciences at the National Institutes of Health (UL1RR025764).

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Correspondence to David A. Stevenson.

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Margraf, R.L., VanSant-Webb, C., Mao, R. et al. NF1 Somatic Mutation in Dystrophic Scoliosis. J Mol Neurosci 68, 11–18 (2019).

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  • Neurofibromatosis type 1
  • NF1
  • Scoliosis
  • Somatic mutation
  • Spine