NF1 Somatic Mutation in Dystrophic Scoliosis

AbstractScoliosis 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 inNF1 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 sam ple were performed using a RASopathy gene panel (includes theNF1 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 inactivatingNF1 germline mutation. Both individuals demonstrated an allelic imbalance inclusive ofNF1 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 m...

Source: Journal of Molecular Neuroscience - February 18, 2019 Category: Neuroscience Source Type: research