Abstract 12: Whole exome sequencing of mother son duo identifies a novel variant p.E1415G in NF1 gene associated with neurofibromatosis

Background: Neurofibromatosis type 1 (NF1) is a common dominant inherited disorder with highly variable expressivity. The highly variable clinical features of NF1 are because of there are many genetic modifiers that lie outside the NF1 gene, which influence NF 1 gene and account for a large fraction of the symptomatic variability seen in NF1. Mutation detection in the NF1 gene is complex due to its large size, the existence of several pseudo genes and the lack of clustering of the mutations. There are no clear mutation hotspots and the spectrum of mutations is very diverse, ranging from micro deletions affecting the entire NF1 gene to minor lesions that include a high proportion of splicing mutations. Objective: Identification of the genetic mutation in mother son duo with neurofibromatosis. Method: Whole exome analysis was performed to identify the genetic defect. The variants were prioritized using standard open-source computational pipelines. Results: Whole exome sequencing and computational analysis identified a novel missense (c.4244A>G) at 17q11.2 cytogenetic location of NF 1 gene. Despite having the same genetic variant, absence ofpheochromocytoma in mother indicates heterogeneous presentation of neurofibromatosis type 1. Conclusion: To the best of our knowledge, this is the first report describing neurofibromatosis due to novel frameshift ANOS1 gene mutations. The report also exemplifies poor correlation of genotype and phenotype in neurofibromatosis cases.