title: Dissecting Clinical Heterogeneity in Neurofibromatosis Type 1.
abstract: Neurofibromatosis type 1 (NF1) is a common neurogenetic disorder in which affected children and adults are predisposed to the development of benign and malignant nervous system tumors. Caused by a germline mutation in the NF1 tumor suppressor gene, individuals with NF1 are prone to optic gliomas, malignant gliomas, neurofibromas, and malignant peripheral nerve sheath tumors, as well as behavioral, cognitive, motor, bone, cardiac, and pigmentary abnormalities. Although NF1 is a classic monogenic syndrome, the clinical features of the disorder and their impact on patient morbidity are variable, even within individuals who bear the same germline NF1 gene mutation. As such, NF1 affords unique opportunities to define the factors that contribute to disease heterogeneity and to develop therapies personalized to a given individual (precision medicine). This review highlights the clinical features of NF1 and the use of genetically engineered mouse models to define the molecular and cellular pathogenesis of NF1-associated nervous system tumors.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110; email: gutmannd@wustl.edu.
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Monroe
authors.affiliation: Division of Neuropathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Sonika
authors.initials: S
authors.lastname: Dahiya
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110; email: gutmannd@wustl.edu.
authors.forename: David H
authors.initials: DH
authors.lastname: Gutmann
mesh_terms: D000328:Adult; D000818:Animals; D004195:Disease Models, Animal; D016514:Genes, Neurofibromatosis 1; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D051379:Mice; D009456:Neurofibromatosis 1 / Q000145:classification* / Q000235:genetics* / Q000473:pathology
keywords: NF1; brain tumors; neurofibroma; optic pathway glioma; precision medicine