Recent developments in neurofibromatosis type 1
Journal
Current Opinion in Neurology
Journal Volume
20
Journal Issue
2
Pages
135-141
Date Issued
2007
Author(s)
Stephenson D.A.
Abstract
PURPOSE OF REVIEW: This review summarizes the recent clinical and genetic developments in neurofibromatosis type 1 (NF1) and provides an insight into the possible underlying pathomechanisms. RECENT FINDINGS: NF1, or von Recklinghausen disease, is one of the most common hereditary neurocutaneous disorders in humans. Clinically, NF1 is characterized by caf?-au-lait spots, freckling, skin neurofibroma, plexiform neurofibroma, bony defects, Lisch nodules and tumors of the central nervous system. The responsible gene, NF1, encodes a 2818 amino acid protein (neurofibromin). Pathological mutations range from single nucleotide substitutions to large-scale genomic deletions dispersed throughout the gene. In addition to the conventional mutation screening methods, a DNA chip microarray-based technology, combinational sequence-based hybridization, has been introduced to expedite mutation detection. Functional analysis has become more amenable following the development of the following: (1) primary Schwann cell cultures from NF1 patients; (2) mouse models; (3) proteomic technologies; and (4) mRNA silencing by RNA interference. These studies have shown that neurofibromin plays a role in adenylate cyclase and AKT-mTOR mediated pathways. It also appears to affect Ras-GTPase activating protein activity through the phosphorylation of protein kinase C which impacts on cell motility by binding with actin in the cytoskeleton. SUMMARY: Recent advances in the clinical features and molecular genetics of NF1 will be discussed together with insights into the underlying pathomechanisms of NF1. ? 2007 Lippincott Williams & Wilkins, Inc.
SDGs
Other Subjects
actin; adenylate cyclase; amino acid; guanosine triphosphatase activating protein; mammalian target of rapamycin inhibitor; messenger RNA; neurofibromin; protein kinase B; protein kinase C; biotechnology; bone defect; bone disease; cafe au lait spot; cell culture; cell motility; central nervous system tumor; clinical feature; cognitive defect; combinatorial chemistry; cytoskeleton; disease model; DNA hybridization; DNA microarray; experimental mouse; functional assessment; gene deletion; gene mutation; gene silencing; genetic analysis; genetic disorder; genetic screening; genetics; genomics; human; lentigo; mental disease; molecular genetics; mutational analysis; neurofibroma; neurofibromatosis; neurologic disease; nonhuman; pathogenesis; phakomatosis; protein function; protein phosphorylation; proteomics; review; RNA interference; Schwann cell; signal transduction; single nucleotide polymorphism; skin manifestation; skin tumor; vascular disease; Animals; Disease Models, Animal; Humans; Mice; Models, Biological; Neurofibromatosis 1; Neurofibromin 1; Proteomics; RNA Interference
Type
review