Recent developments in neurofibromatosis type 1 : Current Opinion in Neurology (original) (raw)

Developmental disorders

aDepartment of Medical Genetics, National Taiwan University Hospital, National Taiwan University School of Medicine, Taipei, Taiwan

bDepartment of Molecular Neuroscience, Institute of Neurology, University College London, London, UK

Correspondence to Dr Ming-Jen Lee, Department of Medical Genetics, National Taiwan University Hospital, No.7, Chung-Shan South Road, Taipei 100, Taiwan Tel: +886 2 23123456 ext 6698; fax: +886 2 23813690; e-mail: [email protected]

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 café-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.