Importance of the field: Neurofibromatosis type 1 (NF1) is a familial tumour predisposition syndrome with no current treatment regime. Neurofibromin, the NF1 gene product, is a Ras-GAP protein that downregulates Ras and when inactivated leads to increased cell growth, proliferation and eventually tumorigenesis. The Ras family proteins have a central role in cell biology and are of prime importance in cancer development.
Areas covered in this review: This article reviews recent advances from the past 5 years, covering aspects of molecular and clinical diagnosis of NF1, genotype/phenotype studies, the RASopathies, NF1 tumorigenesis, mouse NF1 models and potential therapies. What reader will gain: The reader is introduced to recent advances in NF1 that focus on clinical and molecular diagnosis. The reader should gain a better understanding of the molecular basis of NF1 and of other NF1-like syndromes, and the challenges presented for clinical management.
Take home message: A molecular diagnosis can usually be made in most NF1 patients using a battery of gene screening techniques. The sensitivity and specificity of mutation detection will increase with the introduction of new technologies and new bioinformatic tools. Pathogenic somatic mutations of the NF1 gene are increasingly being identified in tumours not usually associated with NF1, a clear indication that neurofibromin has a much wider biological role and has an importance far beyond NF1.