A whole-exome sequencing (WES) study on 213 melanomas found that NF1, encoding a negative regulator of RAS mutated in Neurofibromatosis type 1, is the third most frequently mutated gene in melanoma, after BRAF and NRAS. Inactivating NF1 mutations were present in 46% of melanomas expressing wild-type BRAF and RAS, occurred in older patients and showed a distinct pattern […]

Bohring-Opitz Syndrome (BOS, MIM 612990) is a rare condition characterized by dysmorphic features, failure to thrive, severe intellectual disability,  nevus flammeus and myopia. It can be caused by heterozygous mutations in ASXL1, a gene involved in the regulation of Hox genes. Russel et al. (AJMG, 2015, Apr 29. doi: 10.1002/ajmg.a.37131. [Epub ahead of print]) just published clinical management […]

Neurofibromatosis type-1 (NF1) can present with focal skeletal dysplasias that remain extremely difficult to treat. Elefteriou and colleagues report that ablation of Nf1 in bone-forming cells results in accumulation of pyrophosphate (PPi), a strong inhibitor of hydroxyapatite formation, and that a chronic extracellular signal–regulated kinase (ERK)-dependent increase in expression of genes promoting PPi synthesis and extracellular transport, namely Enpp1 […]

A recent paper in the Journal of Clinical Investigation identified targets for therapy of malignant peripheral nerve sheath tumors (MPNST) in patients with Neurofibromatosis type 1 (NF1). These incurable peripheral nerve tumors result from loss of NF1 tumor suppressor gene function, causing hyperactive Ras/Raf/MEK/ERK signaling. PD0325901, a highly selective pharmacological inhibitor of MEK, reduced aberrantly […]