Genotype-phenotype correlations and treatment innovation of neurofibromatosis type 1(NF1):Current understanding and perspective

Neurofibromatosis type 1(NF1)is an autosomal dominant inherited disease caused by mutations in the NF1 gene.It is characterized by cafe-au-lait macules(CALMs),cutaneous neurofibromas(CNF),plexiform neurofibromas(PNF),Lisch nodules,optic pathway gliomas(OPG),potential skeletal abnormalities,and other complications involving multiple organs and systems.[1]Additionally,approximately 10%of individuals with NF1 may progress to develop malignant peripheral nerve sheath tumors(MPNST).[1]The NF1 gene encodes neurofibromin,which regulates Ras and its downstream signaling pathways,such as the mitogen-activated protein kinase(MEK)/extracellular signal-regulated kinase(ERK)and phosphatidylinositol-3-kinase(PI3K)/Akt/mammalian target of rapamycin(mTOR)pathways.