Genotype-phenotype associations in neurofibromatosis type 1 (NF1): an increased risk of tumor complications in patients with NF1 splice-site mutations?

摘要: Neurofibromatosis type 1 (NF1) is a complex neurocutaneous disorder with an increased susceptibility to develop both benign and malignant tumors but wide spectrum of inter intrafamilial clinical variability. The establishment genotype-phenotype associations in NF1 potentially useful for targeted therapeutic intervention has generally been unsuccessful, apart from small subsets molecularly defined patients. objective this study was evaluate the phenotype associated specific types mutation retrospectively recorded dataset comprising 149 mutation-known individuals unrelated families. Each patient assessed ten NF1-related features, including number cafe-au-lait spots, cutaneous subcutaneous neurofibromas presence/absence intertriginous skin freckling, Lisch nodules, plexiform spinal neurofibromas, optic gliomas, other neoplasms (in particular CNS peripheral nerve sheath (MPNSTs), juvenile myelomonocytic leukemia, rhabdomyosarcoma, phaechromocytoma, gastrointestinal stromal tumors, xanthogranuloma, lipoma) evidence learning difficulties. Gender age at examination were also recorded. Patients subcategorized according their germ line mutations: frame shift deletions (52), splice-site mutations (23), nonsense (36), missense (32) (6). A significant association apparent between possession presence brain gliomas MPNSTs (p = 0.006). If confirmed, these findings are likely be clinically important since up third patients harbor mutations. influence gender observed on (females, p 0.009) preschool difficulties 0.022).