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Orphanet References OMIM Gene GeneReviews HGMD HGNC
last update : 30-08-2016
Symbol NF1
Location 17q11.2
Name neurofibromatosis 1 (von Recklinghausen disease)
Corresponding gene NF1
related resource Neurofibromatosis Type I
Main clinical features
  • characterized by café au lait spots, axillary freckling, Lisch nodules of the iris, multiple neurofibromas, presumably arising from NF1 inactivation in Schwann cells, tibial pseudarthrosis and a predisposition to certain benign and malignant tumors of the central and peripheral nervous system, with a variable expression even among relatives, bearing with the same mutation and apparently an earlier onset or a more severe form associated with deletions
  • specific deficits in the domains of visuospatial and executive functions are among the most common cognitive deficits associated, hypoactivation of corticostriatal structures leading to working memory deficits (PMID: 20624961)), mild mental retardation (prevalence of the cognitive deficits approaches 70p100) (PMID: 23312374))
  • Genetic determination autosomal dominant
    Prevalence 1/3000 (PMID: 20624961)
    Related entries . neurofibrosarcoma (see TSG17C) allelic loss, only in plexiform tumor in malignant tumors . Watson syndrome . pulmonic stenosis with cafe-au-lait spots . cafe-au-lait spots with pulmonic stenosis
    Function/system disorder neurology
    Type disease
    Gene mutationChromosome rearrangementEffectComments
    nonsense   truncated protein  
      deletion   see NF1DEL
  • mostly truncating mutations due to frameshift, non sense, missense mutations resulting in alteration of mRNA splicing, may be with a participation of the embedded genes EVI2A, OMGP, EVI2B in cases of large deletions, somatic mutations in segmental neurofibromatosis
  • functional tetranucleotide (AAAT) polymorphism in an Alu element in the NF1 gene is associated with mental retardation (PMID: 21236316))
  • significant overexpression of specific cancer-associated genes in pseudoarthrosis highlights a potential for receptor tyrosine kinase inhibitors to target NF1-deficient pseudoarthrosis and promote proper bone remodeling and fracture healing (PMID: 24932921))
  • Genotype/Phenotype correlations
  • inframe deletion (c.2970-2972 delAAT) in exon 17, associated to absence of cutaneous neurofibromas
  • NF1 missense mutations, although located outside the GAP-related domain, may be an important risk factor for a severe presentation (PMID: 29290338))