Mutations in von Recklinghausen neurofibromatosis: an hypothesis

Am J Med Genet. 1993 Apr 15;46(2):182-4. doi: 10.1002/ajmg.1320460217.


Von Recklinghausen neurofibromatosis or neurofibromatosis type I (NF1) is a relatively frequent (1/3,000 livebirths) autosomal dominant condition. Some unusual aspects are noted in this disorder: new mutations are frequent and almost all are of paternal origin without parental age effect. The recurrence of NF1 among children of healthy parents is rare as opposed to other dominant disorders. I propose that in NF1 (1) new mutations occur often in somatic cells or in late germinal cells, however, they occur very rarely in early germinal cells leading to germinal mosaicism and (2) the individual with somatic mosaicism presents symptoms of the disease. Therefore, an NF1 patient with an apparent new mutation is often a somatic mosaic for the mutation and if the mosaic is also present in germinal cells some of his children will be affected. This hypothesis may explain the unusual aspects of mutation in NF1.

Publication types

  • Review

MeSH terms

  • Female
  • Genes, Neurofibromatosis 1
  • Humans
  • Infant, Newborn
  • Male
  • Models, Genetic
  • Mosaicism
  • Mutation
  • Neurofibromatosis 1 / genetics*