Molecular analysis of the NF2 tumor-suppressor gene in schwannomatosis

Am J Hum Genet. 1997 Dec;61(6):1293-302. doi: 10.1086/301633.


Patients with multiple schwannomas without vestibular schwannomas have been postulated to compose a distinct subclass of neurofibromatosis (NF), termed "schwannomatosis." To compare the molecular-genetic basis of schwannomatosis with NF2, we examined the NF2 locus in 20 unrelated schwannomatosis patients and their affected relatives. Tumors from these patients frequently harbored typical truncating mutations of the NF2 gene and loss of heterozygosity of the surrounding region of chromosome 22. Surprisingly, unlike patients with NF2, no heterozygous NF2-gene changes were seen in normal tissues. Examination of multiple tumors from the same patient revealed that some schwannomatosis patients are somatic mosaics for NF2-gene changes. By contrast, other individuals, particularly those with a positive family history, appear to have an inherited predisposition to formation of tumors that carry somatic alterations of the NF2 gene. Further work is needed to define the pathogenetics of this unusual disease mechanism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cohort Studies
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Female
  • Frameshift Mutation
  • Genes, Neurofibromatosis 2*
  • Haplotypes / genetics
  • Humans
  • Loss of Heterozygosity
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Mosaicism
  • Neurilemmoma / classification
  • Neurilemmoma / genetics*
  • Neurofibromatoses / classification
  • Neurofibromatoses / genetics*
  • Pedigree
  • Point Mutation
  • Spinal Neoplasms / genetics


  • DNA, Neoplasm