title: Familial schwannomatosis: exclusion of the NF2 locus as the germline event.
abstract: BACKGROUND
  Schwannomatosis is a recently recognized disorder, defined as multiple pathologically proven schwannomas without vestibular tumors diagnostic of neurofibromatosis 2 (NF2). Some investigators have questioned whether schwannomatosis is merely an attenuated form of NF2.
  
  
  METHODS
  The authors identified eight families in which a proband met their diagnostic criteria for schwannomatosis. Archived and prospectively acquired tumor specimens were studied by mutational analysis at the NF2 locus, loss of heterozygosity analysis along chromosome 22, and fluorescent in situ hybridization analysis of NF2 and the more centromeric probe BCR. Linkage analysis could be performed in six of eight families.
  
  
  RESULTS
  Clinical characterization of these kindreds showed that no affected family member harbored a vestibular tumor. Molecular analysis of 28 tumor specimens from 17 affected individuals in these kindreds revealed a pattern of somatic NF2 inactivation incompatible with our current understanding of NF2 as an inherited tumor suppressor gene syndrome. Linkage analysis excluded the NF2 locus in two kindreds, and showed a maximum lod score of 6.60 near the more centromeric marker D22S1174.
  
  
  CONCLUSIONS
  Schwannomatosis shows clinical and molecular differences from NF2 and should be considered a third major form of neurofibromatosis. Further work is needed to identify the inherited genetic element responsible for familial schwannomatosis.
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Charlestown, USA. maccollin@helix.mgh.harvard.edu
authors.forename: M
authors.initials: M
authors.lastname: MacCollin
authors.forename: C
authors.initials: C
authors.lastname: Willett
authors.forename: B
authors.initials: B
authors.lastname: Heinrich
authors.forename: L B
authors.initials: LB
authors.lastname: Jacoby
authors.forename: J S
authors.initials: JS
authors.lastname: Acierno
authors.forename: A
authors.initials: A
authors.lastname: Perry
authors.forename: D N
authors.initials: DN
authors.lastname: Louis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D016515:Genes, Neurofibromatosis 2; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D009442:Neurilemmoma / Q000235:genetics*; D017253:Neurofibromatoses / Q000145:classification* / Q000235:genetics; D010375:Pedigree