title: Cranial meningiomas in 411 neurofibromatosis type 2 (NF2) patients with proven gene mutations: clear positional effect of mutations, but absence of female severity effect on age at onset.
abstract: BACKGROUND
  Meningiomas have been reported to occur in approximately 50% of neurofibromatosis type 2 (NF2) patients. The NF2 gene is commonly biallelically inactivated in both schwannomas and meningiomas. The spectrum of NF2 mutations consists mainly of truncating (nonsense and frameshift) mutations. A smaller number of patients have missense mutations, which are associated with a milder disease phenotype.
  
  
  METHODS
  This study analysed the cumulative incidence and gender effects as well as the genotype-phenotype correlation between the position of the NF2 mutation and the occurrence of cranial meningiomas in a cohort of 411 NF2 patients with proven NF2 mutations.
  
  
  CONCLUSIONS
  Patients with mutations in exon 14 or 15 were least likely to develop meningiomas. Cumulative risk of cranial meningioma to age 50 years was 70% for exons 1-3, 81% for exons 4-6, 49% for exons 7-9, 56% for exons 10-13, and 28% for exons 14-15. In the cohort of 411 patients, no overall gender bias was found for occurrence of meningioma in NF2 disease. Cumulative incidence of meningioma was close to 80% by 70 years of age for both males and females, but incidence by age 20 years was slightly increased in males (male 25%, female 18%; p=0.023). Conversely, an increased risk of meningiomas in women with mosaic NF2 disease was also found.
authors.affiliation: Department of Genetic Medicine, St Mary's Hospital, Manchester Academic Health Sciences Center, University of Manchester, Oxford Road, Manchester M13 9WL, UK.
authors.forename: Miriam J
authors.initials: MJ
authors.lastname: Smith
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Higgs
authors.forename: Naomi L
authors.initials: NL
authors.lastname: Bowers
authors.forename: Dorothy
authors.initials: D
authors.lastname: Halliday
authors.forename: Joan
authors.initials: J
authors.lastname: Paterson
authors.forename: James
authors.initials: J
authors.lastname: Gillespie
authors.forename: Susan M
authors.initials: SM
authors.lastname: Huson
authors.forename: Simon R
authors.initials: SR
authors.lastname: Freeman
authors.forename: Simon
authors.initials: S
authors.lastname: Lloyd
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rutherford
authors.forename: Andrew T
authors.initials: AT
authors.lastname: King
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wallace
authors.forename: Richard T
authors.initials: RT
authors.lastname: Ramsden
authors.forename: D Gareth R
authors.initials: DG
authors.lastname: Evans
mesh_terms: D015331:Cohort Studies; D005091:Exons; D005260:Female; D016515:Genes, Neurofibromatosis 2; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008579:Meningioma / Q000150:complications / Q000235:genetics* / Q000473:pathology; D009030:Mosaicism; D009154:Mutation; D016518:Neurofibromatosis 2 / Q000150:complications / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors