title: Pathogenesis of vestibular schwannoma in ring chromosome 22.
abstract: BACKGROUND
  Ring chromosome 22 is a rare human constitutional cytogenetic abnormality. Clinical features of neurofibromatosis type 1 and 2 as well as different tumour types have been reported in patients with ring chromosome 22. The pathogenesis of these tumours is not always clear yet.
  
  
  METHODS
  We report on a female patient with a ring chromosome 22 presenting with severe mental retardation, autistic behaviour, café-au-lait macules and facial dysmorphism. Peripheral blood lymphocytes were karyotyped and array CGH was performed on extracted DNA. At the age of 20 years she was diagnosed with a unilateral vestibular schwannoma. Tumour cells were analyzed by karyotyping, array CGH and NF2 mutation analysis.
  
  
  RESULTS
  Karyotype on peripheral blood lymphocytes revealed a ring chromosome 22 in all analyzed cells. A 1 Mb array CGH experiment on peripheral blood DNA showed a deletion of 5 terminal clones on the long arm of chromosome 22. Genetic analysis of vestibular schwannoma tissue revealed loss of the ring chromosome 22 and a somatic second hit in the NF2 gene on the remaining chromosome 22.
  
  
  CONCLUSIONS
  We conclude that tumours can arise by the combination of loss of the ring chromosome and a pathogenic NF2 mutation on the remaining chromosome 22 in patients with ring chromosome 22. Our findings indicate that patients with a ring 22 should be monitored for NF2-related tumours starting in adolescence.
authors.affiliation: Department of human genetics, University Hospital Gasthuisberg, Leuven, Belgium. Ellen.Denayer@med.kuleuven.be
authors.forename: Ellen
authors.initials: E
authors.lastname: Denayer
authors.forename: Hilde
authors.initials: H
authors.lastname: Brems
authors.forename: Paul
authors.initials: P
authors.lastname: de Cock
authors.forename: Gareth D
authors.initials: GD
authors.lastname: Evans
authors.forename: Frank
authors.initials: F
authors.lastname: Van Calenbergh
authors.forename: Naomi
authors.initials: N
authors.lastname: Bowers
authors.forename: Raf
authors.initials: R
authors.lastname: Sciot
authors.forename: Maria
authors.initials: M
authors.lastname: Debiec-Rychter
authors.forename: Joris V
authors.initials: JV
authors.lastname: Vermeesch
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fryns
authors.forename: Eric
authors.initials: E
authors.lastname: Legius
mesh_terms: D000328:Adult; D002892:Chromosomes, Human, Pair 22; D005260:Female; D016514:Genes, Neurofibromatosis 1; D016515:Genes, Neurofibromatosis 2; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008279:Magnetic Resonance Imaging; D009154:Mutation; D009464:Neuroma, Acoustic / Q000175:diagnosis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012303:Ring Chromosomes; D017422:Sequence Analysis, DNA