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Mosaicism in neurofibromatosis type 2: an update of risk based on uni/bilaterality of vestibular schwannoma at presentation and sensitive mutation analysis including multiple ligation-dependent probe amplification
  1. D Gareth R Evans1,
  2. R T Ramsden1,
  3. A Shenton1,
  4. C Gokhale1,
  5. N L Bowers1,
  6. S M Huson1,
  7. G Pichert2,
  8. A Wallace1
  1. 1Academic Unit of Medical Genetics and Regional Genetics Service, St Mary’s Hospital, Manchester, UK
  2. 2Genetics Centre, Guys Hospital, London, UK
  1. Correspondence to:
 Professor D G R Evans
 Department of Medical Genetics, St Mary’s Hospital, Hathersage Road, Manchester M13 0JH, UK;gareth.evans{at}


Background: Neurofibromatosis type 2 (NF2) is almost unique among inherited disorders in the frequency of mosaicism in the first affected generation. However, the implications of this on transmission risks have not been fully elucidated.

Methods: The expanded database of 460 families with NF2 and 704 affected individuals was analysed for mosaicism and transmission risks to offspring.

Results: 64 mosaic patients, with a projected mosaicism rate of 33% for sporadic classical NF2 with bilateral vestibular schwannoma at presentation and 60% for those presenting unilaterally, were identified. Offspring risks can be radically reduced on the basis of a sensitive mutation analysis of blood DNA including multiple ligation-dependent probe amplification (MLPA, which detects 15% of all mutations), but even MLPA cannot detect high levels of mosaicism.

Conclusion: The chances of mosaicism in NF2 and the resultant risks of transmission of the mutation to offspring in a number of different clinical situations have been further delineated. The use of MLPA in this large NF2 series is also reported for the first time.

  • FISH, fluorescence in situ hybridisation
  • MLPA, multiple ligation-dependent probe amplification
  • NF2, neurofibromatosis type 2
  • UVS, unilateral vestibular schwannoma
  • VS, vestibular schwannoma

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  • Published Online First 16 February 2007

  • Competing interests: None declared.