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

J Med Genet. 2007 Jul;44(7):424-8. doi: 10.1136/jmg.2006.047753. Epub 2007 Feb 16.


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.

Publication types

  • Comparative Study

MeSH terms

  • DNA Mutational Analysis
  • Genetic Predisposition to Disease*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Molecular Probe Techniques
  • Mosaicism*
  • Neurofibromatosis 2 / complications*
  • Neurofibromatosis 2 / genetics*
  • Neuroma, Acoustic / etiology*
  • Nucleic Acid Amplification Techniques
  • Pedigree
  • Polymorphism, Single-Stranded Conformational
  • Risk Assessment