Article Text

other Versions

PDF
Mosaicism in NF2 an update of risk based on uni/bilaterality of vestibular schwannoma at presentation and sensitive mutation analysis including MLPA
  1. D Gareth Evans (gareth.evans{at}cmmc.nhs.uk)
  1. St Mary's Hospital, Manchester, United Kingdom
    1. Richard Ramsden (richard.ramsden{at}cmmc.nhs.uk)
    1. Manchester Royal, United Kingdom
      1. andrew shenton (andrew.shenton{at}cmmc.nhs.uk)
      1. St Mary's Hospital, Manchester, United Kingdom
        1. Carolyn Gokhale (corolyn.gokhale{at}cmmc.nhs.uk)
        1. St Mary's Hospital, Manchester, United Kingdom
          1. naomi L bowers (naomi.bowers{at}cmmc.nhs.uk)
          1. St Mary's Hospital, Manchester, United Kingdom
            1. susan M Huson (smhuson{at}aol.com)
            1. St Mary's Hospital, Manchester, United Kingdom
              1. Gabi Pichert
              1. Guys Hospital, United Kingdom
                1. andrew Wallace (andrew.wallace{at}cmmc.nhs.uk)
                1. St Mary's Hospital, Manchester, United Kingdom

                  Abstract

                  Background: NF2 is almost unique amongst 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: We have analysed our expanded database of 460 NF2 families and 704 affected individuals for mosaicism and transmission risks to offspring.

                  Results: we have identified 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. Offspring risks can be radically reduced on the basis of a sensitive mutation analysis of blood DNA including MLPA (detects 15% of all mutations), but MLPA is not able to detect even high levels of mosaicism.

                  Discussion:< We have further delineated the chances of mosaicism in NF2 and resultant risks of mutation transmission to offspring in a number of different clinical situations. We also report for the first time the use of MLPA in our large NF2 series.

                  • MLPA
                  • NF2
                  • exon deletion
                  • mosaic
                  • offspring risk

                  Statistics from Altmetric.com

                  Request permissions

                  If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.