Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Paternal origin of new mutations in Von Recklinghausen neurofibromatosis

Abstract

VON Recklinghausen neurofibromatosis (NF-1)1–4 is a common autosomal dominant disorder. The estimated new mutation rate (1 x 10−4) is one of the highest for a human disorder1. Here we report that in 12 of 14 families we have analysed, the new mutation is of paternal origin. This result is similar to that recently obtained for retinoblastoma5,6. In other genetic disorders that show a bias towards paternal origin of new mutations, there is a marked increase in the incidence of mutations with paternal age7, consistent with the mutations arising from replication errors in mitosis of spermatogonial stem cells. In retinoblastoma and NF-1, however, such paternal age effects are slight or absent3,7,8. The mechanism or timing of germline mutation could therefore be different in the two cases.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Huson, S. M., Compston, D. A. S., Clark, P. & Harper, P. S. J. med. Genet. 26, 704–711 (1989).

    Article  CAS  Google Scholar 

  2. Huson, S. M., Harper, P. S. & Compston, D. A. S. Brain 111, 1355–1381 (1988).

    Article  Google Scholar 

  3. Riccardi, V. M. & Eichner, J. E. Neurofibromatosis (Johns Hopkins University Press, Baltimore and London, 1986).

    Google Scholar 

  4. Collins, F. S., Ponder, B. A. J., Seizinger, B. R. & Epstein, C. J. Trends Genet. 5, 217–221 (1989).

    Article  CAS  Google Scholar 

  5. Dryja, T. et al. Nature 339, 556–558 (1989).

    Article  ADS  CAS  Google Scholar 

  6. Zhu, X. et al. Nature 340, 312–313 (1989).

    Article  ADS  CAS  Google Scholar 

  7. Vogel, F. & Motulsky, A. G. Human Genetics 2nd Edn (Springer, Berlin, 1986).

    Book  Google Scholar 

  8. Riccardi, V. M., Dobson, C. E., Chakraborty, R. & Bontke, C. Am. J. med. Genet. 18, 169–176 (1984).

    Article  CAS  Google Scholar 

  9. Winter, R. M. & Pembrey, M. E. Am. J. med. Genet. 12, 437–441 (1982).

    Article  CAS  Google Scholar 

  10. Fain, P. M. et al. Am. J. hum. Genet. 45, 721–728 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Wolff, R. K., Plaetke, R., Jeffreys, A. J. & White, R. Genomics 5, 382–384 (1989).

    Article  CAS  Google Scholar 

  12. Reik, W. & Surani, M. A. Nature 338, 112–113 (1989).

    Article  ADS  CAS  Google Scholar 

  13. Stumpf, D. A. et al. Neurofibromatosis Vol. 6, No. 12 (NIH Consensus Development Conferences Statement, 1987).

    Google Scholar 

  14. O'Connell, P. et al. Am. J. hum. Genet. 44, 51–57 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Wong, Z., Wilson, V., Jeffreys, A. J. & Thein, S. L. Nucleic Acids Res. 14, 4605–4616 (1986).

    Article  CAS  Google Scholar 

  16. Wong, Z., Wilson, V., Patel, I., Povey, S. & Jeffreys, A. J. Ann. hum. Genet. 51, 269–288 (1987).

    Article  CAS  Google Scholar 

  17. Jeffreys, A. J., Wilson, V. & Thein, S. L. Nature 314, 67 (1985).

    Article  ADS  CAS  Google Scholar 

  18. Fraser, N. J., Boyd, Y., Brownlee, G. G. & Craig, I. W. Nucleic Acids Res. 15, 9616 (1987).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jadayel, D., Fain, P., Upadhyaya, M. et al. Paternal origin of new mutations in Von Recklinghausen neurofibromatosis. Nature 343, 558–559 (1990). https://doi.org/10.1038/343558a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/343558a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing