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.

Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy

Nature volume 352, pages 77–79 (1991)Cite this article

Abstract

X-LINKED spinal and bulbar muscular atrophy (Kennedy's disease) is an adult-onset form of motorneuron disease which may be associated with signs of androgen insensitivity. We have now investigated whether the androgen receptor gene on the proximal long arm of the X chromosome is a candidate gene for this disease. In patient samples we found androgen receptor gene mutations with increased size of a polymorphic tandem CAG repeat in the coding region. These amplified repeats were absolutely associated with the disease, being present in 35 unrelated patients and none of 75 controls. They segregated with the disease in 15 families, with no recombination in 61 meioses (the maximum log likelihood ratio (lod score) is 13.2 at a recombination rate of 0). The association is unlikely to be due to linkage disequilibrium, because 11 different disease alleles were observed. We conclude that enlargement of the CAG repeat in the androgen receptor gene is probably the cause of this disorder.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

References

  1. Harding, A. E. et al. J. Neurol. Neurosurg. Psychiatry 45, 1012–1019 (1982).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. Arbizu, T. et al. J. Neurol. Sci. 59, 371–382 (1983).

    CAS  Article  PubMed  Google Scholar 

  3. Warner, C. L. et al. Neurology 41 (Suppl. 1), 313 (1991).

    Article  Google Scholar 

  4. Brown, C. J. et al. Am. J. hum. Genet. 44, 264–269 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Fischbeck, K. H. et al. Neurology 36, 1595–1598 (1986).

    CAS  Article  PubMed  Google Scholar 

  6. Fischbeck, K. H., Souders, D. & La Spada, A. Adv. Neurol. 56, 209–213 (1991).

    CAS  PubMed  Google Scholar 

  7. Edwards, A., Hammond, H. A., Caskey, C. T. & Chakraborty, R. Geonomics (submitted).

  8. Lubahn, D. B. et al. Molec. Endocrinol. 2, 1265–1275 (1988).

    CAS  Article  Google Scholar 

  9. Tilley, W. D. et al. Proc. natn. Acad. Sci. U.S.A. 86, 327–331 (1989).

    ADS  CAS  Article  Google Scholar 

  10. Ott, J. Am. J. hum. Genet. 26, 588–597 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Tan, J. et al. Molec. Endrocrinol. 2, 1276–1285 (1988).

    CAS  Article  Google Scholar 

  12. Wharton, K. A., Yedvobnick, B., Finnerty, V. G. & Artavanis-Tsakonas, S. Cell. 40, 55–62 (1985).

    CAS  Article  PubMed  Google Scholar 

  13. Duboule, D., Haenlin, M., Galliot, B. & Mohier, E. Molec. cell. Biol. 7, 2003–2006 (1987).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. Mitchell, P. J. & Tjian, R. Science 245, 371–378 (1989).

    ADS  CAS  Article  PubMed  Google Scholar 

  15. Kao, C. C. et al. Science 248, 1646–1649 (1990).

    ADS  CAS  Article  PubMed  Google Scholar 

  16. Sar, M. & Stumpf, W. E. Science 197, 77–80 (1977).

    ADS  CAS  Article  PubMed  Google Scholar 

  17. Kurz, E. M., Sengelaub, D. R. & Arnold, A. P. Science 232, 395–398 (1986).

    ADS  CAS  Article  PubMed  Google Scholar 

  18. Yu, W. A. J. Neurosci. 9, 3908–3914 (1989).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Yandell, D. W. & Dryja, T. P. Am. J. hum. Genet. 45, 547–555 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neurology Department University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104-6146, USA

    Albert R. La Spada & Kenneth H Fischbeck

  2. Laboratories for Reproductive Biology, University of North Carolina, Chapel Hill, North Carolina, 27599, USA

    Elizabeth M Wilson & Dennis B Lubahn

  3. Institute of Neurology, The National Hospital, Queen Square, London, WC1N 3BG, UK

    A. E Harding

Authors
  1. Albert R. La Spada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elizabeth M Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dennis B Lubahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. E Harding
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kenneth H Fischbeck
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Spada, A., Wilson, E., Lubahn, D. et al. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352, 77–79 (1991). https://doi.org/10.1038/352077a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/352077a0

Further reading

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

Advanced 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