Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy (original) (raw)

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.

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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
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  2. Elizabeth M Wilson
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  3. Dennis B Lubahn
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  4. A. E Harding
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  5. Kenneth H Fischbeck
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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

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