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Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis

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A Corrigendum to this article was published on 22 July 1993

Abstract

AMYOTROPHIC lateral sclerosis (ALS) is a degenerative disorder of motor neurons in the cortex, brainstem and spinal cord1,2. Its cause is unknown and it is uniformly fatal, typically within five years3. About 10% of cases are inherited as an autosomal dominant trait, with high penetrance after the sixth decade4,5. In most instances, sporadic and autosomal dominant familial ALS (FALS) are clinically similar4,6,7. We have previously shown that in some but not all FALS pedigrees the disease is linked to a genetic defect on chromosome 21q (refs 8,9). Here we report tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O–2 to O2 and H2O2 (ref. 10). Given this linkage and the potential role of free radical toxicity in other neurodenegerative disorders11, we investigated SOD1 as a candidate gene in FALS. We identified 11 different SOD1 missense mutations in 13 different FALS families.

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Author notes

  1. Robert H. Brown: To whom correspondence should be addressed.

Authors and Affiliations

  1. Day Neuromuscular Research Laboratory, Massachusetts General Hospital, Room 6627, MGH-East, Building 149,13th Street, Charlestown, Massachusetts, 02129, USA

    Daniel R. Rosen, Peter Sapp, Jeremiah P. O'Regan, Diane McKenna-Yasek, Sandra M. Gaston & Robert H. Brown Jr

  2. Department of Neurology, Northwestern University Medical School, Chicago, Illinois, 60611, USA

    Teepu Siddique, Afif Hentati, Han-Xiang Deng, Annarueber Cayabyab, Brian Herzfeldt, Wu-Yen Hung, Gang Deng, Celestine Smyth & Edwin Soriano

  3. Eleanor Roosevelt Institute for Cancer Research and the University of Colorado Health Science Center, Denver, Colorado, 80206, USA

    David Patterson, Deirdre Donaldson, Zohra Rahmani & Ralph Berger

  4. Center for Research in Neuroscience, McGill University,

    Denise A. Figlewicz, Jun Goto, Aldis Krizus & Guy A. Rouleau

  5. the Montreal General Hospital Research Institute, Montreal, PQ H3G1A4, Canada

    Denise A. Figlewicz, Jun Goto, Aldis Krizus & Guy A. Rouleau

  6. Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Boston, Massachusetts, 02139, USA

    Peter Sapp, Jeremiah P. O'Regan & H. Robert Horvitz

  7. Laboratory of Genetics and Aging, Neuroscience Center, Massachusetts General Hospital, Boston, Massachusetts, 02129, USA

    Sandra M. Gaston & Rudolph E. Tanzi

  8. Department of Neurology, Northshore University Hospital, Manhasset, New York, 11030, USA

    John J. Halperin

  9. Department of Neurology, Universitaire Ziekenhuizen, Leuven, 3000, Belgium

    Raymond Van den Bergh

  10. Department of Neurology, University of Washington School of Medicine, Seattle, Washington, 98195, USA

    Thomas Bird

  11. Department of Neurology, Mayo Clinic, Rochester, Minnesota, 55905, USA

    Donald W. Mulder

  12. Australian Neuromuscular Research Institute, Nedlands, Western Australia, Australia

    Nigel G. Laing

  13. Department of Medicine (Neurology), Duke University Medical Center, Durham, North Carolina, 27710, USA

    Margaret A. Pericak–Vance

  14. Molecular Neurogenetics Laboratory, Neuroscience Center, Massachusetts General Hospital, Boston, Massachusetts, 02129, USA

    Jonathan Haines & James S. Gusella

Authors
  1. Daniel R. Rosen
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  2. Teepu Siddique
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  4. Denise A. Figlewicz
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  23. Gang Deng
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  29. Jonathan Haines
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  30. Guy A. Rouleau
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  32. H. Robert Horvitz
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  33. Robert H. Brown Jr
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Rosen, D., Siddique, T., Patterson, D. et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362, 59–62 (1993). https://doi.org/10.1038/362059a0

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