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Amyotrophic lateral sclerosis associated with homozygosity for an Asp90Ala mutation in CuZn-superoxide dismutase

Nature Genetics volume 10, pages 61–66 (1995)Cite this article

Abstract

Recent reports have shown heterozygosity for some twenty different mutations in the CuZn–superoxide dismutase (CuZn–SOD) gene in familial amyotrophic lateral sclerosis (FALS), and analysed samples from patients have shown decreased enzymic activity. Here we report homozygosity for an exon 4 mutation, Asp90Ala in fourteen patients among four unrelated ALS families and four apparently sporadic ALS patients from Sweden and Finland. The erythrocyte CuZn–SOD activity is essentially normal. Our findings suggest that this CuZn–SOD mutation causes ALS by a gain of function rather than by loss, and that the Asp90Ala mutation is less detrimental than previously reported mutations.

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Authors and Affiliations

  1. Departments of Neurology, Umeå, University Hospital, Umeå, S-901 85, Sweden

    Peter M. Andersen, Michael Binzer & Lars Forsgren

  2. Clinical Chemistry, Umeå, University Hospital, Umeå, S-901 85, Sweden

    Peter Nilsson, Lotta Nilsson & Stefan L. Marklund

  3. Department of Neurology, Centrallasarettet Kemi, Kemi, SF-941 00, Finland

    Veli Ala-Hurula

  4. Department of Neurology, Lapin Keskussairaala, Rovaniemi, SF-961 01, Finland

    Marja-Leena Keränen

  5. Department of Neurology, Mikkelin Keskussairaala, Mikkeli, SF-501 00, Finland

    Ilkka Tarvainen

  6. Kauniala Sjukhus för krigsinvalider, Kauniainen, SF-02700, Finland

    Tuula Haltia

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  1. Peter M. Andersen
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Andersen, P., Nilsson, P., Ala-Hurula, V. et al. Amyotrophic lateral sclerosis associated with homozygosity for an Asp90Ala mutation in CuZn-superoxide dismutase. Nat Genet 10, 61–66 (1995). https://doi.org/10.1038/ng0595-61

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