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

Nat Genet. 1995 May;10(1):61-6. doi: 10.1038/ng0595-61.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / genetics*
  • Base Sequence
  • Erythrocytes / metabolism
  • Exons
  • Female
  • Homozygote*
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Polymorphism, Single-Stranded Conformational
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase / metabolism


  • Superoxide Dismutase