title: Amyotrophic lateral sclerosis associated with homozygosity for an Asp90Ala mutation in CuZn-superoxide dismutase.
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.
authors.affiliation: Department of Neurology, Umeå University Hospital, Sweden.
authors.forename: P M
authors.initials: PM
authors.lastname: Andersen
authors.forename: P
authors.initials: P
authors.lastname: Nilsson
authors.forename: V
authors.initials: V
authors.lastname: Ala-Hurula
authors.forename: M L
authors.initials: ML
authors.lastname: Keränen
authors.forename: I
authors.initials: I
authors.lastname: Tarvainen
authors.forename: T
authors.initials: T
authors.lastname: Haltia
authors.forename: L
authors.initials: L
authors.lastname: Nilsson
authors.forename: M
authors.initials: M
authors.lastname: Binzer
authors.forename: L
authors.initials: L
authors.lastname: Forsgren
authors.forename: S L
authors.initials: SL
authors.lastname: Marklund
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D001483:Base Sequence; D004912:Erythrocytes / Q000378:metabolism; D005091:Exons; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
chemical_list: D013482:Superoxide Dismutase