title: Identification of new mutations in the Cu/Zn superoxide dismutase gene of patients with familial amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting motor neurons. Although most cases of ALS are sporadic, approximately 10% are inherited as an autosomal dominant trait. Mutations in the Cu/Zn superoxide dismutase gene (SOD 1) are responsible for a fraction of familial ALS (FALS). Screening our FALS kindreds by SSCP, we have identified mutations in 15 families, of which 9 have not been previously reported. Two of the new mutations alter amino acids that have never been implicated in FALS. One of them affects a highly conserved amino acid involved in dimer contact, and the other one affects the active-site loop of the enzyme. These two mutations reduce significantly SOD 1 enzyme activity in lymphoblasts. Our results suggest that SOD 1 mutations are responsible for > or = 13% of FALS cases.
authors.affiliation: Centre for Research in Neuroscience, McGill University, Montreal.
authors.forename: A
authors.initials: A
authors.lastname: Pramatarova
authors.forename: D A
authors.initials: DA
authors.lastname: Figlewicz
authors.forename: A
authors.initials: A
authors.lastname: Krizus
authors.forename: F Y
authors.initials: FY
authors.lastname: Han
authors.forename: I
authors.initials: I
authors.lastname: Ceballos-Picot
authors.forename: A
authors.initials: A
authors.lastname: Nicole
authors.forename: M
authors.initials: M
authors.lastname: Dib
authors.forename: V
authors.initials: V
authors.lastname: Meininger
authors.forename: R H
authors.initials: RH
authors.lastname: Brown
authors.forename: G A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D001483:Base Sequence; D003300:Copper; D004247:DNA / Q000032:analysis; D005091:Exons; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D013482:Superoxide Dismutase / Q000235:genetics*; D015032:Zinc
chemical_list: D003300:Copper; D004247:DNA; D013482:Superoxide Dismutase; D015032:Zinc