Identification of new mutations in the Cu/Zn superoxide dismutase gene of patients with familial amyotrophic lateral sclerosis.
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.
Pramatarova
A
A
Centre for Research in Neuroscience, McGill University, Montreal.
Figlewicz
D A
DA
Krizus
A
A
Han
F Y
FY
Ceballos-Picot
I
I
Nicole
A
A
Dib
M
M
Meininger
V
V
Brown
R H
RH
Rouleau
G A
GA
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
D003300:Copper; D004247:DNA; D013482:Superoxide Dismutase; D015032:Zinc