Identification of six novel SOD1 gene mutations in familial amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the premature death of motor neurons. In approximately 10% of the cases the disease is inherited as autosomal dominant trait (FALS). It has been found that mutations in the Cu/Zn superoxide dismutase gene (SOD1) are responsible for approximately 15% of FALS kindreds. We screened affected individuals from 70 unrelated FALS kindreds and identified 10 mutations, 6 of which are novel. Surprisingly, we have found a mutation in exon 3, which includes most of the active site loop and Zn2+ binding sites, a region where no previous SOD1 mutations have been found. Our data increase the number of different SOD1 mutations causing FALS to 55, a significant fraction of the 154 amino acids of this relatively small protein.
Boukaftane
Y
Y
Centre for Research in Neuroscience, McGill University, Montreal, Canada.
Khoris
J
J
Moulard
B
B
Salachas
F
F
Meininger
V
V
Malafosse
A
A
Camu
W
W
Rouleau
G A
GA
D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D017931:DNA Primers; D005799:Genes, Dominant; D005820:Genetic Testing; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology*; D016133:Polymerase Chain Reaction; D013045:Species Specificity; D013482:Superoxide Dismutase / Q000235:genetics*
D017931:DNA Primers; D004247:DNA; D013482:Superoxide Dismutase