A novel two-base mutation in the Cu/Zn superoxide dismutase gene associated with familial amyotrophic lateral sclerosis in Japan.
We have identified a novel two-base mutation in exon 1 of the Cu/Zn superoxide dismutase (SOD1) gene (TGC to TTT), which resulted in Cys6 to Phe substitution in a Japanese family with amyotrophic lateral sclerosis (ALS). This is the first case of familial ALS-associated two-base change of the SOD1 gene. Similar to several mutations in exon 1 of the SOD1 gene such as Ala4 to Val, Ala4 to Thr and Val14 to Met, affected members of the present family showed a rapid progression of motor dysfunction. Although Ala4, Cys6 and Val7 reside in the middle of the first beta-strand of the SOD1, a family with a mutation of Val7 to Glu associates with slow progression of the disease. These findings suggest that clinical courses are variable with each mutation, even in the same exon.
Department of Neurology, Tohoku University School of Medicine, Japan.
M
M
Morita
M
M
Aoki
K
K
Abe
T
T
Hasegawa
R
R
Sakuma
Y
Y
Onodera
N
N
Ichikawa
M
M
Nishizawa
Y
Y
Itoyama
D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D001483:Base Sequence; D005091:Exons / Q000235:genetics; D005192:Family Health; D006801:Humans; D007564:Japan; D007962:Leukocytes / Q000502:physiology; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000502:physiology; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D013482:Superoxide Dismutase / Q000235:genetics*
D013482:Superoxide Dismutase