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.
Morita
M
M
Department of Neurology, Tohoku University School of Medicine, Japan.
Aoki
M
M
Abe
K
K
Hasegawa
T
T
Sakuma
R
R
Onodera
Y
Y
Ichikawa
N
N
Nishizawa
M
M
Itoyama
Y
Y
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