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 Cys(6) 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 Ala(4) to Val, Ala(4) to Thr and Val(14) to Met, affected members of the present family showed a rapid progression of motor dysfunction. Although Ala(4), Cys(6) and Val(7) reside in the middle of the first beta-strand of the SOD1, a family with a mutation of Va1(7) 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.