A novel two-base mutation in the [formula omitted] superoxide dismutase gene associated with familial amyotrophic lateral sclerosis in Japan

Abstract

We have identified a novel two-base mutation in exon 1 of the Cu Zn superoxide dismutase (SOD1) gene (T GC to T TT ), 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 β-strand of the SOD1, a family with a mutation of Val 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.