AMYOTROPHIC-LATERAL-SCLEROSIS ASSOCIATED WITH HOMOZYGOSITY FOR AN ASP90ALA MUTATION IN CUZN-SUPEROXIDE DISMUTASE

Recent reports have shown heterozygosity for some twenty different mut ations in the CuZn-superoxide dismutase (CuZn-SOD) gene in familial am yotrophic lateral sclerosis (FALS), and analysed samples from patients have shown decreased enzymic activity. Here we report homozygosity fo r an exon 4 mutation, Asp90Ala in fourteen patients among four unrelat ed ALS families and four apparently sporadic ALS patients from Sweden and Finland. The erythrocyte CuZn-SOD activity is essentially normal. Our findings suggest that this CuZn-SOD mutation causes ALS by a gain of function rather than by loss, and that the Asp90Ala mutation is les s detrimental than previously reported mutations.