Superoxide dismutase gene mutations in Italian patients with familial and sporadic amyotrophic lateral sclerosis: identification of three novel missense mutations

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative diso rder affecting motor neurons. The majority of the patients are sporadic cas es (SALS), while 5-10% of the patients have a family history of ALS (famili al ALS or FALS). Mutations in the gene coding for cytoplasmic Cu/Zn superox ide dismutase (SOD1) have been identified in about 20% of FALS cases. We fo und SOD1-gene mutations in five of 34 unrelated FALS. and in two of 44 SALS patients. Three FALS patients carried the previously described A4V (two ca ses) and L84F mutations (one case), while two FALS patients carried new mis sense mutations: a G12R substitution in exon 1, and a F45C substitution in exon 2. respectively. The newly identified mutations were both associated w ith a slowly progressive disease course. Two SALS patients carried the homo zygous D90A and the heterozygous I113T mutation. respectively. In addition. in one SALS patient we identified an A95T amino acid substitution. that is apparently a non-pathogenic SOD1 variant. Our study increases the number o f ALS-associated SOD1 gene mutations. (C) 2001 Elsevier Science B.V. All ri ghts reserved.