SOD1 MISSENSE MUTATION IN AN ITALIAN FAMILY WITH ALS

We have discovered a new Italian pedigree with autosomal-dominant ALS. The pedigree, at present, comprises 75 members distributed in five ge nerations. ALS was diagnosed in eight patients. The mean +/- SD age of onset of the disease was 46.8 +/- 13.5 years, with a range of 29 to 6 3 years. The mean +/- SD duration of the disease was 11.6 +/- 1.7 mont hs. Molecular genetic studies showed a missense mutation (Gly-->Ser, c odon 41) in exon 2 of the Cu/Zn superoxide dismutase gene (SOD1) on ch romosome 21 in the available affected member and in 45% of the at-risk subjects of the pedigree. This study confirms the presence of SOD1 po int mutations in families with autosomal-dominant ALS and suggests tha t additional genetic or environmental factors may be involved in the f ull expression of the disease.