Introduction: Familial amyotrophic lateral sclerosis (FALS) is recognised as a heterogeneous syndrome with mutations in the Cu/Zn superoxide dismutase (SOD1) gene being the most frequently identified cause of ALS. Interfamily and intrafamily phenotypic variability have been associated with some SOD1 mutations but not with other mutations.1 2 We prospectively screened sporadic ALS and FALS patients from Switzerland for SOD1 mutations and followed their clinical course.
Methods: With written informed consent and approval by the local ethical review boards, blood was drawn from 257 patients and from 245 Swiss blood donors matched for ethnicity, age and gender. Forty-seven of the patients had one or more affected blood relatives within three generations and were classified as FALS. SOD1 analysis was performed in Sweden as described.1
Results: Nine patients from seven unrelated families carried a SOD1 mutation (table 1), including three novel mutations (V5L, L144F (TTG→TTT) and E78insSI (c.240-7T→G)). Among the controls, a single individual was found to be heterozygous for a silent mutation A140A.