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In a group of 331 sporadic amyotrophic lateral sclerosis (ALS) cases, we identified a new Cu/Zn superoxide dismutase single base substitution, N19S, in two patients. In the first case, seven healthy family members of 15 carried the substitution. Controls (n = 268) and familial ALS index cases (n = 180) were screened and one control subject with N19S was identified. Our data show that, despite a possible role of susceptibility factor for ALS, N19S alone cannot be considered as a direct cause for the disease. Ann Neurol 2003;53:815–818

The telomeric copy (t) of the survival motor neuron (SMN) gene is homozygously deleted in more than 90% of patients with infantile motor neuron disease (MND). In the general population, no homozygous SMNt deletion has been found, whereas 5% of centromeric SMN (SMNc) deletions can be observed. Although SMNtdeletions appear causal for infantile and at least some adult‐onset spinal muscular atrophy (SMA) (type IV), the respective role of SMNdeletions remains unclear in adult‐onset MNDs. We studied SMN gene in three different groups of patients with adult‐onset MNDs. In sporadic amyotrophic lateral sclerosis (ALS; n = 177) ands familial ALS (n = 66), no SMNtdeletion had been found, and the frequency of SMNcdeletions was not increased. Converesly, among the 14 patients with sporadic pure lower MND (LMND), we found 2 patients with homozygous SMNtdeletions (14%) and 5 patients with homozygous SMNc deletions (36%). These data suggest that (1) SMNt deletions do not account for the major part, if any, of adult‐onset LMND cases; and (2) SMNcdeletions act as a susceptibility factor for LMNDs in adults. The clinical and gentic heterogeneity of LMND cases, including SMA type IV, are yet to be unexplained. Further studies on large groups of adult‐onset LMND patients are warranted to refine its nosology.