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More than 140 different mutations have been reported in the Cu/Zn superoxide dismutase-1 ( SOD1) gene in patients with amyotrophic lateral sclerosis (ALS), some occurring as founder mutations. Occasionally, specific mutations are associated with a particular phenotype. We evaluated a possible genotype-phenotype correlation and looked for a founder effect in nine patients from six unrelated families with ALS, all carrying the G41S mutation, originating from north-west Tuscany in central Italy. Mutational analysis of the SOD1 gene was carried out by direct sequencing. A haplotype study was carried out using eight polymorphic markers flanking the SOD1 gene. The clinical pattern of the nine familial ALS (FALS) patients was characterized by spinal onset with early upper and lower motor neuron involvement, appearance of bulbar signs within one year, and death a few months later. Mean age at onset was 49.3 years and mean duration of disease was 0.9 years. Genotyping revealed a common haplotype for the G41S allele. We provide the first evidence that the G41S mutation in Italy originates from a common founder. In addition, our findings strengthen the data reported previously and indicate that the G41S mutation is consistently associated with a uniform and dramatic, fast-progressing phenotype. [ABSTRACT FROM AUTHOR]

Among the 140 Cu/Zn superoxide dismutase-1 (SOD1) gene mutations associated with ALS, only D90A, the most prevalent mutation in Europe, has been clearly shown to cause recessive and dominant ALS. Here we first describe two, apparently sporadic, Italian ALS patients heterozygous for the D90A mutation. One patient experienced early sensory involvement, confirmed by nerve biopsy. We review sensory symptoms in SOD1 ALS and discuss its possible origin in D90A heterozygous patients. [ABSTRACT FROM AUTHOR]