Coexistence of dominant and recessive familial amyotrophic lateral sclerosis with the D90A Cu,Zn superoxide dismutase mutation within the same country

The Cu,Zn superoxide dismutase (Cu,Zn SOD) mutations described in amyotroph ic lateral sclerosis (ALS) have, for the most part, a dominant influence. H owever, while a few cases with a heterozygous D90A mutation have been descr ibed in different countries, D90A has been recently proven to be recessivel y inherited with a common founder effect in Scandinavia. We screened French ALS families for Cu,Zn SOD mutations. The presence of the D90A allele was found in two index-cases, and their families were subsequently studied. In the first family the ALS patients were homozygotes for D90A, while in the s econd, all ALS patients were heterozygotes. In both families the disease wa s found to initially involve the lower limbs with slower progression than i n sporadic cases, and frequent atypical signs such as paresthesia and urgen cy of micturition. We determined the D90A allele frequency in controls (n = 200) and sporadic ALS patients (n = 408). No D90A allele was found. This i s the first report of coexistence of dominant and recessive families with t he D90A Cu,Zn SOD mutation within the same country.