[Peculiarities of sporadic motor neuron disease associated with D90A and G12R mutations in Russian population]

Fifty-one blood samples of Russian patients with sporadic motor neuron disease were examined for mutations in Cu/Zn superoxide dismutase (SOD-1) gene. One female patient with amyotrophic lateral sclerosis (ALS) was heterozygous for G12R mutation. This patient suffered from ALS with cervical cord onset, pyramidal variant and fast progression. Mutation was also detected in her healthy son. Earlier, such mutation was described in 5 Italian patients with slow progressive ALS. Also, D90A SOD-1 gene associated haplotypes of the female ALS patients previously examined by the authors have been analyzed. A homozygous female patient with ALS was characterized by typical lumbar onset and extremely slow progression, as well as a female patient with heterozygous mutation and moderate progression carried so-called "Scandinavian" haplotype. To our knowledge, it is the first report on the finding of the haplotype considered as a "protective" one in the subjects heterozygous for D90A mutation with clinical symptoms of ALS. Mechanisms of "protective" influence of this haplotype on ALS course are not yet elucidated. Our finding suggests that the presence of "Scandinavian" haplotype does not completely protect from the disease development in patients exposed to other more pathogenic causative factors. This assumption is in line with modern conceptions on motor neuron disease as a complicated multifactor disorder.