Our objective was to search for mutations in genes SOD1, TARDBP, C9orf72, ANG, ATXN2 and VEGF in Russian patients with amyotrophic lateral sclerosis (ALS). A group of 208 Russian patients with ALS was examined. Molecular genetic analysis was conducted using direct sequencing, fragment analysis, and real-time PCR. We found eight different point mutations in the SOD1 gene, with the frequency of mutations being 50% in familial ALS and 3% in sporadic ALS. No mutations were found in exon 6 of the TARDBP gene; however, deletion c.715-126delG in intron 5 of TARDBP was over-represented in ALS patients compared to controls (38% vs. 26.6%; χ(2 )= 13.17; p = 0.002). Hexanucleotide repeat expansion of the C9orf72 gene was revealed in 2.5% of sporadic ALS patients. Mutations in the ANG gene were identified in 1.5% of sporadic ALS patients. The presence of an intermediate number (28-33) of GAC repeats in the ATXN2 gene was observed significantly more often in the study group compared to the control group (5% vs. 1.7%; χ(2 )= 3.89; p = 0.0486). In the cohort examined, we found an association between the disease and the risk A-allele and the A/A genotype at the -2578С/А locus of the VEGF gene. In conclusion, we determined for the first time the genetic basis of ALS in a Russian population.

Cohorts of amyotrophic lateral sclerosis (ALS) patients and control individuals of Caucasian origin from the Central European Russia (Moscow city and region) were analyzed for the presence of hexanucleotide repeat GGGGCC expansion within the first intron of the C9ORF72 gene. The presence of a large (>40) repeat expansion was found in 15% of familial ALS cases (3 of 20 unrelated familial cases) and 2.5% of sporadic ALS cases (6 of 238) but in none of control cases. These results suggest that the frequency of C9ORF72 hexanucleotide repeats expansions in the Central European Russian ALS patients is significantly lower than in Western European or Northern American ALS patients of Caucasian origin but higher than in Asian ALS patients.

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Материалы и методы. Были обследованы 285 российских пациентов с боковым амиотрофическим склерозом (БАС), -represented -38.0 % vs. 26.6 % (χ 2 = 13.17; р = 0.002

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