title: Genetic studies of Russian patients with amyotrophic lateral sclerosis.
abstract: 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.
authors.affiliation: a Research Centre of Neurology , Moscow , Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Lysogorskaia
authors.affiliation: a Research Centre of Neurology , Moscow , Russia.
authors.forename: Nataliya Yu
authors.initials: NY
authors.lastname: Abramycheva
authors.affiliation: a Research Centre of Neurology , Moscow , Russia.
authors.forename: Mariya N
authors.initials: MN
authors.lastname: Zakharova
authors.affiliation: a Research Centre of Neurology , Moscow , Russia.
authors.forename: Mariya S
authors.initials: MS
authors.lastname: Stepanova
authors.affiliation: a Research Centre of Neurology , Moscow , Russia.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Moroz
authors.affiliation: a Research Centre of Neurology , Moscow , Russia.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Rossokhin
authors.affiliation: a Research Centre of Neurology , Moscow , Russia.
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Illarioshkin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology* / Q000235:genetics*; D000067698:Ataxin-2 / Q000235:genetics*; D000073885:C9orf72 Protein; D004268:DNA-Binding Proteins / Q000235:genetics*; D019317:Evidence-Based Medicine; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D011506:Proteins / Q000235:genetics*; D015203:Reproducibility of Results; D018570:Risk Assessment; D012426:Russia / Q000453:epidemiology; D012680:Sensitivity and Specificity; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D055815:Young Adult
chemical_list: C000593752:ATXN2 protein, human; D000067698:Ataxin-2; D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D011506:Proteins; C000606290:SOD1 protein, human; C000598624:TARDBP protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: DNA; Genetics; RNA; SOD1; risk