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.

Genetics of familial amyotrophic lateral sclerosis

“…2021; 20 (3): 193-202 ций SOD1 наследуются АД [26], однако также описаны случаи с АР типом наследования [27,28]. Частота мутаций SOD1 варьирует от 12 до 23,5% пациентов с сБАС и 5-10% спорадических случаев заболевания [29,30]. В настоящее время описано более 100 мутаций гена SOD1, большинство из которых являются точечными.…”

The modifiers of amyotrophic lateral sclerosis survival and clinical trial design

“…Some genes are not only risk factors, but they may also be survival modifiers. Several studies have shown that UNC13A [3,57,58,] and ATXN2 [59,60,61] are associated with shorter survival in ALS. The type of mutation lying in the TARDBP super rich glycine-residue domain was associated with the worst survival [62 ].…”

Consumption of unregulated food items (false morels) and risk for neurodegenerative disease (amyotrophic lateral sclerosis)

“…Colorectal cancer is the second cause of cancer death (after breast cancer) in women and the third for men (after lung and stomach cancers), and both the incidence and mortality have increased since 2000 [28]. With respect to neurodegenerative disease, Russian research has focused mainly on genetic risk factors for ALS [29,30]. While Bunina bodies, the neuronal inclusions named for Russian neuropathologist Tat'yana Bunina [31], are seen in familial, sporadic and Guam cases of ALS [32], the epidemiology of ALS in the Russian Federation is not well developed [1].…”