Multiple sclerosis (MS) is a neurodegenerative disease of unclear etiology with both environmental and genetic risk factors. Multiple genome wide association studies (GWAS) have been conducted, however it is necessary to identify more reliable disease markers based on rare genetic variants. For the purpose of better understanding its genetic risk factors exome sequencing was conducted beforehand - probands were divided into three groups: patients with familial MS, sporadic MS and the control group. The analysis included nucleotide variants of 938 genes previously associated with MS using GWAS. These genes were analyzed for rare gene variants based on the following criteria: minor allele frequency (MAF) < 0.05, CADD (combined annotation dependent depletion) score ⡥ 20 and absence from the control group with simultaneous presence in at least one group with MS. We determined 25 variants located in 19 genes that fit the criteria. Among them five genes contained more than one rare gene variant – SORBS2 contained three rare variants while AGAP2, CLEC16A, ELMO1 and RREB1 contained two variants each. Using the STRING and Enrichr tools we found that these 19 genes were enriched in biological pathways associated with MS, the immune system and autoimmune diseases. Five of the 19 genes were connected to the Wnt biological pathway: AHI1, AGAP2, KCNMA1, TCF7 and TNKS. With the discovery of rare pathological variants we have contributed to the understanding of MS' genetic components and with it to the development of potential future diagnostic methods. The role of candidate genes in the development of MS requires further research via functional analyses.
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