Global Journal of Science Frontier Research, G: Bio-Tech & Genetics, Volume 22 Issue 2

PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ( Table 2 ) All examined patients had a burdened family history (missed miscarriages, autoimmune diseases in first degree relatives), frequent bacterial ( Campylobacter, Citrobacter, Escherichia, Helicobacter, Pseudomonas, Staphylococcus, Yersinia ) and/or viral infections during their lifetime. 80.0% of children had an early onset of joint syndrome (in the first 3-4 years of life) with varying degrees of activity and/or frequent relapses. Tothisday, JIA isconsidered a polygenicautoimmune disease with a heterogeneous clinical pattern, without defined clear bio markers of the disease and in sufficient response to existing therapies (nonsteroidalanti- inflammatory drugs, gluco corticosteroids, biologictreatment), associated within ability to obtains table clinical laboratory remission. Searching for new genetic changes not only ingenes associated with adaptive immunity, but also in innateimmunegenes, which are characterized by changes in the functions of the corresponding protein sencoded by the corresponding auto inflammatory genes (NOD2, NLRP12, MEFV, ADA2 and PSTPIP1) is of great interest. This paper presents studied mutations in 32 genes of auto inflammation in children with different phenotypes of JIA (n = 62), which were obtained from 62 children under thestudy. Mutations in auto-inflammatory genes have been detected in 9 (56.2 %) children who were negative for ANF (-) and in 7 (43.7%) ANF (+) positive children. There were more HLA-B27(-) negative patients in this group than positive ones: 10 ( 62.5 % ) and 6 (37.5%), respectively. Non-steroidal anti-inflammatory drugs (NSAIDs) therapy was ineffective for this children and positive results were obtained when the anti-inflammatory effect was increased due to gluco corticoids (GCs). All children received basic disease-modifying therapy, which did not allow them to get a stable clinical and laboratory remission, which was manifested in a slow progression of the pathological process. 4 patients (25,0%) with systemic JIA, 3 (18,75%) patients with polyarthritis and 9 (56,2%) patients with oligoarthritis had changes in the nucleotide sequence in auto inflammatory genes. The data obtained indicate that in oligoarthritis changes in the innate Immunity functioning are observed more often compared to the systemic form and polyarticular form of JIA. Mutations in auto inflammatory genes were detected in 6 (37.5 %) children negative for ANA and HLA-B27 and in 4 (25.0 %) children positive for ANA and HLA-B27 [OR=0,55; С I (0,12-2,53)]. Four children with systemic JIA and eight with oligoarthritis had heterozygous changes in NOD2: c.2104C> T (p.Arg702Trp). It is known that NOD2 gene mutations are classically relatable to an increased risk of Crohn's disease (PMID: 19713276), autosomal dominant Blau syndrome (MedGen UID: 348835). The most common NOD2 variants are: c.2104C> T (p.Arg702 Trp), c.2722G> C (p.Gly908Arg) and c.3019dupC (p.Leu1007Profs*2). But none of our patients at the time of the examination had clinical and laboratory data that indicated the presence of inflammatory bowel disease. NOD2 gene polymorphism exists in 1-3% of the population, which increases the risk of clinical manifestation 2-4 times in heterozygous and 7-9 times in homozygous conditions. 19.3% of patients with JIA have changes in the nucleotide sequence in the NOD2 gene, which determines a statistically significant difference with the population frequency [OR=11,76, CI (2,53-54,59), p<0,001]. This sequence change replaces arginine with tryptophan at cod on 702 of the NOD2 protein (p.Arg702Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs2066844, ExAC 3%), including multiple homozygous individuals. Numerous population-based case-control studies have shown that this variant confers an elevated risk of Crohn's disease [Peter I, Mitchell AA,2011; Hradsky O, 2008; Naderi N., 2011; Lakatos PL., 2005; Tukel T., 2004]. In a large meta-an alysis involving 75 case-control studies with 18,727 cases and 17,102 controls [Yazdanyar S., 2009 ], individuals carrying this variant had an increased overall risk of Crohn's disease (OR = 2.2, 95% CI 2.0-2.5). When all three NOD2 genotypes were combined (p.Arg702Trp, p.Gly908Arg, and p.Leu1007Profs*2), the odds ratios for Crohn's disease were 2.4 (95% CI, 2.0-2.8) for simple heterozygotes, 9.0 (95% CI 6.0-13.5) for compound heterozygotes, and 6.7 (95% CI 4.1-10.9) for homozygotes, compared with noncarriers. This variant is also referred to as R675W and SNP8 in the literature. ClinVar contains an entry for this variant (Variation ID: 4693). Experimental studies have shown that this missense change results in decreased NFkB activity and decreased response to lipopolysaccharide, muramyl dipeptide, and peptidoglycan compared to wild type protein [Bonen DK., 2003; Li J, Moran T., 2004; Stevens C, 2013] . In summary, this is a frequently observed variant that is associated with approximately a 2.2-fold increased risk of Crohn's disease in population studies. Therefore, it has been classified as an Increased Risk Allele. A 2-year-old girl of Arab origin is being observed in the children`s connective tissue disorder clinic. She was born in 5th pregnancy, complicated by toxicosis and the threatened miscarriage; the previous 2 pregnancies ended in miscarriages, 2 children were born, one of them died at the age of 1 month because © 2022 Global Journals 1 Year 2022 88 Global Journal of Science Frontier Research Volume XXII Issue ersion I VII ( G ) Autoinflammation Candidate Genes in Juvenile Idiopathic Arthritis