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

of congenital heart defect. The girl has been ill since the age of 10 months, when a long-term fever, anemia (Hb 70-100 g/l), increased ESR (25-40 mm/h ) and CRP (24- 31 mg/l) occurred HLA-B27 (+) , A НФ - 1:1000. She received a course of antibacterial therapy, NSAIDs, which was ineffective. The character of disease was progressive, often recurrent with bouts of fever, arthralgias and edema of the knee, ankle, and wrist joints. Ultrasonography has revealed exudative and proliferative changes in the joints. The girl was diagnosed with juvenile idiopathic polyarthritis. Against the background of GCs therapy and methotrexate, a positive dynamics was obtained, but when the dose of GCs was reduced, the inflammatory process activated, which required the intensification of therapeutic measures. Genetic sequencing revealed a heterozygous change in the ADA2 gene c.145C>T (p.Arg49Trp), which encodes the adenosine deaminase 2 enzyme. This sequence change replaces arginine with tryptophan at the codon unit 49 of the ADA2 protein (p.Arg49Trp). The onset of systemic JIA in a girl was at the age of 8 years and was characterized by fever, skin rash, arthritis of the knee and hip joints, and myositis. Laboratory tests showed an increase in CRP (24-20 mg/l ), ESR( 68-20 mm/h), CPK (7086-145 U/l), LDH (707-645 U/l), ANA 1:1000, negative RF, HLA-B27 (+). In the treatment with systemic GCs, hydroxychlorhynine and methotrexate, positive dynamics were obtained, but with a decrease in GCs therapy, there is a constant disease recurrence, which required changes in the baseline therapy and initiation of biological immunotherapy. Genetic sequencing revealed a pathogenic mutation in the NLRP12 gene. Mutations in the NLRP12 gene determine the activation of NF-kB and caspase signaling pathways and are associated with autosomal dominant Familial cold autoinflammatory syndrome (FCAS) (MedGen UID 435869). The clinical significance of this variant remains uncertain. The sequence change replaces glycine with alanine at the 448 NLRP12 protein codon (p.Gly448Ala). This variant has been reported in a person suffering from chronic NLRP12 inflammation [Naderi N., 2011]. ClinVar contains an entry for this variant (variant ID: 97886). The available evidence is still insufficient to determine the role of this variant in the disease. Just as in case with FCAS, patients with NLRP12 experience periodic episodes of high temperature under the influence of cold, which last for 2-10 days every 3-4 weeks. Fever is usually followed by arthralgia, myalgia, abdominal pain, headache, lymphadenopathy, aphthae on the oral mucosa and skin rash. In a 3-year-old boy, the disease debuted at the age of 1.5 years, when a spotty rash appeared at the height of the temperature, arthralgia, arthritis of the right knee joint. Systemic JIA was established and GCs therapy, methotrexate were prescribed; it gave a short- term positive effect, but after the third administration there was an allergic reaction, so that the therapy was replaced with the administration of tocilizumab, which allowed to get a positive dynamics and cancel the GCs administration. After a year rash had gradually re- appeared in child; it spread all over the body; the GCs were prescribed again with a positive result. Genetic testing revealed a change in the nucleotide sequence in the PSTPIP1 gene (MedGen UID: 346801), which encodes a cytoskeletal protein. This protein is active in interaction with various inflammatory proteins; it binds to the cytoplasmic tail of CD2, the t-cell activation and adhesion effector, binds PEST type protein tyrosine phosphatases and directs them to c-Abl kinase to mediate c-Abl- dephosphorylation, thereby regulating the activity of c- Abl. It also interacts with pyrin, which is found in association with the cytoskeleton in myeloid/monocyte cells and modulates immunoregulatory functions. Mutations in this gene are associated with PAPA syndrome (Pyogenic Arthritis, Pyoderma gangrenosum and Acne) and disrupt the physiological signaling necessary for maintaining proper inflammatory response. The genetic defect leads to increased binding of pyrin to NLRP, which causes autoinflammatory reactions [Gupta V., 2018]. The clinical significance of the identified variant is uncertain. This sequence change replaces isoleucine with asparagine in the codon 269 of PSTPIP1 protein (p.Ile269Asn). The isoleucine residue is highly conserved and there is a large physical and chemical difference between isoleucine and asparagine. IV. D iscussion During genetic testing, 25.8 % of patients with JIA (with ILAR/ACR diagnostic criteria) were found to have mutations in the NOD2, NLRP3, ADA2, MEFV, and PSTPIP1 genes, which increases the risk of initiating auto inflammatory syndromes characterized by arthritis, recurrent episodes of inflammation, fever, etc. [Shnappauf O and Aksentijevich, 2019]. This paper did not aim to determine the distribution of all eles in genes at the population level, but only in a limited cohort of children with different JIA phenotypes. Therefore, follow-up studies in this regard are appropriate. It is difficult to correct the individual clinical phenotypes of JIA that we have presented with protocol treatment, which indicates the possibility of the existence of juvenile arthritis with genetic variants of auto inflammatory syndromes and disorders in certain functions of innate immunity: a burdened family anamnesis of autoimmune diseases in first degree relatives, acute onset of arthritis after bacterial or viral infections, prolonged fever, rash. It should be noted that these children did not have RF and ACCP, and most of them were HLA-B27 negative. 1 Year 2022 89 © 2022 Global Journals Global Journal of Science Frontier Research Volume XXII Issue ersion I VII ( G ) Autoinflammation Candidate Genes in Juvenile Idiopathic Arthritis