MISC (Çocuklarda Multisistemik İnflamatuar Sendrom) Tanılı Çocuk Olguların Klinik ve Genetik Risk Faktörlerinin Belirlenmesi

Project no. 23693 · Status: Kapanmış (Yayın bekleniyor) · 2023

Summary

Introduction: Multisystemic Inflammatory Syndrome, which develops approximately 14 days after infection in children with COVID-19, causes significant morbidity and mortality with severe cardiac and multisystemic involvement. Its development in only 0.01% to 0.001% of children after COVID-19 suggests that genetic factors influence the susceptibility to MIS-C disease. Therefore, the aim was to identify candidate genes that may cause genetic susceptibility in MIS-C patients.Method: Our study included 25 patients admitted to the Pediatric Infectious Diseases Department of Ege University Faculty of Medicine with a definitive diagnosis of MIS-C. Whole exome sequencing(WES) was performed on selected patients. To identify variants with autosomal recessive inheritance, which are at the forefront in patient selection, patients with consanguineous marriages in their family history and patients who subsequently met severe MIS-C criteria and were admitted to the Intensive Care Unit were included in the study. In the WES analysis results, genes classified as VUS, LP and P according to the ACMG criteria, especially genes in the pathways that may cause an increased inflammatory response and are previously involved in the pathogenesis of MIS-C, are presented.Results: In the WES analysis of 25 patients included in the study, new variants were identified fort he first time in 17 genes that may play a role in the etiopathogenesis of MIS-C. These variants are AIRE:c.927C>G, ELANE:c.223G>A, TNFRSF1A:c.1333G>A, CYP1B1:c.182G>A, TET2:c.3480T>G, TREX1:c.-26-1G. >A, KIF23:c.100C>A, TBX1:c.1456A>C, MVK:c.1129G>A, CYP1B1:c.1103G>A, CHEK2:c.1232G>A, CHRNE:c.-96C>T, RET:c.2257A>C, SOD1:c.272A>C, MYH7 :c.1750G>A, BCHE:c.435_436insG, RNASEH2B:c.830G>A. A large number of new variants have been identified in genes that are consistent with the clinical findings and have been reported in previous studies as potentially playing a role in the etiology. These variants are as followsNew variants in genes that are also clinically compatible and previously involved in etiology are POLG:c.1760C>T, POLG:c.752C>T, ABCA4:c.4253+43G>A, TNFRSF13B:c.198C>A, OAS1:c. 920A>T, ABCB6:c.985del, G6PD:c.1360C>T, CFTR:c.2756A>G, CFTR:c.3205G>A, ABCA4:c.5882G>A, ABCA4:c.3287C>T, C9:c.347G>A, ABCC6:c.1171A>G, TNFRSF13B: c.310T>C, ABCA4:c.2828G>A, MEFV:c.2177T>C, MPO:c.2031-2A>C, HLA-DRB1:c.303_304del, CFI:c.265_266del, CFI:c.1033C>T, TUBB1:c.757C>G, ABCA4: c.1139A>G, PRF1:c.1000G>A, CFTR:c.1624G>T was detected. It has been determined that the genes containing the identified variants play a role in mechanisms that could lead to hyperinflammation, particularly in the Type 1 interferonopathy pathway, complement activation, and the IL-1 beta pathway.New genes in the type 1 interferon pathway, new variants in proteins effective in complement activation, genes that may cause hyperinflammation in the IL-1 beta pathway, and at least VUS, LP and pathogenic variants in these genes according to the ACMG classification have been identified.Discussion and Results: In our study, new variants were identified in candidate genes that may be involved in the etiopathogenesis of MIS-C, as well as in genes previously reported to play a role in its etiopathogenesis. Our study will provide insights for future research investigating the functional disturbances that could arise from the defects identified in these genes.In our study, candidate genes that may be involved in the etiopathogenesis of MIS-C and new variants in the genes involved in this process were identified through previous studies. This study will shed light on studies evaluating changes in function or protein level that may occur with defects in these genes.

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