Therefore, rare heterozygous missense variants in DOCK8 and pHLH genes (PRF1, UNC13D, STXBP2, AP3B1, and LYST) in our MIS-C cohort may have contributed to the CSS pathology of these patients in a threshold model of disease, where a combination of severe infection and a baseline genetic partial defect in perforin-mediated cytolysis result in excess proinflammatory cytokine production [28]. This evidence concerns the gene STXBP2 and infection.