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BIBTEX RIS

Rare genetic variants of NLRP12 in Admixed Latino-American Children with SARS-CoV-2-related Multisystem Inflammatory Syndrome

2024; Oxford University Press; Linguagem: Inglês

10.1093/infdis/jiae480

1537-6613

Thaís M. M. Barreto, Roberta S Souza, Raquel B. São Pedro, Isadora Marques Paiva, Andreia Soares da Silva, A NOGUEIRA, Ana Paula Novaes Bellinat, Nathália L. S. Dias, Sara Nunes, Gabriela S G Britto, Edson Henrique Bispo Amaral, Gabriela D Rocha, Carolina Silva-Carvalho, R.O.C. Lyra, Fernanda S. G. Kehdy, Túlio de Lima Campos, Patrícia Moura, Eduardo Tarazona‐Santos, Thiago M. Cunha, Natália Machado Tavares, Marcus V B Oliveira-Sá, Regina Coeli Ferreira Ramos, Rodrigo Feliciano do Carmo, Luydson Richardson Silva Vasconcelos, Pablo Rafael Silveira Oliveira,

COVID-19 Clinical Research Studies

Abstract Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare, potentially fatal complication of SARS-CoV-2 infection. Genetic defects in inflammation-related pathways have been linked to MIS-C, but additional research is needed, especially in diverse ethnic groups. The present study aimed to identify genetic variants underlying MIS-C in Brazilian patients. Whole-exome sequencing was performed, focusing on genes involved in the host immune response to SARS-CoV-2. Functional assays assessed the impact of selected variants on NF-κB signaling. Nine rare, potentially deleterious variants were found in eight of 21 patients, located in IL17RC, IFNA10, or NLRP12 genes. Unlike the wild-type NLRP12 protein, which inhibits NF-κB activation in HEK 293T cells, the mutant NLRP12 proteins have significantly reduced inhibitory properties. In conclusion, our results indicate that rare autosomal variants in immune-related genes may underlie MIS-C, highlighting the potential role of NLRP12 in its predisposition. These findings provide new insights for the appropriate management of MIS-C.