Rare Genetic Variants of NLRP12 in Admixed Latino-American Children With SARS-CoV-2–Related Multisystem Inflammatory Syndrome
Year: 2024
Type: article
Study design: Observational Study
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 nuclear factor-κB signaling. Nine rare, potentially deleterious variants were found in 8 of 21 patients, located in the IL17RC, IFNA10, or NLRP12 gene. Unlike the wild type NLRP12 protein, which inhibits nuclear factor-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.
Authors: Thaís M M Barreto, Roberta S Souza, Raquel B São Pedro, Isadora M Paiva, Andréia S Silva, Ana L Nogueira, Ana P N Bellinat, Nathália L S Dias, Sara Nunes, Gabriela S G Britto, Edson H B Amaral, Gabriela D Rocha, Carolina Silva-Carvalho, Ricardo Lyra, Fernanda S G Kehdy, Túlio L Campos, Patrícia M M F Moura, Eduardo Tarazona-Santos, Thiago M Cunha, Natália M Tavares, Marcus V B Oliveira-Sá, Regina C F Ramos, Rodrigo F Carmo, Luydson R S Vasconcelos, Pablo R S Oliveira
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
Award: G8044724622
OpenAlex ID: W4402900063