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
{"title":"Rare genetic variants of NLRP12 in Admixed Latino-American Children with SARS-CoV-2-related Multisystem Inflammatory Syndrome","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","doi":"10.1093/infdis/jiae480","DOIUrl":null,"url":null,"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.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Infectious Diseases","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/infdis/jiae480","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
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.