Rare Genetic Variants of <i>NLRP12</i> in Admixed Latino-American Children With SARS-CoV-2–Related Multisystem Inflammatory Syndrome
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
- R.O.C. Lyra (ORCID: https://orcid.org/0000-0002-8334-7880)
- Thiago M. Cunha (ORCID: https://orcid.org/0000-0003-1084-0065)
- Rodrigo Feliciano do Carmo (ORCID: https://orcid.org/0000-0001-9601-6995)
- Fernanda S. G. Kehdy (ORCID: https://orcid.org/0000-0001-8964-9049)
- Pablo Rafael Silveira Oliveira (ORCID: https://orcid.org/0000-0001-9541-3737)
- Eduardo Tarazona‐Santos (ORCID: https://orcid.org/0000-0003-3508-3160)
- Carolina Silva-Carvalho (ORCID: https://orcid.org/0000-0002-6356-6779)
- Regina Coeli Ferreira Ramos
- Andreia Soares da Silva (ORCID: https://orcid.org/0000-0003-1600-6899)
- Isadora Marques Paiva (ORCID: https://orcid.org/0000-0002-2741-150X)
- Natália Machado Tavares (ORCID: https://orcid.org/0000-0002-4026-679X)
- Patrícia Moura (ORCID: https://orcid.org/0000-0003-4259-388X)
- Gabriela S G Britto
- Túlio de Lima Campos (ORCID: https://orcid.org/0000-0003-0446-848X)
- Luydson Richardson Silva Vasconcelos (ORCID: https://orcid.org/0000-0002-1625-3358)
- A NOGUEIRA
- Ana Paula Novaes Bellinat (ORCID: https://orcid.org/0000-0001-8562-0775)
- Sara Nunes (ORCID: https://orcid.org/0000-0001-8546-7598)
- Raquel B. São Pedro (ORCID: https://orcid.org/0000-0002-2443-321X)
- Marcus V B Oliveira-Sá
- Thaís M. M. Barreto
- Nathália L. S. Dias
- Edson H B Amaral (ORCID: https://orcid.org/0000-0001-5879-9212)
- Gabriela D Rocha
- Roberta S Souza
Institutions
- Universidade Federal de Minas Gerais (BR)
- Universidade Federal da Bahia (BR)
- Universidade de Ribeirão Preto (BR)
- Universidade de São Paulo (BR)
- Hospital del Salvador (CL)
- Instituto de Historia (ES)
- Hospital São Rafael (BR)
- Hospital Universitário Oswaldo Cruz (BR)
- Instituto de Tecnologia de Pernambuco (BR)
- Fundação Oswaldo Cruz (BR)
- Universidade Federal do Vale do São Francisco (BR)
- Universidade de Pernambuco (BR)
Publication Details
- Journal
- The Journal of Infectious Diseases
- Published
- 2024-09-27
- DOI
- https://doi.org/10.1093/infdis/jiae480
- Citations
- 3
- Primary Topic
- Kawasaki Disease and Coronary Complications
- Type
- article
- Field-Weighted Citation Impact
- 1.72