Rare genetic variants involved in multisystem inflammatory syndrome in children: a multicenter Brazilian cohort study
IntroductionDespite the existing data on the Multisystem Inflammatory Syndrome in Children (MIS-C), the factors that determine these patients evolution remain elusive. Answers may lie, at least in part, in genetics. It is currently under investigation that MIS-C patients may have an underlying innat...
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1182257/full |
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| author | Bárbara Carvalho Santos Dos Reis Bárbara Carvalho Santos Dos Reis Bárbara Carvalho Santos Dos Reis Roberta Soares Faccion Roberta Soares Faccion Flavia Amendola Anisio de Carvalho Flavia Amendola Anisio de Carvalho Daniella Campelo Batalha Cox Moore Daniella Campelo Batalha Cox Moore Maria Celia Chaves Zuma Maria Celia Chaves Zuma Desirée Rodrigues Plaça Desirée Rodrigues Plaça Igor Salerno Filgueiras Dennyson Leandro Mathias Fonseca Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Adriana Cesar Bonomo Adriana Cesar Bonomo Adriana Cesar Bonomo Adriana Cesar Bonomo Wilson Savino Wilson Savino Wilson Savino Wilson Savino Flávia Cristina de Paula Freitas Helisson Faoro Fabio Passetti Jaqueline Rodrigues Robaina Felipe Rezende Caino de Oliveira Ana Paula Novaes Bellinat Raquel de Seixas Zeitel Margarida dos Santos Salú Margarida dos Santos Salú Margarida dos Santos Salú Mariana Barros Genuíno de Oliveira Gustavo Rodrigues-Santos Arnaldo Prata-Barbosa Arnaldo Prata-Barbosa Zilton Farias Meira de Vasconcelos |
| author_facet | Bárbara Carvalho Santos Dos Reis Bárbara Carvalho Santos Dos Reis Bárbara Carvalho Santos Dos Reis Roberta Soares Faccion Roberta Soares Faccion Flavia Amendola Anisio de Carvalho Flavia Amendola Anisio de Carvalho Daniella Campelo Batalha Cox Moore Daniella Campelo Batalha Cox Moore Maria Celia Chaves Zuma Maria Celia Chaves Zuma Desirée Rodrigues Plaça Desirée Rodrigues Plaça Igor Salerno Filgueiras Dennyson Leandro Mathias Fonseca Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Adriana Cesar Bonomo Adriana Cesar Bonomo Adriana Cesar Bonomo Adriana Cesar Bonomo Wilson Savino Wilson Savino Wilson Savino Wilson Savino Flávia Cristina de Paula Freitas Helisson Faoro Fabio Passetti Jaqueline Rodrigues Robaina Felipe Rezende Caino de Oliveira Ana Paula Novaes Bellinat Raquel de Seixas Zeitel Margarida dos Santos Salú Margarida dos Santos Salú Margarida dos Santos Salú Mariana Barros Genuíno de Oliveira Gustavo Rodrigues-Santos Arnaldo Prata-Barbosa Arnaldo Prata-Barbosa Zilton Farias Meira de Vasconcelos |
| author_sort | Bárbara Carvalho Santos Dos Reis |
| collection | DOAJ |
| description | IntroductionDespite the existing data on the Multisystem Inflammatory Syndrome in Children (MIS-C), the factors that determine these patients evolution remain elusive. Answers may lie, at least in part, in genetics. It is currently under investigation that MIS-C patients may have an underlying innate error of immunity (IEI), whether of monogenic, digenic, or even oligogenic origin.MethodsTo further investigate this hypothesis, 30 patients with MIS-C were submitted to whole exome sequencing. ResultsAnalyses of genes associated with MIS-C, MIS-A, severe covid-19, and Kawasaki disease identified twenty-nine patients with rare potentially damaging variants (50 variants were identified in 38 different genes), including those previously described in IFNA21 and IFIH1 genes, new variants in genes previously described in MIS-C patients (KMT2D, CFB, and PRF1), and variants in genes newly associated to MIS-C such as APOL1, TNFRSF13B, and G6PD. In addition, gene ontology enrichment pointed to the involvement of thirteen major pathways, including complement system, hematopoiesis, immune system development, and type II interferon signaling, that were not yet reported in MIS-C.DiscussionThese data strongly indicate that different gene families may favor MIS- C development. Larger cohort studies with healthy controls and other omics approaches, such as proteomics and RNAseq, will be precious to better understanding the disease dynamics. |
| first_indexed | 2024-03-12T20:52:52Z |
| format | Article |
| id | doaj.art-1ef99c613f3946aa902feb83e4209084 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-03-12T20:52:52Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-1ef99c613f3946aa902feb83e42090842023-07-31T23:04:00ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882023-07-011310.3389/fcimb.2023.11822571182257Rare genetic variants involved in multisystem inflammatory syndrome in children: a multicenter Brazilian cohort studyBárbara Carvalho Santos Dos Reis0Bárbara Carvalho Santos Dos Reis1Bárbara Carvalho Santos Dos Reis2Roberta Soares Faccion3Roberta Soares Faccion4Flavia Amendola Anisio de Carvalho5Flavia Amendola Anisio de Carvalho6Daniella Campelo Batalha Cox Moore7Daniella Campelo Batalha Cox Moore8Maria Celia Chaves Zuma9Maria Celia Chaves Zuma10Desirée Rodrigues Plaça11Desirée Rodrigues Plaça12Igor Salerno Filgueiras13Dennyson Leandro Mathias Fonseca14Otavio Cabral-Marques15Otavio Cabral-Marques16Otavio Cabral-Marques17Otavio Cabral-Marques18Otavio Cabral-Marques19Otavio Cabral-Marques20Adriana Cesar Bonomo21Adriana Cesar Bonomo22Adriana Cesar Bonomo23Adriana Cesar Bonomo24Wilson Savino25Wilson Savino26Wilson Savino27Wilson Savino28Flávia Cristina de Paula Freitas29Helisson Faoro30Fabio Passetti31Jaqueline Rodrigues Robaina32Felipe Rezende Caino de Oliveira33Ana Paula Novaes Bellinat34Raquel de Seixas Zeitel35Margarida dos Santos Salú36Margarida dos Santos Salú37Margarida dos Santos Salú38Mariana Barros Genuíno de Oliveira39Gustavo Rodrigues-Santos40Arnaldo Prata-Barbosa41Arnaldo Prata-Barbosa42Zilton Farias Meira de Vasconcelos43Programa de Pós Graduação em Pesquisa Aplicada à Saúde da Criança e da Mulher, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ, BrazilLaboratório de Alta Complexidade (LACIFF), Unidade de Pesquisa Clínica, IFF, FIOCRUZ, Rio de Janeiro, RJ, BrazilDepartamento de Imunologia, IFF, FIOCRUZ, Rio de Janeiro, RJ, BrazilPrograma de Pós Graduação em Pesquisa Aplicada à Saúde da Criança e da Mulher, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ, BrazilLaboratório de Alta Complexidade (LACIFF), Unidade de Pesquisa Clínica, IFF, FIOCRUZ, Rio de Janeiro, RJ, BrazilPrograma de Pós Graduação em Pesquisa Aplicada à Saúde da Criança e da Mulher, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ, BrazilDepartamento de Imunologia, IFF, FIOCRUZ, Rio de Janeiro, RJ, BrazilUnidade de Pacientes Graves, Departamento de Pediatria, IFF, FIOCRUZ, Rio de Janeiro, RJ, BrazilFaculdade de Medicina, Universidade Federal Fluminense, Niterói, Rio de Janeiro, RJ, BrazilPrograma de Pós Graduação em Pesquisa Aplicada à Saúde da Criança e da Mulher, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ, BrazilLaboratório de Alta Complexidade (LACIFF), Unidade de Pesquisa Clínica, IFF, FIOCRUZ, Rio de Janeiro, RJ, BrazilDepartamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas (FCF), Universidade de São Paulo (USP), São Paulo, SP, BrazilPrograma de Pós-Graduação em Farmácia (Fisiopatologia e Toxicologia), FCF, USP, São Paulo, SP, BrazilDepartamento de Imunologia, Instituto de Ciências Biomédicas (ICB), USP, São Paulo, SP, BrazilPrograma Interunidades de Pós-graduação em Bioinformática, Instituto de Matemática e Estatística (IME), USP, São Paulo, SP, BrazilDepartamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas (FCF), Universidade de São Paulo (USP), São Paulo, SP, BrazilDepartamento de Imunologia, Instituto de Ciências Biomédicas (ICB), USP, São Paulo, SP, BrazilPrograma Interunidades de Pós-graduação em Bioinformática, Instituto de Matemática e Estatística (IME), USP, São Paulo, SP, Brazil0Network of Immunity in Infection, Malignancy, and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), São Paulo, Brazil1Department of Medicine, Division of Molecular Medicine, University of São Paulo School of Medicine, São Paulo, SP, Brazil2Laboratory of Medical Investigation 29, University of São Paulo School of Medicine, São Paulo, Brazil3Laboratoírio de Pesquisas Sobre o Timo, Instituto Oswaldo Cruz (IOC), FIOCRUZ, Rio de Janeiro, RJ, Brazil4Instituto National de Ciencia e Tecnologia em Neuroimunomodulação (INCT/NIM), IOC, FIOCRUZ, Rio de Janeiro, RJ, Brazil5Rede FAPERJ de Pesquisa em Neuroinflamação, IOC, FIOCRUZ, Rio de Janeiro, RJ, Brazil6Rede INOVA-IOC em Neuroimunomodulação, IOC, FIOCRUZ, Rio de Janeiro, RJ, Brazil3Laboratoírio de Pesquisas Sobre o Timo, Instituto Oswaldo Cruz (IOC), FIOCRUZ, Rio de Janeiro, RJ, Brazil4Instituto National de Ciencia e Tecnologia em Neuroimunomodulação (INCT/NIM), IOC, FIOCRUZ, Rio de Janeiro, RJ, Brazil5Rede FAPERJ de Pesquisa em Neuroinflamação, IOC, FIOCRUZ, Rio de Janeiro, RJ, Brazil6Rede INOVA-IOC em Neuroimunomodulação, IOC, FIOCRUZ, Rio de Janeiro, RJ, Brazil7Laboratório de Regulação da Expressão Gênica, Instituto Carlos Chagas (ICC), FIOCRUZ, Curitiba, PR, Brazil7Laboratório de Regulação da Expressão Gênica, Instituto Carlos Chagas (ICC), FIOCRUZ, Curitiba, PR, Brazil7Laboratório de Regulação da Expressão Gênica, Instituto Carlos Chagas (ICC), FIOCRUZ, Curitiba, PR, Brazil8Instituto D’Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, Brazil9Pediatric Intensive Care Unit, Hospital Alvorada Moema, São Paulo, SP, Brazil0Pediatric Intensive Care Unit, Hospital Martagão Gesteira, Salvador, BA, Brazil1Pediatric Intensive Care Unit, Hospital Universitário Pedro Ernesto (HUPE), Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, BrazilPrograma de Pós Graduação em Pesquisa Aplicada à Saúde da Criança e da Mulher, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ, BrazilLaboratório de Alta Complexidade (LACIFF), Unidade de Pesquisa Clínica, IFF, FIOCRUZ, Rio de Janeiro, RJ, Brazil0Pediatric Intensive Care Unit, Hospital Martagão Gesteira, Salvador, BA, Brazil8Instituto D’Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, Brazil8Instituto D’Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, Brazil8Instituto D’Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, Brazil2Pediatric Intensive Care Unit, Instituto de Puericultura e Pediatria Martagão Gesteira (IPPMG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilLaboratório de Alta Complexidade (LACIFF), Unidade de Pesquisa Clínica, IFF, FIOCRUZ, Rio de Janeiro, RJ, BrazilIntroductionDespite the existing data on the Multisystem Inflammatory Syndrome in Children (MIS-C), the factors that determine these patients evolution remain elusive. Answers may lie, at least in part, in genetics. It is currently under investigation that MIS-C patients may have an underlying innate error of immunity (IEI), whether of monogenic, digenic, or even oligogenic origin.MethodsTo further investigate this hypothesis, 30 patients with MIS-C were submitted to whole exome sequencing. ResultsAnalyses of genes associated with MIS-C, MIS-A, severe covid-19, and Kawasaki disease identified twenty-nine patients with rare potentially damaging variants (50 variants were identified in 38 different genes), including those previously described in IFNA21 and IFIH1 genes, new variants in genes previously described in MIS-C patients (KMT2D, CFB, and PRF1), and variants in genes newly associated to MIS-C such as APOL1, TNFRSF13B, and G6PD. In addition, gene ontology enrichment pointed to the involvement of thirteen major pathways, including complement system, hematopoiesis, immune system development, and type II interferon signaling, that were not yet reported in MIS-C.DiscussionThese data strongly indicate that different gene families may favor MIS- C development. Larger cohort studies with healthy controls and other omics approaches, such as proteomics and RNAseq, will be precious to better understanding the disease dynamics. https://www.frontiersin.org/articles/10.3389/fcimb.2023.1182257/fullmultisystem inflammatory syndrome in childrenpediatric inflammatory multisystem syndromecoronavirus infectionmucocutaneous lymph node syndromeKawasaki diseasewhole exome sequencing |
| spellingShingle | Bárbara Carvalho Santos Dos Reis Bárbara Carvalho Santos Dos Reis Bárbara Carvalho Santos Dos Reis Roberta Soares Faccion Roberta Soares Faccion Flavia Amendola Anisio de Carvalho Flavia Amendola Anisio de Carvalho Daniella Campelo Batalha Cox Moore Daniella Campelo Batalha Cox Moore Maria Celia Chaves Zuma Maria Celia Chaves Zuma Desirée Rodrigues Plaça Desirée Rodrigues Plaça Igor Salerno Filgueiras Dennyson Leandro Mathias Fonseca Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Otavio Cabral-Marques Adriana Cesar Bonomo Adriana Cesar Bonomo Adriana Cesar Bonomo Adriana Cesar Bonomo Wilson Savino Wilson Savino Wilson Savino Wilson Savino Flávia Cristina de Paula Freitas Helisson Faoro Fabio Passetti Jaqueline Rodrigues Robaina Felipe Rezende Caino de Oliveira Ana Paula Novaes Bellinat Raquel de Seixas Zeitel Margarida dos Santos Salú Margarida dos Santos Salú Margarida dos Santos Salú Mariana Barros Genuíno de Oliveira Gustavo Rodrigues-Santos Arnaldo Prata-Barbosa Arnaldo Prata-Barbosa Zilton Farias Meira de Vasconcelos Rare genetic variants involved in multisystem inflammatory syndrome in children: a multicenter Brazilian cohort study Frontiers in Cellular and Infection Microbiology multisystem inflammatory syndrome in children pediatric inflammatory multisystem syndrome coronavirus infection mucocutaneous lymph node syndrome Kawasaki disease whole exome sequencing |
| title | Rare genetic variants involved in multisystem inflammatory syndrome in children: a multicenter Brazilian cohort study |
| title_full | Rare genetic variants involved in multisystem inflammatory syndrome in children: a multicenter Brazilian cohort study |
| title_fullStr | Rare genetic variants involved in multisystem inflammatory syndrome in children: a multicenter Brazilian cohort study |
| title_full_unstemmed | Rare genetic variants involved in multisystem inflammatory syndrome in children: a multicenter Brazilian cohort study |
| title_short | Rare genetic variants involved in multisystem inflammatory syndrome in children: a multicenter Brazilian cohort study |
| title_sort | rare genetic variants involved in multisystem inflammatory syndrome in children a multicenter brazilian cohort study |
| topic | multisystem inflammatory syndrome in children pediatric inflammatory multisystem syndrome coronavirus infection mucocutaneous lymph node syndrome Kawasaki disease whole exome sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1182257/full |
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