Clinical and genetic findings in two siblings with X-Linked agammaglobulinemia and bronchiolitis obliterans: a case report

Detalhes bibliográficos
Autor(a) principal: Francisco Junior, Ronaldo da Silva
Data de Publicação: 2022
Outros Autores: Morais, Guilherme Loss de, Carvalho, Joseane Biso de, Ferreira, Cristina dos Santos, Gerber, Alexandra Lehmkuhl, Guimarães, Ana Paula de C., Amendola, Flávia Anisio, Pinto-Mariz, Fernanda, Vasconcelos, Zilton Farias Meira de, Goudouris, Ekaterini Simões, Vasconcelos, Ana Tereza Ribeiro de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/54639
Resumo: Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro – FAPERJ #E-26/202.826/2018 (BR) and #E-26/210.086/2022 (BR)
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spelling Francisco Junior, Ronaldo da SilvaMorais, Guilherme Loss deCarvalho, Joseane Biso deFerreira, Cristina dos SantosGerber, Alexandra LehmkuhlGuimarães, Ana Paula de C.Amendola, Flávia AnisioPinto-Mariz, FernandaVasconcelos, Zilton Farias Meira deGoudouris, Ekaterini SimõesVasconcelos, Ana Tereza Ribeiro de2022-08-15T13:37:26Z2022-08-15T13:37:26Z2022FRANCISCO JUNIOR, Ronaldo da Silva et al. Clinical and genetic findings in two siblings with X-Linked agammaglobulinemia and bronchiolitis obliterans: a case report. BMC Pediatrics, v. 22, n. 181, p. 1-5, 5 Apr. 2022.1471-2431https://www.arca.fiocruz.br/handle/icict/5463910.1186/s12887-022-03245-x1471-2431Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro – FAPERJ #E-26/202.826/2018 (BR) and #E-26/210.086/2022 (BR)Conselho Nacional de Desenvolvimento Científco e Tecnológico–CNPq # 303170/2017–4 (BR)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) [Grant: Biocomputacional #23038.010041/2013¬13]RSFJ received graduate fellowships from the Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–CAPESLaboratório Nacional de Computação Científica. Petrópolis, RJ, Brasil.Laboratório Nacional de Computação Científica. Petrópolis, RJ, Brasil.Laboratório Nacional de Computação Científica. Petrópolis, RJ, Brasil.Laboratório Nacional de Computação Científica. Petrópolis, RJ, Brasil.Laboratório Nacional de Computação Científica. Petrópolis, RJ, Brasil.Laboratório Nacional de Computação Científica. Petrópolis, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Laboratório de Alta Complexidade. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Puericultura e Pediatria Martagão Gesteira. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Laboratório de Alta Complexidade. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Puericultura e Pediatria Martagão Gesteira. Rio de Janeiro, RJ, Brasil.Laboratório Nacional de Computação Científica. Petrópolis, RJ, Brasil.Background: X-linked agammaglobulinemia (XLA) is an Inborn Errors of Immunity (IEI) characterized by pan-hypogammaglobulinemia and low numbers of B lymphocytes due to mutations in BTK gene. Usually, XLA patients are not susceptible to respiratory tract infections by viruses and do not present interstitial lung disease (ILD) such as bronchiolitis obliterans (BO) as a consequence of acute or chronic bacterial infections of the respiratory tract. Although many pathogenic variants have already been described in XLA, the heterogeneous clinical presentations in affected patients suggest a more complex genetic landscape underlying this disorder. Case presentation: We report two pediatric cases from male siblings with X-Linked Agammaglobulinemia and bronchiolitis obliterans, a phenotype not often observed in XLA phenotype. The whole-exome sequencing (WES) analysis showed a rare hemizygous missense variant NM_000061.2(BTK):c.1751G>A(p.Gly584Glu) in BTK gene of both patients. We also identified a gain-of-function mutation in TGFβ1 (rs1800471) previously associated with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation. TGFβ1 plays a key role in the regulation of immune processes and inflammatory response associated with pulmonary impairment. Conclusions: Our report illustrates a possible role for WES in patients with known inborn errors of immunity, but uncommon clinical presentations, providing a personalized understanding of genetic basis, with possible implications in the identification of potential treatments, and prognosis for patients and their families.engBMCClinical and genetic findings in two siblings with X-Linked agammaglobulinemia and bronchiolitis obliterans: a case reportinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleX-linked agammaglobulinemiaBTKWhole-exome sequencingBronchiolitis obliteransinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83132https://www.arca.fiocruz.br/bitstream/icict/54639/1/license.txt33967fcc8ef681b8f5c2c34178ebc114MD51ORIGINALClinical and genetic findings in two siblings with X-Linked agammaglobulinemia and bronchiolitis obliterans - a case report.pdfClinical and genetic findings in two siblings with X-Linked agammaglobulinemia and bronchiolitis obliterans - a case report.pdfapplication/pdf1051366https://www.arca.fiocruz.br/bitstream/icict/54639/2/Clinical%20and%20genetic%20findings%20in%20two%20siblings%20with%20X-Linked%20agammaglobulinemia%20and%20bronchiolitis%20obliterans%20-%20a%20case%20report.pdf2fecac43ffd14ecb6ec7972401704446MD52icict/546392022-08-15 10:40:34.456oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352022-08-15T13:40:34Repositório Institucional da FIOCRUZ (ARCA) - 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dc.title.pt_BR.fl_str_mv Clinical and genetic findings in two siblings with X-Linked agammaglobulinemia and bronchiolitis obliterans: a case report
title Clinical and genetic findings in two siblings with X-Linked agammaglobulinemia and bronchiolitis obliterans: a case report
spellingShingle Clinical and genetic findings in two siblings with X-Linked agammaglobulinemia and bronchiolitis obliterans: a case report
Francisco Junior, Ronaldo da Silva
X-linked agammaglobulinemia
BTK
Whole-exome sequencing
Bronchiolitis obliterans
title_short Clinical and genetic findings in two siblings with X-Linked agammaglobulinemia and bronchiolitis obliterans: a case report
title_full Clinical and genetic findings in two siblings with X-Linked agammaglobulinemia and bronchiolitis obliterans: a case report
title_fullStr Clinical and genetic findings in two siblings with X-Linked agammaglobulinemia and bronchiolitis obliterans: a case report
title_full_unstemmed Clinical and genetic findings in two siblings with X-Linked agammaglobulinemia and bronchiolitis obliterans: a case report
title_sort Clinical and genetic findings in two siblings with X-Linked agammaglobulinemia and bronchiolitis obliterans: a case report
author Francisco Junior, Ronaldo da Silva
author_facet Francisco Junior, Ronaldo da Silva
Morais, Guilherme Loss de
Carvalho, Joseane Biso de
Ferreira, Cristina dos Santos
Gerber, Alexandra Lehmkuhl
Guimarães, Ana Paula de C.
Amendola, Flávia Anisio
Pinto-Mariz, Fernanda
Vasconcelos, Zilton Farias Meira de
Goudouris, Ekaterini Simões
Vasconcelos, Ana Tereza Ribeiro de
author_role author
author2 Morais, Guilherme Loss de
Carvalho, Joseane Biso de
Ferreira, Cristina dos Santos
Gerber, Alexandra Lehmkuhl
Guimarães, Ana Paula de C.
Amendola, Flávia Anisio
Pinto-Mariz, Fernanda
Vasconcelos, Zilton Farias Meira de
Goudouris, Ekaterini Simões
Vasconcelos, Ana Tereza Ribeiro de
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Francisco Junior, Ronaldo da Silva
Morais, Guilherme Loss de
Carvalho, Joseane Biso de
Ferreira, Cristina dos Santos
Gerber, Alexandra Lehmkuhl
Guimarães, Ana Paula de C.
Amendola, Flávia Anisio
Pinto-Mariz, Fernanda
Vasconcelos, Zilton Farias Meira de
Goudouris, Ekaterini Simões
Vasconcelos, Ana Tereza Ribeiro de
dc.subject.en.pt_BR.fl_str_mv X-linked agammaglobulinemia
BTK
Whole-exome sequencing
Bronchiolitis obliterans
topic X-linked agammaglobulinemia
BTK
Whole-exome sequencing
Bronchiolitis obliterans
description Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro – FAPERJ #E-26/202.826/2018 (BR) and #E-26/210.086/2022 (BR)
publishDate 2022
dc.date.accessioned.fl_str_mv 2022-08-15T13:37:26Z
dc.date.available.fl_str_mv 2022-08-15T13:37:26Z
dc.date.issued.fl_str_mv 2022
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv FRANCISCO JUNIOR, Ronaldo da Silva et al. Clinical and genetic findings in two siblings with X-Linked agammaglobulinemia and bronchiolitis obliterans: a case report. BMC Pediatrics, v. 22, n. 181, p. 1-5, 5 Apr. 2022.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/54639
dc.identifier.issn.pt_BR.fl_str_mv 1471-2431
dc.identifier.doi.none.fl_str_mv 10.1186/s12887-022-03245-x
dc.identifier.eissn.none.fl_str_mv 1471-2431
identifier_str_mv FRANCISCO JUNIOR, Ronaldo da Silva et al. Clinical and genetic findings in two siblings with X-Linked agammaglobulinemia and bronchiolitis obliterans: a case report. BMC Pediatrics, v. 22, n. 181, p. 1-5, 5 Apr. 2022.
1471-2431
10.1186/s12887-022-03245-x
url https://www.arca.fiocruz.br/handle/icict/54639
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BMC
publisher.none.fl_str_mv BMC
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
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collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/54639/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/54639/2/Clinical%20and%20genetic%20findings%20in%20two%20siblings%20with%20X-Linked%20agammaglobulinemia%20and%20bronchiolitis%20obliterans%20-%20a%20case%20report.pdf
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
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