| Author | Francisco Junior, Ronaldo da Silva | |
| Author | Morais, Guilherme Loss de | |
| Author | Carvalho, Joseane Biso de | |
| Author | Ferreira, Cristina dos Santos | |
| Author | Gerber, Alexandra Lehmkuhl | |
| Author | Guimarães, Ana Paula de C. | |
| Author | Amendola, Flávia Anisio | |
| Author | Pinto-Mariz, Fernanda | |
| Author | Vasconcelos, Zilton Farias Meira de | |
| Author | Goudouris, Ekaterini Simões | |
| Author | Vasconcelos, Ana Tereza Ribeiro de | |
| Access date | 2022-08-15T13:37:26Z | |
| Available date | 2022-08-15T13:37:26Z | |
| Document date | 2022 | |
| Citation | 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. | pt_BR |
| ISSN | 1471-2431 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/54639 | |
| Sponsorship | 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) | pt_BR |
| Sponsorship | Conselho Nacional de Desenvolvimento Científco e Tecnológico–CNPq # 303170/2017–4 (BR) | pt_BR |
| Sponsorship | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) [Grant: Biocomputacional #23038.010041/2013¬13] | pt_BR |
| Sponsorship | RSFJ received graduate fellowships from the Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–CAPES | pt_BR |
| Language | eng | pt_BR |
| Publisher | BMC | pt_BR |
| Rights | open access | |
| Title | Clinical and genetic findings in two siblings with X-Linked agammaglobulinemia and bronchiolitis obliterans: a case report | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1186/s12887-022-03245-x | |
| Abstract | 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. | pt_BR |
| Affilliation | Laboratório Nacional de Computação Científica. Petrópolis, RJ, Brasil. | pt_BR |
| Affilliation | Laboratório Nacional de Computação Científica. Petrópolis, RJ, Brasil. | pt_BR |
| Affilliation | Laboratório Nacional de Computação Científica. Petrópolis, RJ, Brasil. | pt_BR |
| Affilliation | Laboratório Nacional de Computação Científica. Petrópolis, RJ, Brasil. | pt_BR |
| Affilliation | Laboratório Nacional de Computação Científica. Petrópolis, RJ, Brasil. | pt_BR |
| Affilliation | Laboratório Nacional de Computação Científica. Petrópolis, RJ, Brasil. | pt_BR |
| Affilliation | 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. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Puericultura e Pediatria Martagão Gesteira. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | 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. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Puericultura e Pediatria Martagão Gesteira. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Laboratório Nacional de Computação Científica. Petrópolis, RJ, Brasil. | pt_BR |
| Subject | X-linked agammaglobulinemia | pt_BR |
| Subject | BTK | pt_BR |
| Subject | Whole-exome sequencing | pt_BR |
| Subject | Bronchiolitis obliterans | pt_BR |
| e-ISSN | 1471-2431 | |
