Author:
Francisco Junior Ronaldo da Silva,de Morais Guilherme Loss,de Carvalho Joseane Biso,dos Santos Ferreira Cristina,Gerber Alexandra Lehmkuhl,de C Guimarães Ana Paula,Amendola Flávia Anisio,Pinto-Mariz Fernanda,de Vasconcelos Zilton Farias Meira,Goudouris Ekaterini Simões,de Vasconcelos Ana Tereza Ribeiro
Abstract
AbstractBackgroundX-linked agammaglobulinemia (XLA) is an Inborn Errors of Immunity (IEI) characterized by pan-hypogammaglobulinemia and low numbers of B lymphocytes due to mutations inBTKgene. 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 presentationWe 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 BTKgene of both patients. We also identified a gain-of-function mutation inTGFβ1(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.ConclusionsOur 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.
Funder
Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Publisher
Springer Science and Business Media LLC
Subject
Pediatrics, Perinatology and Child Health
Cited by
3 articles.
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