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

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

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.

Afiliación

Francisco Junior RDS; Bioinformatics Laboratory-LABINFO, National Laboratory of Scientific Computation LNCC/MCTIC, Av. Getulio Vargas, 333, Quitandinha CEP: 25651-075 Petrópolis, Rio de Janeiro, Brazil.
de Morais GL; Bioinformatics Laboratory-LABINFO, National Laboratory of Scientific Computation LNCC/MCTIC, Av. Getulio Vargas, 333, Quitandinha CEP: 25651-075 Petrópolis, Rio de Janeiro, Brazil.
de Carvalho JB; Bioinformatics Laboratory-LABINFO, National Laboratory of Scientific Computation LNCC/MCTIC, Av. Getulio Vargas, 333, Quitandinha CEP: 25651-075 Petrópolis, Rio de Janeiro, Brazil.
Dos Santos Ferreira C; Bioinformatics Laboratory-LABINFO, National Laboratory of Scientific Computation LNCC/MCTIC, Av. Getulio Vargas, 333, Quitandinha CEP: 25651-075 Petrópolis, Rio de Janeiro, Brazil.
Gerber AL; Bioinformatics Laboratory-LABINFO, National Laboratory of Scientific Computation LNCC/MCTIC, Av. Getulio Vargas, 333, Quitandinha CEP: 25651-075 Petrópolis, Rio de Janeiro, Brazil.
de C Guimarães AP; Bioinformatics Laboratory-LABINFO, National Laboratory of Scientific Computation LNCC/MCTIC, Av. Getulio Vargas, 333, Quitandinha CEP: 25651-075 Petrópolis, Rio de Janeiro, Brazil.
Amendola FA; Laboratory of High Complexity of the Fernandes Figueira Institute (LACIFF) - Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
Pinto-Mariz F; Allergy and Immunology Service of the Martagão Gesteira Institute for Childcare and Pediatrics (IPPMG) - Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
de Vasconcelos ZFM; Laboratory of High Complexity of the Fernandes Figueira Institute (LACIFF) - Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil.
Goudouris ES; Allergy and Immunology Service of the Martagão Gesteira Institute for Childcare and Pediatrics (IPPMG) - Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
de Vasconcelos ATR; Bioinformatics Laboratory-LABINFO, National Laboratory of Scientific Computation LNCC/MCTIC, Av. Getulio Vargas, 333, Quitandinha CEP: 25651-075 Petrópolis, Rio de Janeiro, Brazil. atrv@lncc.br.

BMC Pediatr ; 22(1): 181, 2022 04 05.

Article en En | MEDLINE | ID: mdl-35382780

RESUMEN

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 TGFß1 (rs1800471) previously associated with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation. TGFß1 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.

Asunto(s)

Agammaglobulinemia; Bronquiolitis Obliterante; Enfermedades Genéticas Ligadas al Cromosoma X; Agammaglobulinemia Tirosina Quinasa/genética; Agammaglobulinemia/complicaciones; Agammaglobulinemia/diagnóstico; Agammaglobulinemia/genética; Niño; Análisis Mutacional de ADN; Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico; Enfermedades Genéticas Ligadas al Cromosoma X/genética; Humanos; Masculino; Mutación; Hermanos

Palabras clave

BTK; Bronchiolitis obliterans; Whole-exome sequencing; X-linked agammaglobulinemia

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bronquiolitis Obliterante / Agammaglobulinemia / Enfermedades Genéticas Ligadas al Cromosoma X Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Child / Humans / Male Idioma: En Revista: BMC Pediatr Asunto de la revista: PEDIATRIA Año: 2022 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido

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