A novel NFKBIA variant substituting serine 36 of IκBα causes immunodeficiency with warts, bronchiectasis and juvenile rheumatoid arthritis in the absence of ectodermal dysplasia.
Clin Immunol
; 210: 108269, 2020 01.
Article
en En
| MEDLINE
| ID: mdl-31683054
ABSTRACT
Genetic studies have led to identification of an increasing number of monogenic primary immunodeficiency disorders. Monoallelic pathogenic gain-of-function (GOF) variants in NFKBIA, the gene encoding IκBα, result in an immunodeficiency disorder, typically accompanied by anhidrotic ectodermal dysplasia (EDA). So far, 14 patients with immunodeficiency due to NFKBIA GOF mutations have been reported. In this study we report three patients from the same family with immunodeficiency, presenting with recurrent respiratory tract infections, bronchiectasis and viral skin conditions due to a novel pathogenic NFKBIA variant (c.106â¯Tâ¯>â¯G, p.Ser36Ala), which results in reduced IκBα degradation. Immunological investigations revealed inadequate antibody responses against vaccine antigens, despite hypergammaglobulinemia. Interestingly, none of the studied patients displayed features of EDA. Therefore, missense NFKBIA variants substituting serine 36 of IκBα, differ from the rest of pathogenic GOF NFKBIA variants in that they cause combined immunodeficiency, even in the absence of EDA.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Papillomaviridae
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Pseudomonas aeruginosa
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Infecciones por Pseudomonas
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Virosis
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Leucocitos Mononucleares
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Meningitis Bacterianas
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Inhibidor NF-kappaB alfa
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Mutación con Ganancia de Función
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Síndromes de Inmunodeficiencia
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Neisseria meningitidis
Tipo de estudio:
Diagnostic_studies
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Etiology_studies
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Prognostic_studies
Límite:
Adult
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Child
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Humans
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Male
Idioma:
En
Revista:
Clin Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2020
Tipo del documento:
Article