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
em 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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Papillomaviridae
/
Pseudomonas aeruginosa
/
Infecções por Pseudomonas
/
Viroses
/
Leucócitos Mononucleares
/
Meningites Bacterianas
/
Inibidor de NF-kappaB alfa
/
Mutação com Ganho de Função
/
Síndromes de Imunodeficiência
/
Neisseria meningitidis
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
Limite:
Adult
/
Child
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article