A novel CARD11 germline mutation in a Chinese patient of B cell expansion with NF-κB and T cell anergy (BENTA) and literature review
Germline gain-of-function (GOF) mutations in the CARD11 gene lead to a rare primary immunodeficiency disease known as B cell expansion with NF-κB and T cell anergy (BENTA). Affected patients present with a polyclonal expansion of B cells, lymphadenopathy, and splenomegaly. Herein, we report a novel...
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Published in | Frontiers in immunology Vol. 13; p. 943027 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
20.09.2022
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Subjects | |
Online Access | Get full text |
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Summary: | Germline gain-of-function (GOF) mutations in the
CARD11
gene lead to a rare primary immunodeficiency disease known as B cell expansion with NF-κB and T cell anergy (BENTA). Affected patients present with a polyclonal expansion of B cells, lymphadenopathy, and splenomegaly. Herein, we report a novel germline in-frame three base-pair deletion (c.1030_1032del, p.K344del) in the
CARD11
gene in a patient with atypical BENTA, presenting with a recurrent fever and B cell lymphocytosis. This mutation was inherited from his mother, who is clinically asymptomatic and had a recurrent respiratory tract infection in her childhood.
In vitro
functional analysis demonstrated that this variant decreased the expression level of the CARD11 protein and activated the NF-κB signal pathway, leading to a higher expression of several NF-κB target gene transcripts in HCT116 cells transfected with mutant CARD11 (K344del-CARD11) as revealed by RNA sequencing analysis. To our knowledge, only 23 BENTA patients have been identified and carried seven distinct GOF mutations in
CARD11
. The clinical manifestations of patients are highly heterogeneous and there was no significant correlation between genotype and phenotype. In summary, we identified a novel in-frame three base-pair deletion that may be responsible for the pathogenesis of atypical BENTA in a Chinese family. Our study expands the mutational spectrum of the
CARD11
gene and may be helpful in the understanding of diseases caused by
CARD11
mutations and the clinical management of BENTA. |
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Bibliography: | ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Review-3 content type line 23 ObjectType-Feature-5 ObjectType-Article-4 ObjectType-Report-1 Edited by: Andrew L. Snow, Uniformed Services University of the Health Sciences, United States Reviewed by: Saul Oswaldo Lugo Reyes, National Institute of Pediatrics, Mexico; Anne Helene Durandy, Institut National de la Santé et de la Recherche Médicale (INSERM), France This article was submitted to Primary Immunodeficiencies, a section of the journal Frontiers in Immunology These authors have contributed equally to this work |
ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2022.943027 |