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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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Autores principales: Zhao, Peiwei, Hu, Yanqiu, Sun, Dongming, Meng, Qingjie, Zhang, Lei, Zhang, Xiankai, Tan, Li, Zhang, Yong, Ding, Yan, He, Xuelian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530255/
https://www.ncbi.nlm.nih.gov/pubmed/36203613
http://dx.doi.org/10.3389/fimmu.2022.943027
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author Zhao, Peiwei
Hu, Yanqiu
Sun, Dongming
Meng, Qingjie
Zhang, Lei
Zhang, Xiankai
Tan, Li
Zhang, Yong
Ding, Yan
He, Xuelian
author_facet Zhao, Peiwei
Hu, Yanqiu
Sun, Dongming
Meng, Qingjie
Zhang, Lei
Zhang, Xiankai
Tan, Li
Zhang, Yong
Ding, Yan
He, Xuelian
author_sort Zhao, Peiwei
collection PubMed
description 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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spelling pubmed-95302552022-10-05 A novel CARD11 germline mutation in a Chinese patient of B cell expansion with NF-κB and T cell anergy (BENTA) and literature review Zhao, Peiwei Hu, Yanqiu Sun, Dongming Meng, Qingjie Zhang, Lei Zhang, Xiankai Tan, Li Zhang, Yong Ding, Yan He, Xuelian Front Immunol Immunology 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. Frontiers Media S.A. 2022-09-20 /pmc/articles/PMC9530255/ /pubmed/36203613 http://dx.doi.org/10.3389/fimmu.2022.943027 Text en Copyright © 2022 Zhao, Hu, Sun, Meng, Zhang, Zhang, Tan, Zhang, Ding and He https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zhao, Peiwei
Hu, Yanqiu
Sun, Dongming
Meng, Qingjie
Zhang, Lei
Zhang, Xiankai
Tan, Li
Zhang, Yong
Ding, Yan
He, Xuelian
A novel CARD11 germline mutation in a Chinese patient of B cell expansion with NF-κB and T cell anergy (BENTA) and literature review
title A novel CARD11 germline mutation in a Chinese patient of B cell expansion with NF-κB and T cell anergy (BENTA) and literature review
title_full A novel CARD11 germline mutation in a Chinese patient of B cell expansion with NF-κB and T cell anergy (BENTA) and literature review
title_fullStr A novel CARD11 germline mutation in a Chinese patient of B cell expansion with NF-κB and T cell anergy (BENTA) and literature review
title_full_unstemmed A novel CARD11 germline mutation in a Chinese patient of B cell expansion with NF-κB and T cell anergy (BENTA) and literature review
title_short A novel CARD11 germline mutation in a Chinese patient of B cell expansion with NF-κB and T cell anergy (BENTA) and literature review
title_sort novel card11 germline mutation in a chinese patient of b cell expansion with nf-κb and t cell anergy (benta) and literature review
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530255/
https://www.ncbi.nlm.nih.gov/pubmed/36203613
http://dx.doi.org/10.3389/fimmu.2022.943027
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