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Identification and Characterization of a Germline Mutation in CARD11 From a Chinese Case of B Cell Expansion With NF-κB and T Cell Anergy

B cell expansion with NF-κB and T cell anergy (BENTA) is a rare primary immunodeficiency disorder caused by gain-of-function (GOF) mutations in the CARD11 gene. Affected patients present with persistent B cell lymphocytosis in early childhood paired with lymphadenopathy and splenomegaly. Until now o...

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Autores principales: Zhao, Peiwei, Meng, Qingjie, Huang, Yufeng, Zhang, Lei, Luo, Sukun, Zhang, Xiankai, Tan, Li, Zhou, Aifen, Xiong, Hao, He, Xuelian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453161/
https://www.ncbi.nlm.nih.gov/pubmed/34557185
http://dx.doi.org/10.3389/fimmu.2021.676386
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author Zhao, Peiwei
Meng, Qingjie
Huang, Yufeng
Zhang, Lei
Luo, Sukun
Zhang, Xiankai
Tan, Li
Zhou, Aifen
Xiong, Hao
He, Xuelian
author_facet Zhao, Peiwei
Meng, Qingjie
Huang, Yufeng
Zhang, Lei
Luo, Sukun
Zhang, Xiankai
Tan, Li
Zhou, Aifen
Xiong, Hao
He, Xuelian
author_sort Zhao, Peiwei
collection PubMed
description B cell expansion with NF-κB and T cell anergy (BENTA) is a rare primary immunodeficiency disorder caused by gain-of-function (GOF) mutations in the CARD11 gene. Affected patients present with persistent B cell lymphocytosis in early childhood paired with lymphadenopathy and splenomegaly. Until now only six activating mutations from 14 patients have been reported in CARD11. Here we report a patient from China with polyclonal B cell lymphocytosis and frequent infections in early life. A heterozygous mutation (c.377G>A, G126D) in exon 5 of CARD11 gene (NM_032415) was identified by whole exome sequencing. In vitro functional studies showed that the G126D mutation is associated with increased expression of CARD11 and NF-κB activation in Hela cells. Flow cytometry analysis indicated NK cell activity and CD107a degranulation of the patient were decreased. RNA sequencing analysis showed that a number of genes in NF-κB pathway increased while those involved in NK cell activity and degranulation were down-regulated. In summary, our work identified a de novo germline GOF mutation in CARD11 with functional evidence of BENTA.
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spelling pubmed-84531612021-09-22 Identification and Characterization of a Germline Mutation in CARD11 From a Chinese Case of B Cell Expansion With NF-κB and T Cell Anergy Zhao, Peiwei Meng, Qingjie Huang, Yufeng Zhang, Lei Luo, Sukun Zhang, Xiankai Tan, Li Zhou, Aifen Xiong, Hao He, Xuelian Front Immunol Immunology B cell expansion with NF-κB and T cell anergy (BENTA) is a rare primary immunodeficiency disorder caused by gain-of-function (GOF) mutations in the CARD11 gene. Affected patients present with persistent B cell lymphocytosis in early childhood paired with lymphadenopathy and splenomegaly. Until now only six activating mutations from 14 patients have been reported in CARD11. Here we report a patient from China with polyclonal B cell lymphocytosis and frequent infections in early life. A heterozygous mutation (c.377G>A, G126D) in exon 5 of CARD11 gene (NM_032415) was identified by whole exome sequencing. In vitro functional studies showed that the G126D mutation is associated with increased expression of CARD11 and NF-κB activation in Hela cells. Flow cytometry analysis indicated NK cell activity and CD107a degranulation of the patient were decreased. RNA sequencing analysis showed that a number of genes in NF-κB pathway increased while those involved in NK cell activity and degranulation were down-regulated. In summary, our work identified a de novo germline GOF mutation in CARD11 with functional evidence of BENTA. Frontiers Media S.A. 2021-09-07 /pmc/articles/PMC8453161/ /pubmed/34557185 http://dx.doi.org/10.3389/fimmu.2021.676386 Text en Copyright © 2021 Zhao, Meng, Huang, Zhang, Luo, Zhang, Tan, Zhou, Xiong 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
Meng, Qingjie
Huang, Yufeng
Zhang, Lei
Luo, Sukun
Zhang, Xiankai
Tan, Li
Zhou, Aifen
Xiong, Hao
He, Xuelian
Identification and Characterization of a Germline Mutation in CARD11 From a Chinese Case of B Cell Expansion With NF-κB and T Cell Anergy
title Identification and Characterization of a Germline Mutation in CARD11 From a Chinese Case of B Cell Expansion With NF-κB and T Cell Anergy
title_full Identification and Characterization of a Germline Mutation in CARD11 From a Chinese Case of B Cell Expansion With NF-κB and T Cell Anergy
title_fullStr Identification and Characterization of a Germline Mutation in CARD11 From a Chinese Case of B Cell Expansion With NF-κB and T Cell Anergy
title_full_unstemmed Identification and Characterization of a Germline Mutation in CARD11 From a Chinese Case of B Cell Expansion With NF-κB and T Cell Anergy
title_short Identification and Characterization of a Germline Mutation in CARD11 From a Chinese Case of B Cell Expansion With NF-κB and T Cell Anergy
title_sort identification and characterization of a germline mutation in card11 from a chinese case of b cell expansion with nf-κb and t cell anergy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453161/
https://www.ncbi.nlm.nih.gov/pubmed/34557185
http://dx.doi.org/10.3389/fimmu.2021.676386
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