{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T04:12:22Z","timestamp":1777349542086,"version":"3.51.4"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Germline gain-of-function (GOF) mutations in the <jats:italic>CARD11<\/jats:italic> gene lead to a rare primary immunodeficiency disease known as B cell expansion with NF-\u03baB 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 <jats:italic>CARD11<\/jats:italic> 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. <jats:italic>In vitro<\/jats:italic> functional analysis demonstrated that this variant decreased the expression level of the CARD11 protein and activated the NF-\u03baB signal pathway, leading to a higher expression of several NF-\u03baB 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 <jats:italic>CARD11<\/jats:italic>. 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 <jats:italic>CARD11<\/jats:italic> gene and may be helpful in the understanding of diseases caused by <jats:italic>CARD11<\/jats:italic> mutations and the clinical management of BENTA.<\/jats:p>","DOI":"10.3389\/fimmu.2022.943027","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T05:09:15Z","timestamp":1663650555000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["A novel CARD11 germline mutation in a Chinese patient of B cell expansion with NF-\u03baB and T cell anergy (BENTA) and literature 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