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J Clin Immunol. 2020 Jan 2. doi: 10.1007/s10875-019-00729-x. [Epub ahead of print]

A Novel, Heterozygous Three Base-Pair Deletion in CARD11 Results in B Cell Expansion with NF-κB and T Cell Anergy Disease.

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Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, West Midlands, B15 2TT, UK.
Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Department of Clinical Immunology, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
NIHR Oxford Biomedical Research Centre, Oxford, UK.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.


Germline gain-of-function mutations in CARD11 lead to the primary immunodeficiency, B cell expansion with NF-κB, and T cell anergy (BENTA). Herein, we report the case of a girl, presenting at 2 years of age with lymphocytosis and splenomegaly in whom a novel, in-frame, three base pair deletion in CARD11 was identified resulting in the deletion of a single lysine residue (K215del) from the coiled-coil domain. In vitro functional assays demonstrated that this variant leads to a subtle increase in baseline NF-κB signaling and impaired proliferative responses following T cell receptor and mitogenic stimulation. Previously reported immunological defects associated with BENTA appear mild in our patient who is now 6 years of age; a B cell lymphocytosis and susceptibility to upper respiratory tract infections persist; however, she has broad, sustained responses to protein-polysaccharide conjugate vaccines and displays normal proliferative responses to ex vivo T cell stimulation.


BENTA; CARD11; Primary immunodeficiency


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