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.
Journal article
2020-02-01T00:00:00+00:00
40
406 - 411
5
Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, West Midlands, B15 2TT, UK. a.m.shields@bham.ac.uk.
B-Lymphocytes, T-Lymphocytes, Cells, Cultured, Humans, Lymphocytosis, Immunologic Deficiency Syndromes, Guanylate Cyclase, NF-kappa B, Lymphocyte Activation, Cell Proliferation, Clonal Anergy, Sequence Deletion, Base Pairing, Heterozygote, Child, Child, Preschool, Infant, Female, CARD Signaling Adaptor Proteins