A novel, heterozygous three base-pair deletion in CARD11 results in B cell expansion with NF-κB and T cell anergy disease

Journal article : Letter

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.

Authors: Shields, A; Bauman, B; Hargreaves, C; Pollard, A; Snow, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer nature
• Journal: https://link.springer.com/journal/10875
• Volume: 40
• Issue: 2020
• Pages: 406-411
• Publication date: 2020-01-02
• Acceptance date: 2019-11-26
• DOI: 10.1007/s10875-019-00729-x
• EISSN: 1573-2592
• ISSN: 0271-9142
• Pmid: 31897776
• Language: English
• Keywords: primary immunodeficiency; CARD11; BENTA; FFR
• Subtype: Letter