Dominant negative CARD11 mutations: Beyond atopy Vivien Béziat, PhD, Emmanuelle Jouanguy, PhD, Anne Puel, PhD  Journal of Allergy and Clinical Immunology  Volume 143, Issue 4, Pages 1345-1347 (April 2019) DOI: 10.1016/j.jaci.2018.12.1006 Copyright © 2019 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 CARD11 in health and diseases. A, Schematic representation of CARD11, with its functional domains and reported germline mutations, including monoallelic gain-of-function (GOF) mutations found in patients with BENTA, biallelic LOF mutations found in patients with severe combined immunodeficiency (SCID), and monoallelic DN LOF mutations found in patients with combined immunodeficiency (CID) and atopy. DN LOF mutations reported for the first time by Dorjbal et al2 in this issue appear in boldface. B, Spectrum of clinical manifestations found in patients according to CARD11 functional activity. C, Frequency of all CARD11 alleles found in gnomAD or in patients with CID and atopy by means of combined annotation dependent depletion (CADD) score; the dotted line indicates the mutation significance cutoff (MSC). Variants functionally tested in vitro for their effect on NF-κB signaling are indicated. Enhanced, Increase in signaling; Hypo, hypomorphic; Neutral, no effect; NR, alleles never reported in gnomAD. Variants reported in gnomAD are classified as missense or “predicted LOF” (essential splicing, stop codon, or frameshift mutations). het, Variants reported only in the heterozygous state; hom, variants reported at least once at the homozygous state. Note: R974C, E766D, and D1152N, which were found in this study, have each been found in the homozygous state in 1 subject reported in the GnomAD database. Journal of Allergy and Clinical Immunology 2019 143, 1345-1347DOI: (10.1016/j.jaci.2018.12.1006) Copyright © 2019 American Academy of Allergy, Asthma & Immunology Terms and Conditions