CARD11 MUTATION IN A PATIENT WITH VERY EARLY ONSET IBD AND IMMUNODEFICIENCY

Abstract

<h3>Background</h3> Caspase activation and recruitment domain 11 (CARD11) is a lymphocyte-specific scaffolding protein which plays are role in signaling through both the NF-κB and mTOR signaling cascades important in B- and T-cell function. Various mutations in the <i>CARD11</i> gene cause several different phenotypes. Heterozygous dominant negative (DN) mutations can result in variable immune deficiency, with associated predisposition for atopy. Gain-of-function mutations causes BENTA (B-cell Expansion with NF-κB and T-cell Anergy) disease. While most patients with <i>CARD11</i> mutations are diagnosed in childhood, some milder phenotypes can result delayed diagnosis. <h3>Case Description</h3> A 4-year-old female was diagnosed with VEO-IBD (ulcerative colitis). She had a history of recurrent infections since 8-months-old including infantile pneumonia, otitis media, MRSA skin abscesses, molluscum contagiosum and cutaneous warts, as well as eczema, allergic rhinitis and asthma. Immunologic workup revealed inadequate response to polysaccharide vaccine . Lymphocyte proliferation was decreased to <i>Candida</i> and Tetanus antigens. Despite IVIG infusions, with control of sinopulmonary infections but her viral cutaneous infections worsened. Her IBD was unresponsive to anti-TNF therapy, but improved with vedolizumab. Primary immunodeficiency diseases panel (426 gene) revealed a heterozygous <i>CARD11</i> VUS (c.223C>T, p.Arg75Trp). The same variant was present in her father, who was symptomatic with molluscum contagiousum and aphthous ulcers. <h3>Discussion</h3> We present a unique CARD11 mutation in the coiled-coil domain region of the CARD11 gene is suspected of causing a DN phenotype, including recurrent bacterial sinopulmonary and viral infections, atopic features, and VEO-IBD. In vitro functional studies of this mutation are in process to confirm pathogenicity of this variant.