Background and Aims: Caspase activation and recruitment domain 11 (CARD11) encodes a scaffold protein in lymphocytes that links antigen receptor engagement with downstream signaling to NFκB, c-Jun N-terminal kinase, and mTORC1. This case report describes the unusual clinical presentation of an adult with a dominant negative (DN) monoallelic mutation in CARD11.
Methods: Analysis of medical records, laboratory results, tissue biopsies and gene sequencing information.
Results: Our patient was referred to us for the consideration of allogeneic HSCT at the age of 40 years. His history dated back to childhood with early onset atopy, multiple food allergies and eczema. At the age of 29 years he presented with multiple intrathoracic and hepatic tumours, which on biopsy were shown to be EBV-associated leiomyomas. Immunology investigations demonstrated a mild reduction in B cells with normal total T and NK cells, preserved immunoglobulin levels but a suboptimal response to polysaccharide pneumococcal vaccine. Targeted chip sequencing identified a previously described monoallelic missense mutation (c.214C>G; NM_032415.4:c.214C>G, R72G) with dominant negative effect. The previous cases were characterised in two patients by alopecia, joint pain, oral ulcers, pulmonary TB; and in a third by persistent skin infections (VZV, HPV), EBV viremia, progressive B-cell lymphopenia and frequent osteomyelitis.
Conclusion: EBV-associated leiomyomas are a rare complication of PID, described in less than 20 cases to date with a range of underlying genetic causes. To our knowledge, this is the first case of EBV leiomyomatosis in CARD11 related PID and expands the spectrum of clinical phenotype of CARD11 mutations.