Abstract: Objective：To report and summarize the clinical and immune features of two patients with CARD11  mutations, which are not located in CARD domain or CC domain of the gene.
Methods：Two atypical CARD11  mutation patients were enrolled, and their clinical and immune features were summarized. The mutations were tested by whole exon sequencing and confirmed by Sanger sequencing. Flow cytometry was used to figure out the immune phenotypes, while in vitro experiments were performed to detect the pathogenicity and pathogenic mechanism of the mutations.
Results：The two patients had recurrent respiratory infection and allergic diseases. Patient 1 (P1) presented with recurrent tonsillitis, bronchopneumonia, allergic rhinitis and occasional abdominal pain or joint pain together with fever. Patient 2 (P2) presented with recurrent upper respiratory infection，occasional atopic dermatitis and allergic conjunctivitis. Both of the two patients had heterozygous mutation in the gene of CARD11 . The mutation sites were c.2542C>T （p.R848C）for P1 and c.2036A>T（p.Q679L）for P2. c.2542C>T was reported in 2019 and c.2036A>T had not been reported before. The two mutant CARD11  proteins showed less stimulation of the NF-κB signal pathway compared with WT CARD11  protein when overexpressed in 293T cells, which indicates that the mutations would lead to loss of function(LOF).
 Conclusion：The characteristics of this novel CARD11  mutation are different from those of mutations in typical sites, which enriches the clinical and immune features of CARD11  deficiency.

Key words: CARD11 deficiency, Immunodeficiency, Immunodeficiency 11B with atopic dermatitis