PRO136ALA CTLA4 Mutation

Cytotoxic T lymphocyte antigen–4 (CTLA-4) is an inhibitory receptor involved in the regulation of immune responses. Deficiency of Ctla4 in mice causes fatal multiorgan lymphocytic infiltration. We identified a heterozygous, missense c.406C>G, p.P136A mutation in CTLA4 in a CVID patient. This mutation is within the binding motif of CTLA-4 and is predicted to interfere with ligand binding. To test whether this mutation is causal in the phenotype of the patient, we will use CRISPR/Cas9-mediated genome editing to clone the mutation into a regulatory T cell-like cell line and use the edited cell line for functional studies.