In our study, we enrolled two patients carrying CTLA4 mutations; these patients had an initial diagnosis of CVID, fulfilling the diagnostic criteria of the disease (low immunoglobulin levels, absence of antibody responses to vaccines, and exclusion of secondary causes of immunodeficiency), exhibiting also lymphoproliferation and autoimmune manifestations [21], and they received replacement treatment for years before the demonstration of CTLA4 mutations. The gene discussed is CTLA4; the disease is immune system disorder.