Patients with activating mutations in PIK3R1 leading to an increased PI3Kδ activity also have primary immunodeficiency (67, 69, 116–123), and many studies, including large cohort studies, have defined new mutations in PIK3CD leading to activated PI3K delta syndrome (APDS) and expanded the phenotype of disease (64, 66, 67, 124–131). Here, PIK3CD is linked to activated PI3K-delta syndrome.