They provided proof that these mutations were autosomal dominant gain-of-function (GOF) and lead to increased PI3Kδ signaling responsible for a lymphoproliferation-associated primary combined immunodeficiency syndrome (Activated PI3-kinase-δ syndrome (APDS; also referred as APDS1); OMIM: # 615513; immunodeficiency 14; IMD14; also referred as p110-delta-activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency; (PASLI also referred as PASLI-CD) (8, 9). The gene discussed is PIK3CD; the disease is Down syndrome.