Impairment of central tolerance by inherited defects of thymic development leads to syndromes including the autoimmune lymphoproliferative syndromes (ALPS), caused by failure of the extrinsic activation-induced cell death pathways (mutations in FAS, FASLG, and FADD), and autoimmune polyglandular syndrome (APS) 1, caused by mutations in AIRE. This evidence concerns the gene FAS and autoimmune lymphoproliferative syndrome.