For example, Aicardi-Goutières syndrome and familial chilblain lupus are caused by mutations in three-prime repair exonuclease 1 (TREX1), ribonuclease H2 (RNaseH2) or sterile alpha motif domain and HD domain-containing protein 1(SAMHD1) that result in accumulation of genomic self-DNA in the cytoplasm via different mechanisms and therefore trigger cGAS activation and autoinflammation (reviewed in72). Here, TREX1 is linked to familial chilblain lupus.