In A-T, a critical kinase in DDRs, ATM, is defective and results in the accumulation of DSBs leading to the presence of cytosolic DNA (10, 123), while in AGS, mutations in the genes encoding products that process/degrade nucleic acids, such as TREX1 and RNAse H2, lead to cytosolic DNA accumulation and lethal autoimmunity in neonates (178, 226). Here, TREX1 is linked to Aicardi-Goutieres syndrome.