A number of the genes associated with type I interferonopathy and AGS code for nucleases, including TREX1, RNASEH2A, RNASEH2B, RNASEH2C, DNASE2, and SKIV2L. Hypomorphic variants of these genes lead to defects in nuclease activity and thus the accumulation of self nucleic acids and erroneous activation of anti-viral nucleic acid immune sensing receptors12,16. This evidence concerns the gene TREX1 and Aicardi-Goutieres syndrome.