Variants in genes involved in DNA or dNTP degradation (DNASE2(29–31), TREX1 and SAMHD1(32–36)) and RNA degradation (RNASEH2A, RNASEH2B and RNASEH2C(37)) (reviewed in 2018 (38)), are often associated with elevated levels of IFN–α and the emergence of familial chilblain lupus (FCL) (39) and childhood-onset SLE, as well as the classical interferonopathy Aicardi-Goutières syndrome (AGS) (24). Here, DNASE2 is linked to Aicardi-Goutieres syndrome.