Loss-of-function (LOF) variants in deoxyribonuclease 2 (DNASE2) and three-prime repair exonuclease 1 (TREX1) result in defective nucleic acid degradation, causing Aicardi–Goutières syndrome, SLE and familial chilblain lupus. The gene discussed is TREX1; the disease is familial chilblain lupus.