To test whether RVCL TREX1 causes DNA damage in human cells, we established an inducible Flp-in expression system for TREX1 variants associated with several human diseases, including RVCL, systemic lupus erythematosus (SLE), Aicardi-Goutières syndrome (AGS), and familial chilblain lupus (FCL) (Fig. 2a and Supplementary Fig. 1b–c). This evidence concerns the gene TREX1 and familial chilblain lupus.