Mutations in ACP5 and SAMHD1 are known to drive the pathogenesis of SPENCD and AGS, both of which are monogenic interferon diseases characterized by increased type I IFN signaling leading to vasculopathy, autoinflammation, and SLE-like disease (8, 23, 24). Here, SAMHD1 is linked to Aicardi-Goutieres syndrome.