Specific and overlapping features of monogenic type I interferonopathies. In the broadest sense, CNS and skin disease are the most common features of the type I interferonopathies. Discrete neurological phenotypes associated with mutations in AGS-associated genes include “nonsyndromic” spastic paraparesis (RNASEH2B, ADAR1, and IFIH1 [Crow et al., 2014]) and bilateral striatal necrosis (ADAR1 [Livingston et al., 2014]). Glaucoma is a common feature of AGS (Crow et al., 2015) and is also seen in the Singleton-Merton syndrome phenotype associated with gain-of-function mutations in IFIH1 (Bursztejn et al., 2015; Rutsch et al., 2015) and DDX58 (RIG-I [Jang et al., 2015]). SLE (lupus) is most frequently associated with mutations in ACP5 (An et al., 2016; Briggs et al., 2016) and C1q (Lood et al., 2009; Santer et al., 2010). Malignancy has only been reported in the context of SAMHD1 (Clifford et al., 2014; Merati et al., 2015). Lung inflammation is so far restricted to patients with mutations in TMEM173 (STING; Liu et al., 2014; Clarke et al., 2016; Picard et al., 2016). The phenotypes associated with mutations in POLA1 and SKIV2L appear distinct.