FIGURE 3.

Pathogenic mutations in Aicardi–Goutières syndrome. Mutations in genes in at least six distinct loci are able give rise to the constellation of symptoms that defines Aicardi–Goutières syndrome. Four of these (AGS2, AGS3, AGS4, and AGS6) are in genes that encode RNA-metabolizing proteins. The remaining two that have been identified (AGS1 and AGS5) are also in enzymes that have roles in nucleic acid metabolism. Deficiencies in any one of these enzymes are thought to result in the accumulation of endogenous nucleic acids that are sensed as “non-self” by Toll-like receptors, that in turn activate innate inflammatory pathways (Crow and Rehwinkel, 2009).