Aicardi-Goutières syndrome (AGS) is an autosomal-recessive encephalopathy in children that is characterized by mutations in numerous nucleic acid repair enzymes and elevated IFN levels.
Excessive release of type I IFNs through STING-dependent mechanisms has emerged as a central driver of several interferonopathies, including systemic lupus erythematosus (SLE), Aicardi-Goutières syndrome (AGS), and stimulator of IFN genes-associated vasculopathy with onset in infancy (SAVI).
In humans, loss of function mutations in the SAMHD1 (AGS5) gene cause a severe form of Aicardi-Goutières syndrome (AGS), an inherited inflammatory-mediated encephalopathy characterized by increased type I IFN activity and upregulation of IFN-stimulated genes (ISGs).
These results explain why loss of ADARA1 causes IFN induction and also indicates a mechanism for the involvement of ADAR1 in autoimmune diseases such as Aicardi-Goutières syndrome.