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Gain-of-function mutations in IFIH1 were identified in Aicardi-Goutieres syndrome (AGS), a rare neuroimmunological disorder associated with elevated levels of type I interferon and characterized by leucoencephalopathy, brain atrophy and intracranial calcifications leading to profound intellectual disability, spasticity and dystonia. IFIH1 functions as an intracellular innate immune receptor that senses viral nucleic acids and leads to the induction of type I interferon and proinflammatory cytokines.

Gain-of-function mutation in IFIH1 can cause both aicardi-goutières syndrome and systemic lupus erythematosus with IgA-deficiency