Aicardi-Goutieres syndrome: from patients to genes and beyond

Clin Genet. 2012 May;81(5):413-20. doi: 10.1111/j.1399-0004.2011.01825.x. Epub 2012 Jan 8.


Aicardi-Goutières syndrome (AGS) is a hereditary neurodegenerative disorder characterized mainly by early onset progressive encephalopathy, concomitant with an increase in interferon-α levels in the cerebrospinal fluid. Although it was initially mistaken for intrauterine viral infections, AGS has now been genetically attributed to a lack of adequate processing of cellular nucleic acid debris, which culminates in the perpetual trigger of the innate and acquired immune responses. Although the exact mechanisms governing AGS are not fully understood, significant strides have been recently achieved in better characterizing the disorder and the molecular functions of the five known proteins found mutated in AGS. Studies have now uncovered that AGS is tightly linked with the predisposition to other autoimmune disorders such as familial chilblain lupus and systemic lupus erythematosus. Moreover, at least two of the proteins mutated in AGS, namely TREX1 and SAMHD1, also seem to have antagonistic roles in safeguarding humans from human immunodeficiency virus (HIV) infections. We hereby synthesize the current developments into the greater framework of AGS and suggest that a better understanding of AGS might help usher a better treatment not only for some autoimmune disorders but also possibly for patients suffering from HIV infections, too.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / complications
  • Autoimmune Diseases of the Nervous System / complications
  • Autoimmune Diseases of the Nervous System / etiology*
  • Autoimmune Diseases of the Nervous System / genetics
  • Brain Diseases / complications
  • Humans
  • Metabolic Diseases / complications
  • Nervous System Malformations / complications
  • Nervous System Malformations / etiology*
  • Nervous System Malformations / genetics
  • Vascular Diseases / complications

Supplementary concepts

  • Aicardi-Goutieres syndrome