Aicardi-Goutieres syndrome

Aicardi-Goutieres Syndrome (AGS) is an autosomal recessive encephalopathy characterized by basal ganglia and white matter calcification in the presence of chronic cerebrospinal fluid lymphocytosis, and a raised level of cerebrospinal fluid IFNalpha. There is progressive neurological dysfunction resulting in a failure of development of expected physical and social skills. AGS presents in infancy and is lethal in ~40% of cases. It can be caused by mutations in the following genes, TREX1, RNaseH2 and SAMHD1 that lead to excessive intracellular accumulation of DNA and abnormal type I IFN metabolism.

Immune system disease

(AGS1) TREX1 [HSA:11277] [KO:K10790]
(AGS2) RNASEH2B [HSA:79621] [KO:K10744]
(AGS3) RNASEH2C [HSA:84153] [KO:K10745]
(AGS4) RNASEH2A [HSA:10535] [KO:K10743]
(AGS5) SAMHD1 [HSA:25939] [KO:K22544]
(AGS6) ADAR [HSA:103] [KO:K12968]
(AGS7) IFIH1 [HSA:64135] [KO:K12647]

PMID:19442247

Lindahl T, Barnes DE, Yang YG, Robins P

Biochemical properties of mammalian TREX1 and its association with DNA replication and inherited inflammatory disease.

Biochem Soc Trans 37:535-8 (2009)
DOI:10.1042/BST0370535

PMID:19525956

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Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response.

Nat Genet 41:829-32 (2009)
DOI:10.1038/ng.373

PMID:18583934

Kavanagh D, Spitzer D, Kothari PH, Shaikh A, Liszewski MK, Richards A, Atkinson JP

New roles for the major human 3'-5' exonuclease TREX1 in human disease.

Cell Cycle 7:1718-25 (2008)
DOI:10.4161/cc.7.12.6162

PMID:18406216

O'Driscoll M

TREX1 DNA exonuclease deficiency, accumulation of single stranded DNA and complex human genetic disorders.

DNA Repair (Amst) 7:997-1003 (2008)
DOI:10.1016/j.dnarep.2008.02.010

PMID:18693262

Rigby RE, Leitch A, Jackson AP

Nucleic acid-mediated inflammatory diseases.

Bioessays 30:833-42 (2008)
DOI:10.1002/bies.20808

PMID:18724932

Stetson DB, Ko JS, Heidmann T, Medzhitov R

Trex1 prevents cell-intrinsic initiation of autoimmunity.

Cell 134:587-98 (2008)
DOI:10.1016/j.cell.2008.06.032

PMID:19808788

Crow YJ, Rehwinkel J

Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity.

Hum Mol Genet 18:R130-6 (2009)
DOI:10.1093/hmg/ddp293

PMID:18343173

Stephenson JB

Aicardi-Goutieres syndrome (AGS).

Eur J Paediatr Neurol 12:355-8 (2008)
DOI:10.1016/j.ejpn.2007.11.010

PMID:18422679

Crow YJ, Livingston JH

Aicardi-Goutieres syndrome: an important Mendelian mimic of congenital infection.

Dev Med Child Neurol 50:410-6 (2008)
DOI:10.1111/j.1469-8749.2008.02062.x

PMID:25243380

Crow YJ, Zaki MS, Abdel-Hamid MS, Abdel-Salam G, Boespflug-Tanguy O, Cordeiro NJ, Gleeson JG, Gowrinathan NR, Laugel V, Renaldo F, Rodriguez D, Livingston JH, Rice GI

Mutations in ADAR1, IFIH1, and RNASEH2B presenting as spastic paraplegia.

Neuropediatrics 45:386-93 (2014)
DOI:10.1055/s-0034-1389161