Details of Disease

General Information of Disease (ID: DIS1NH4X)

• Disease Name: Aicardi-Goutieres syndrome
• Synonyms: Aicardi-Goutires syndrome; pseudotoxoplasmosis syndrome; AGS; encephalopathy, familial infantile, with calcification of basal ganglia and chronic cerebrospinal fluid lymphocytosis; Aicardi Goutieres syndrome; Cree encephalitis; encephalopathy with basal ganglia calcification; encephalopathy with intracranial calcification and chronic lymphocytosis of cerebrospinal fluid; Aicardi-Goutires Syndrome
• Disease Class: 5C55: Inborn purine/pyrimidine/nucleotide metabolism error
• Definition: Aicardi-Goutieres syndrome (AGS) is an inherited, subacute encephalopathy characterized by the association of basal ganglia calcification, leukodystrophy and cerebrospinal fluid (CSF) lymphocytosis.
• Disease Hierarchy:
  DISVY1TT: Leukodystrophy
  DISCPWH9: Autosomal recessive disease
  DISKP5TO: Type 1 interferonopathy of childhood
  DIS8I9FS: Hereditary disorder of connective tissue
  DISNGCMN: Inborn error of immunity
  DIS1NH4X: Aicardi-Goutieres syndrome
• ICD Code: ICD-11: ICD-11: 5C55.2
• Disease Identifiers:
  MONDO ID: MONDO_0018866
  MESH ID: C535607
  UMLS CUI: C0393591
  MedGen ID: 97953
  Orphanet ID: 51
  SNOMED CT ID: 230312006

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 2 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
C-176	DMKGSRZ	Investigative	Small molecular drug	[1]
C-178	DM4FEU8	Investigative	Small molecular drug	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 3 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
BACE2	TT69DB8	Strong	Genetic Variation	[2]
CLDN6	TTKSV48	Strong	Biomarker	[3]
TKTL1	TTNQ1J3	Strong	Biomarker	[4]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC17A6	DT5LHCR	Limited	Biomarker	[5]

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CYP7A1	DEDZRQ1	Strong	Altered Expression	[6]
LARS2	DEP7BTH	Strong	Biomarker	[7]

This Disease Is Related to 26 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
RPS19	OTBKGP48	Limited	Biomarker	[8]
STING1	OTDAP4G0	Limited	Altered Expression	[9]
IFIH1	OTZA2AHA	Supportive	Autosomal dominant	[10]
RNASEH2A	OT8G3G7K	Supportive	Autosomal dominant	[11]
RNASEH2B	OT8KHYFY	Supportive	Autosomal dominant	[11]
RNASEH2C	OTJL9ZRN	Supportive	Autosomal dominant	[11]
SAMHD1	OTBCIBC7	Supportive	Autosomal dominant	[11]
TREX1	OTQG7K12	Supportive	Autosomal dominant	[11]
ATRIP	OT78O9LF	Strong	Genetic Variation	[12]
CGAS	OTJYIXNB	Strong	Biomarker	[13]
CST7	OTQWZUVQ	Strong	Biomarker	[14]
HOOK2	OTPO4NQV	Strong	Genetic Variation	[15]
IFIT2	OTI4EOAR	Strong	Altered Expression	[16]
IGLON5	OTB94PY2	Strong	Biomarker	[17]
INPP5K	OTQFLQKA	Strong	Biomarker	[18]
LARS1	OT4557NF	Strong	Biomarker	[7]
MAF	OT1GR3IZ	Strong	Genetic Variation	[19]
NUDT11	OTFDXJA1	Strong	Genetic Variation	[2]
NUP35	OT6XNLQC	Strong	Biomarker	[20]
PLEKHM2	OT4ZYV73	Strong	Biomarker	[18]
RASD1	OT2BAJHK	Strong	Genetic Variation	[12]
RCOR1	OTREADPC	Strong	Genetic Variation	[21]
RNASET2	OTWY64L7	Strong	Biomarker	[22]
SNW1	OTKWG3PS	Strong	Biomarker	[18]
SPHKAP	OT5RHUYJ	Strong	Biomarker	[18]
ADAR	OTQNOHR8	Definitive	Autosomal recessive	[23]

References

• [1] Pharmacological modulation of nucleic acid sensors - therapeutic potential and persisting obstacles. Nat Rev Drug Discov. 2019 Nov;18(11):845-867.
• [2] Nonallelism for the audiogenic seizure prone (Asp1) and the aryl hydrocarbon receptor (Ahr) loci in mice.J Neurogenet. 1998 Nov;12(4):191-203. doi: 10.3109/01677069809108558.
• [3] Claudin-6 enhances cell invasiveness through claudin-1 in AGS human adenocarcinoma gastric cancer cells.Exp Cell Res. 2017 Jan 1;350(1):226-235. doi: 10.1016/j.yexcr.2016.11.025. Epub 2016 Dec 1.
• [4] Silencing of TKTL1 by siRNA inhibits proliferation of human gastric cancer cells in vitro and in vivo.Cancer Biol Ther. 2010 May 1;9(9):710-6. doi: 10.4161/cbt.9.9.11431. Epub 2010 May 8.
• [5] Audiogenic Seizures in the Fmr1 Knock-Out Mouse Are Induced by Fmr1 Deletion in Subcortical, VGlut2-Expressing Excitatory Neurons and Require Deletion in the Inferior Colliculus.J Neurosci. 2019 Dec 4;39(49):9852-9863. doi: 10.1523/JNEUROSCI.0886-19.2019. Epub 2019 Oct 30.
• [6] Negative feedback loop of cholesterol regulation is impaired in the livers of patients with Alagille syndrome.Clin Chim Acta. 2015 Feb 2;440:49-54. doi: 10.1016/j.cca.2014.10.034. Epub 2014 Oct 31.
• [7] Deleted chromosome 20 from a patient with Alagille syndrome isolated in a cell hybrid through leucine transport selection: study of three candidate genes.Mamm Genome. 1994 Nov;5(11):663-9. doi: 10.1007/BF00426072.
• [8] Repeated generalized seizures can produce calcified cardiac lesions in DBA/1 mice.Epilepsy Behav. 2019 Jun;95:169-174. doi: 10.1016/j.yebeh.2019.04.010. Epub 2019 May 4.
• [9] Inhibition of Cyclic GMP-AMP Synthase Using a Novel Antimalarial Drug Derivative in Trex1-Deficient Mice.Arthritis Rheumatol. 2018 Nov;70(11):1807-1819. doi: 10.1002/art.40559. Epub 2018 Sep 14.
• [10] Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling. Nat Genet. 2014 May;46(5):503-509. doi: 10.1038/ng.2933. Epub 2014 Mar 30.
• [11] Aicardi-Goutires Syndrome. 2005 Jun 29 [updated 2016 Nov 22]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [12] Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi-Goutieres syndrome. Am J Hum Genet. 2007 Apr;80(4):811-5. doi: 10.1086/513443. Epub 2007 Feb 19.
• [13] Expression of Cyclic GMP-AMP Synthase in Patients With Systemic Lupus Erythematosus.Arthritis Rheumatol. 2017 Apr;69(4):800-807. doi: 10.1002/art.40002. Epub 2017 Mar 7.
• [14] The Aicardi-Goutires syndrome. Molecular and clinical features of RNAse deficiency and microRNA overload.Mutat Res. 2011 Dec 1;717(1-2):99-108. doi: 10.1016/j.mrfmmm.2011.03.018. Epub 2011 Apr 15.
• [15] Synonymous mutations in RNASEH2A create cryptic splice sites impairing RNase H2 enzyme function in Aicardi-Goutires syndrome.Hum Mutat. 2013 Aug;34(8):1066-70. doi: 10.1002/humu.22336. Epub 2013 May 13.
• [16] Decreased IFIT2 Expression Promotes Gastric Cancer Progression and Predicts Poor Prognosis of the Patients.Cell Physiol Biochem. 2018;45(1):15-25. doi: 10.1159/000486219. Epub 2017 Dec 22.
• [17] Stiff person syndrome and other immune-mediated movement disorders - new insights.Curr Opin Neurol. 2016 Aug;29(4):496-506. doi: 10.1097/WCO.0000000000000351.
• [18] A precisely regulated gene expression cassette potently modulates metastasis and survival in multiple solid cancers.PLoS Genet. 2008 Jul 18;4(7):e1000129. doi: 10.1371/journal.pgen.1000129.
• [19] Further delineation of Aym-Gripp syndrome and use of automated facial analysis tool.Am J Med Genet A. 2018 Jul;176(7):1648-1656. doi: 10.1002/ajmg.a.38832.
• [20] Polystyrene nanoparticles internalization in human gastric adenocarcinoma cells.Toxicol In Vitro. 2016 Mar;31:126-36. doi: 10.1016/j.tiv.2015.11.006. Epub 2015 Nov 14.
• [21] Aicardi-Goutires Syndrome associated mutations of RNase H2B impair its interaction with ZMYM3 and the CoREST histone-modifying complex.PLoS One. 2019 Mar 19;14(3):e0213553. doi: 10.1371/journal.pone.0213553. eCollection 2019.
• [22] RNASET2-deficient leukoencephalopathy mimicking congenital CMV infection and Aicardi-Goutieres syndrome: a case report with a novel pathogenic variant.Orphanet J Rare Dis. 2019 Jul 26;14(1):184. doi: 10.1186/s13023-019-1155-9.
• [23] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.