AGS
MCID: ACR001
MIFTS: 63

Aicardi-Goutieres Syndrome (AGS)

Categories: Blood diseases, Bone diseases, Genetic diseases, Immune diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Aicardi-Goutieres Syndrome

MalaCards integrated aliases for Aicardi-Goutieres Syndrome:

Name: Aicardi-Goutieres Syndrome 12 74 20 43 53 58 36 15 39 71
Aicardi Goutieres Syndrome 20 43 29 6
Encephalopathy with Basal Ganglia Calcification 20 43 58
Cree Encephalitis 12 20 43
Encephalopathy with Intracranial Calcification and Chronic Lymphocytosis of Cerebrospinal Fluid 20 58
Pseudotoxoplasmosis Syndrome 20 43
Aicardi-Goutières Syndrome 25 43
Ags 20 43
Encephalopathy, Familial Infantile, with Calcification of Basal Ganglia and Chronic Cerebrospinal Fluid Lymphocytosis 20
Familial Infantile Encephalopathy with Intracranial Calcification and Chronic Cerebrospinal Fluid Lymphocytosis 43
Aicardi-Goutieres Syndrome 1 71

Characteristics:

Orphanet epidemiological data:

58
aicardi-goutieres syndrome
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: adolescent,late childhood;

Classifications:

Orphanet: 58  
Rare neurological diseases
Rare systemic and rhumatological diseases
Rare immunological diseases


Summaries for Aicardi-Goutieres Syndrome

MedlinePlus Genetics : 43 Aicardi-Goutières syndrome is a disorder that mainly affects the brain, the immune system, and the skin.Most newborns with Aicardi-Goutières syndrome do not show any signs or symptoms of the disorder. However, about 20 percent are born with a combination of features that include an enlarged liver and spleen (hepatosplenomegaly), elevated blood levels of liver enzymes, a shortage of blood cells called platelets that are needed for normal blood clotting (thrombocytopenia), and neurological abnormalities. While this combination of signs and symptoms is typically associated with the immune system's response to a viral infection that is present at birth (congenital), no actual infection is found in these infants. For this reason, Aicardi-Goutières syndrome is sometimes referred to as a "mimic of congenital infection."Within the first year of life, most individuals with Aicardi-Goutières syndrome experience an episode of severe brain dysfunction (encephalopathy), typically lasting for several months. During this encephalopathic phase of the disorder, affected babies are usually extremely irritable and do not feed well. They may develop intermittent fevers in the absence of infection (sterile pyrexias) and may have seizures. They stop developing new skills and begin losing skills they had already acquired (developmental regression). Growth of the brain and skull slows down, resulting in an abnormally small head size (microcephaly). In this phase of the disorder, white blood cells and other immune system molecules associated with inflammation can be detected in the cerebrospinal fluid, which is the fluid that surrounds the brain and spinal cord (central nervous system). These abnormal findings are consistent with inflammation and tissue damage in the central nervous system.The encephalopathic phase of Aicardi-Goutières syndrome causes permanent neurological damage that is usually severe. Medical imaging reveals loss of white matter in the brain (leukodystrophy). White matter consists of nerve fibers covered by myelin, which is a substance that protects nerves and insures rapid transmission of nerve impulses. Affected individuals also have abnormal deposits of calcium (calcification) in the brain. As a result of this neurological damage, most people with Aicardi-Goutières syndrome have profound intellectual disability. They also have muscle stiffness (spasticity); involuntary tensing of various muscles (dystonia), especially those in the arms; and weak muscle tone (hypotonia) in the torso.Some people with Aicardi-Goutières syndrome have features characteristic of autoimmune disorders, which occur when the immune system malfunctions and attacks the body's own systems and organs. Some of these features overlap with those of another disorder called systemic lupus erythematosus (SLE). A feature of SLE that also occurs in about 40 percent of people with Aicardi-Goutières syndrome is a skin problem called chilblains. Chilblains are painful, itchy skin lesions that are puffy and red, and usually appear on the fingers, toes, and ears. They are caused by inflammation of small blood vessels, and may be brought on or made worse by exposure to cold. Vision problems, joint stiffness, and mouth ulcers are other features that can occur in both disorders.As a result of the severe neurological problems usually associated with Aicardi-Goutières syndrome, most people with this disorder do not survive past childhood. However, some affected individuals who develop the condition later or have milder neurological problems live into adulthood.

MalaCards based summary : Aicardi-Goutieres Syndrome, also known as aicardi goutieres syndrome, is related to aicardi-goutieres syndrome 1 and aicardi-goutieres syndrome 3, and has symptoms including seizures and petechiae of skin. An important gene associated with Aicardi-Goutieres Syndrome is SAMHD1 (SAM And HD Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase 1), and among its related pathways/superpathways are Cytosolic DNA-sensing pathway and DNA replication. The drugs Adenosine and Emtricitabine have been mentioned in the context of this disorder. Affiliated tissues include brain, liver and spleen, and related phenotypes are global developmental delay and arrhinencephaly

Disease Ontology : 12 A syndrome that is a genetically heterogeneous encephalopathy characterized in its most severe form by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic cerebrospinal fluid lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infections.

GARD : 20 Aicardi-Goutieres syndrome is an inherited disease that mainly affects the brain, immune system, and the skin. Loss of white matter in the brain (leukodystrophy) and abnormal deposits of calcium (calcification) in the brain leads to an early-onset severe brain dysfunction (encephalopathy) that usually results in severe intellectual and physical disability. Additional symptoms may include epilepsy, painful, itchy skin lesion (chilblains), vision problems, and joint and muscle stiffness (spasticity), involuntary muscle twisting and contractions (dystonia), and weak muscle tone (hypotonia) in the torso. Other signs and symptoms may include a very small head (microcephaly), presence of white blood cells and other sign of inflammation in the cerebrospinal fluid, which is the fluid that surrounds the brain and spinal cord (central nervous system). Symptoms usually progress over several months before the disease course stabilizes. There are several types of Aicardi-Goutieres syndrome, depending on the gene that causes the condition: TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR and IFIH1, genes. Most cases are inherited in an autosomal recessive pattern, although rare autosomal dominant cases have been reported. Treatment is symptomatic and supportive. The prognosis depends mainly on the severity neurologic problems and in the age of onset of these problems.

NINDS : 53 Aicardi-Goutieres syndrome (AGS) is an inherited encephalopathy that affects newborn infants and usually results in severe mental and physical handicap. There are two forms of the syndrome: an early-onset form that is severe, and a late-onset form that has less impact upon neurological function. The early-onset form affects about 20 percent of all babies who have AGS. These infants are born with neurological and liver abnormalities, such as enlargement of the liver and spleen and elevated liver enzymes. Their jittery behavior and poor feeding ability mimic congenital viral infection. Babies with later-onset AGS begin having symptoms after the first weeks or months of normal development, which appear as a progressive decline in head growth, weak or stiffened muscles (spasticity), and cognitive and developmental delays that range from moderate to severe. Symptoms last for several months, and include irritability, inconsolable crying, intermittent fever, seizures, and loss of developmental skills. Children may also have puffy swelling on the fingers, toes, and ears that resemble chilblains. A number of children have a noticeable startle reaction to sudden noise. For babies with the later-onset form, as symptoms lessen, there is no further worsening of the disease. AGS is difficult to diagnose since many of the symptoms are similar to those of other disorders. Diagnosis is made based on the clinical symptoms of the disease, as well as characteristic brain abnormalities that can be seen in an MRI brain scan. Cerebrospinal fluid (CSF), taken using a "spinal tap," can also be tested for increased levels of a specific immune system cell (a lymphocyte), which indicates a condition known as chronic lymphocytosis. These cells are normally only elevated during infection, so that lymphocytosis without evidence of infection can be used as an indicator of AGS. CSF may also be tested for elevated levels of a substance known as interferon-gamma, which can also support a diagnosis of AGS. The mutations of four different genes are associated with AGS: Aicardi-Goutieres syndrome-1 (AGS1) and AGS5 (an autosomal dominant form) are caused by a mutation in the TREX1 gene, AGS2 is caused by a mutation in the RNASEH2B gene, AGS3 is caused by a mutation in the RNASEH2C gene, AGS4 is caused by a mutation in the RNASEH2A gene. Most cases of AGS are inherited in an autosomal recessive manner, which means that both parents of a child with AGS must carry a single copy of the defective gene responsible for the disease. Parents do not have any symptoms of disease, but with every child they have together, there is a one in four chance that the baby will receive two copies of the defective gene and inherit AGS. NOTE: AGS is distinct from the similarly named Aicardi syndrome (characterized by absence of a brain structure (corpus callosum), and spinal, skeletal, and eye abnormalities).

KEGG : 36 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.

Wikipedia : 74 Aicardi-Goutières syndrome (AGS), which is completely distinct from the similarly named Aicardi... more...

GeneReviews: NBK1475

Related Diseases for Aicardi-Goutieres Syndrome

Diseases in the Aicardi-Goutieres Syndrome family:

Aicardi-Goutieres Syndrome 1 Aicardi-Goutieres Syndrome 2
Aicardi-Goutieres Syndrome 3 Aicardi-Goutieres Syndrome 4
Aicardi-Goutieres Syndrome 5 Aicardi-Goutieres Syndrome 6
Aicardi-Goutieres Syndrome 7

Diseases related to Aicardi-Goutieres Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 232)
# Related Disease Score Top Affiliating Genes
1 aicardi-goutieres syndrome 1 33.8 TREX1 SAMHD1 RNASEH2B RNASEH2A ATRIP-TREX1 ATRIP
2 aicardi-goutieres syndrome 3 33.6 RNASEH2C KAT5
3 aicardi-goutieres syndrome 5 33.6 TLDC2 SAMHD1
4 aicardi-goutieres syndrome 2 33.6 RNASEH2B-AS1 RNASEH2B
5 aicardi-goutieres syndrome 4 33.5 RNASEH2A LOC117038795
6 familial chilblain lupus 31.5 TREX1 STING1 SAMHD1
7 microcephaly 31.5 TREX1 SAMHD1 RNASEH2C RNASEH2B RNASEH2A IFIH1
8 leukodystrophy 31.4 TREX1 SAMHD1 RNASEH2C RNASEH2B RNASEH2A ADAR
9 chilblain lupus 1 31.4 TREX1 STING1 SAMHD1 RNASEH2C RNASEH2B RNASEH2A
10 dyschromatosis symmetrica hereditaria 31.3 RNASEH2C RNASEH2B RNASEH2A ADAR
11 type 1 interferonopathy 30.9 TREX1 SAMHD1
12 chilblain lupus 2 30.9 TLDC2 SAMHD1
13 dystonia 30.8 SAMHD1 RNASEH2C RNASEH2B RNASEH2A ADAR
14 basal ganglia calcification 30.4 RNASEH2C RNASEH2B RNASEH2A ERCC6
15 sting-associated vasculopathy with onset in infancy 30.4 STING1 SAMHD1 RNASEH2C RNASEH2B RNASEH2A IRF3
16 aicardi-goutieres syndrome 7 11.9
17 aicardi-goutieres syndrome 6 11.9
18 pseudo-torch syndrome 1 11.4
19 encephalopathy 11.4
20 striatonigral degeneration, infantile 11.2
21 aicardi syndrome 11.2
22 congenital intrauterine infection-like syndrome 11.2
23 singleton-merten syndrome 11.2
24 gastric cancer 10.8
25 gastric adenocarcinoma 10.7
26 immunodeficiency 38 with basal ganglia calcification 10.5 RNASEH2C RNASEH2B RNASEH2A
27 visual cortex disease 10.5 RNASEH2C RNASEH2B RNASEH2A
28 visual pathway disease 10.5 RNASEH2C RNASEH2B RNASEH2A
29 prolidase deficiency 10.5 RNASEH2C RNASEH2B RNASEH2A
30 neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities 10.5 RNASEH2C KAT5
31 basal ganglia disease 10.5 SAMHD1 RNASEH2C RNASEH2B RNASEH2A IFIH1 ERCC6
32 xeroderma pigmentosum, complementation group g 10.5 WRN H2AC18 EXO1 ERCC6
33 microphthalmia with limb anomalies 10.5 IRF3 IFIH1 H2AC18 CGAS ADAR
34 rothmund-thomson syndrome, type 2 10.5 WRN EXO1 ERCC6
35 herpangina 10.5 IRF3 IFIH1 H2AC18
36 seckel syndrome 10.5 WRN H2AC18 EXO1 ERCC6 ATRIP
37 coronavirus infectious disease 10.5 IRF3 IFIH1 H2AC18
38 fanconi anemia, complementation group j 10.5 WRN H2AC18 ERCC6
39 lens disease 10.5 WRN H2AC18 ERCC6
40 xeroderma pigmentosum, variant type 10.5 WRN H2AC18 EXO1 ERCC6 ATRIP
41 fanconi anemia, complementation group a 10.5 WRN IRF3 H2AC18 EXO1 ERCC6 ATRIP
42 vasculopathy, retinal, with cerebral leukoencephalopathy and systemic manifestations 10.4 TREX1 STING1 SAMHD1 RNASEH2C RNASEH2B RNASEH2A
43 herpes simplex 10.4 STING1 IRF3 IFIH1 CGAS
44 quadriplegia 10.4
45 hutchinson-gilford progeria syndrome 10.4 WRN H2AC18 ERCC6
46 muscle tissue disease 10.4 IFIH1 H2AC18 ERCC6
47 cerebral palsy 10.4
48 gastritis 10.4
49 nijmegen breakage syndrome 10.4 WRN H2AC18 ERCC6
50 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 10.4

Graphical network of the top 20 diseases related to Aicardi-Goutieres Syndrome:



Diseases related to Aicardi-Goutieres Syndrome

Symptoms & Phenotypes for Aicardi-Goutieres Syndrome

Human phenotypes related to Aicardi-Goutieres Syndrome:

58 31 (show top 50) (show all 76)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
2 arrhinencephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0002139
3 intellectual disability, profound 58 31 hallmark (90%) Very frequent (99-80%) HP:0002187
4 multifocal cerebral white matter abnormalities 58 31 hallmark (90%) Very frequent (99-80%) HP:0007052
5 porencephalic cyst 31 hallmark (90%) HP:0002132
6 cerebral calcification 58 31 frequent (33%) Frequent (79-30%) HP:0002514
7 developmental regression 58 31 frequent (33%) Frequent (79-30%) HP:0002376
8 microcephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000252
9 short stature 58 31 frequent (33%) Frequent (79-30%) HP:0004322
10 dry skin 58 31 frequent (33%) Frequent (79-30%) HP:0000958
11 elevated hepatic transaminase 58 31 frequent (33%) Frequent (79-30%) HP:0002910
12 autoimmunity 58 31 frequent (33%) Frequent (79-30%) HP:0002960
13 irritability 58 31 frequent (33%) Frequent (79-30%) HP:0000737
14 hemiplegia/hemiparesis 58 31 frequent (33%) Frequent (79-30%) HP:0004374
15 ventriculomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0002119
16 dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0001332
17 hypoplasia of the corpus callosum 58 31 frequent (33%) Frequent (79-30%) HP:0002079
18 leukodystrophy 58 31 frequent (33%) Frequent (79-30%) HP:0002415
19 hepatosplenomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0001433
20 difficulty walking 58 31 frequent (33%) Frequent (79-30%) HP:0002355
21 unexplained fevers 58 31 frequent (33%) Frequent (79-30%) HP:0001955
22 increased csf interferon alpha 58 31 frequent (33%) Frequent (79-30%) HP:0009709
23 brain atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0012444
24 increased serum interferon-gamma level 58 31 frequent (33%) Frequent (79-30%) HP:0030356
25 loss of speech 58 31 frequent (33%) Frequent (79-30%) HP:0002371
26 large beaked nose 58 31 frequent (33%) Frequent (79-30%) HP:0003683
27 extrapyramidal muscular rigidity 58 31 frequent (33%) Frequent (79-30%) HP:0007076
28 muscular hypotonia of the trunk 58 31 frequent (33%) Frequent (79-30%) HP:0008936
29 chronic csf lymphocytosis 58 31 frequent (33%) Frequent (79-30%) HP:0009704
30 seizure 31 frequent (33%) HP:0001250
31 eyelid coloboma 31 frequent (33%) HP:0000625
32 chilblains 31 frequent (33%) HP:0009710
33 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
34 abnormal pyramidal sign 58 31 occasional (7.5%) Occasional (29-5%) HP:0007256
35 ptosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000508
36 nystagmus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000639
37 tremor 58 31 occasional (7.5%) Occasional (29-5%) HP:0001337
38 diabetes mellitus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000819
39 hypothyroidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000821
40 arthritis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001369
41 acrocyanosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001063
42 cardiomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0001640
43 spastic tetraplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002510
44 low-set ears 58 31 occasional (7.5%) Occasional (29-5%) HP:0000369
45 multiple joint contractures 58 31 occasional (7.5%) Occasional (29-5%) HP:0002828
46 muscle stiffness 58 31 occasional (7.5%) Occasional (29-5%) HP:0003552
47 micropenis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000054
48 hoarse voice 58 31 occasional (7.5%) Occasional (29-5%) HP:0001609
49 headache 58 31 occasional (7.5%) Occasional (29-5%) HP:0002315
50 plagiocephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0001357

UMLS symptoms related to Aicardi-Goutieres Syndrome:


seizures, petechiae of skin

GenomeRNAi Phenotypes related to Aicardi-Goutieres Syndrome according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-1 9.4 ERCC6
2 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 9.4 ERCC6 EXO1 RNASEH2A RNASEH2C
3 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-3 9.4 ERCC6 EXO1 KAT5 RNASEH2A RNASEH2B RNASEH2C

MGI Mouse Phenotypes related to Aicardi-Goutieres Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.03 ADAR ATRIP ERCC6 EXO1 IFIH1 IRF3
2 hematopoietic system MP:0005397 9.9 ADAR CGAS ERCC6 EXO1 IFIH1 IRF3
3 immune system MP:0005387 9.77 ADAR CGAS ERCC6 EXO1 IFIH1 IRF3
4 mortality/aging MP:0010768 9.47 ADAR ATRIP CGAS ERCC6 EXO1 IFIH1

Drugs & Therapeutics for Aicardi-Goutieres Syndrome

Drugs for Aicardi-Goutieres Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 17)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Adenosine Approved, Investigational Phase 1, Phase 2 58-61-7 60961
2
Emtricitabine Approved, Investigational Phase 1, Phase 2 143491-57-0 60877
3
Abacavir Approved, Investigational Phase 2 136470-78-5 65140 441300
4
Lamivudine Approved, Investigational Phase 2 134678-17-4 60825
5
Zidovudine Approved Phase 2 30516-87-1 35370
6
Tenofovir Experimental, Investigational Phase 1, Phase 2 147127-20-6 464205
7 Janus Kinase Inhibitors Phase 2
8 Anti-HIV Agents Phase 1, Phase 2
9 Anti-Infective Agents Phase 1, Phase 2
10 Reverse Transcriptase Inhibitors Phase 1, Phase 2
11 Antiviral Agents Phase 1, Phase 2
12 interferons Phase 1, Phase 2
13 Anti-Retroviral Agents Phase 1, Phase 2
14 Pharmaceutical Solutions Phase 2
15 Antimetabolites Phase 2
16 Interferon Type I Phase 2
17 Dideoxynucleosides Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Pilot Clinical Trial of Reverse Transcriptase Inhibitors in Children With Aicardi-Goutières Syndrome (AGS) Completed NCT02363452 Phase 2 Reverse transcriptase inhibitors: Zidovudine, Lamivudine, Abacavir
2 Janus Kinase Inhibitor (Baricitinib) for Aicardi Goutières Syndrome Active, not recruiting NCT03921554 Phase 2 Baricitinib
3 Reverse Transcriptase Inhibitors in Aicardi Goutières Syndrome Not yet recruiting NCT03304717 Phase 1, Phase 2 Tenofovir (TDF) and Emtricitabine (FTC)
4 Inhibition of Reverse Transcription in Type I Interferon Mediated Neuropathology Not yet recruiting NCT04731103 Phase 2 Abacavir (ABC);Lamivudine (3TC);Abacavir (ABC)+Lamivudine (3TC)+Zidovudine (AZT)

Search NIH Clinical Center for Aicardi-Goutieres Syndrome

Genetic Tests for Aicardi-Goutieres Syndrome

Genetic tests related to Aicardi-Goutieres Syndrome:

# Genetic test Affiliating Genes
1 Aicardi Goutieres Syndrome 29

Anatomical Context for Aicardi-Goutieres Syndrome

MalaCards organs/tissues related to Aicardi-Goutieres Syndrome:

40
Brain, Liver, Spleen, Spinal Cord, Eye, Bone Marrow, Skin

Publications for Aicardi-Goutieres Syndrome

Articles related to Aicardi-Goutieres Syndrome:

(show top 50) (show all 119)
# Title Authors PMID Year
1
Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. 61 25 6
25604658 2015
2
Clinical and molecular phenotype of Aicardi-Goutieres syndrome. 6 25 61
17846997 2007
3
Genetic syndromes mimic congenital infections. 25 6 61
15870678 2005
4
Mutations in ADAR1, IFIH1, and RNASEH2B presenting as spastic paraplegia. 25 6
25243380 2014
5
Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling. 6 25
24686847 2014
6
A type I interferon signature identifies bilateral striatal necrosis due to mutations in ADAR1. 25 6
24262145 2014
7
Autosomal dominant inheritance of a heterozygous mutation in SAMHD1 causing familial chilblain lupus. 6 25
21204240 2011
8
Familial Aicardi-Goutières syndrome due to SAMHD1 mutations is associated with chronic arthropathy and contractures. 6 25
20358604 2010
9
Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response. 25 6
19525956 2009
10
Dyschromatosis symmetrica hereditaria associated with neurological disorders. 25 6
19017046 2008
11
Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus. 25 6
17660818 2007
12
Dystonia, mental deterioration, and dyschromatosis symmetrica hereditaria in a family with ADAR1 mutation. 25 6
16817193 2006
13
Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus. 25 6
16845398 2006
14
Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection. 25 6
16845400 2006
15
Functional consequences of the RNase H2A subunit mutations that cause Aicardi-Goutieres syndrome. 6 61
21454563 2011
16
Aicardi goutières syndrome is associated with pulmonary hypertension. 6
30219631 2018
17
Aicardi-Goutières syndrome is caused by IFIH1 mutations. 6
24995871 2014
18
Heterozygous TREX1 p.Asp18Asn mutation can cause variable neurological symptoms in a family with Aicardi-Goutieres syndrome/familial chilblain lupus. 25 61
22829693 2013
19
Striking intrafamilial phenotypic variability in Aicardi-Goutières syndrome associated with the recurrent Asian founder mutation in RNASEH2C. 6
23322642 2013
20
Cerebral vasculopathy is a common feature in Aicardi-Goutieres syndrome associated with SAMHD1 mutations. 61 25
21633013 2011
21
A large homozygous deletion in the SAMHD1 gene causes atypical Aicardi-Goutiéres syndrome associated with mtDNA deletions. 6
21102625 2011
22
Aicardi-Goutieres syndrome: neuroradiologic findings and follow-up. 61 25
19628626 2009
23
Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity. 61 25
19808788 2009
24
Trex1 prevents cell-intrinsic initiation of autoimmunity. 25 61
18724932 2008
25
Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi-Goutieres syndrome. 61 25
17357087 2007
26
Human disease phenotypes associated with mutations in TREX1. 25
25731743 2015
27
Leukoencephalopathy with calcifications and cysts: a purely neurological disorder distinct from coats plus. 25
24407470 2014
28
Bilateral striatal necrosis in two subjects with Aicardi-Goutières syndrome due to mutations in ADAR1 (AGS6). 25
24376015 2014
29
A nationwide survey of Aicardi-Goutières syndrome patients identifies a strong association between dominant TREX1 mutations and chilblain lesions: Japanese cohort study. 25
24300241 2014
30
Therapies in Aicardi-Goutières syndrome. 25
23607857 2014
31
Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study. 25
24183309 2013
32
Synonymous mutations in RNASEH2A create cryptic splice sites impairing RNase H2 enzyme function in Aicardi-Goutières syndrome. 25
23592335 2013
33
Recognizable phenotypes associated with intracranial calcification. 25
23121296 2013
34
Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature. 25
23001123 2012
35
Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus. 25
22267198 2012
36
HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase. 25
22056990 2011
37
Homozygous mutation in SAMHD1 gene causes cerebral vasculopathy and early onset stroke. 25
21402907 2011
38
Cerebral arterial stenoses and stroke: novel features of Aicardi-Goutières syndrome caused by the Arg164X mutation in SAMHD1 are associated with altered cytokine expression. 25
20842748 2010
39
A de novo p.Asp18Asn mutation in TREX1 in a patient with Aicardi-Goutières syndrome. 25
20799324 2010
40
Recessive mutations in the gene encoding the tight junction protein occludin cause band-like calcification with simplified gyration and polymicrogyria. 25
20727516 2010
41
Intracerebral large artery disease in Aicardi-Goutières syndrome implicates SAMHD1 in vascular homeostasis. 25
20653736 2010
42
Expanding the phenotypic spectrum of lupus erythematosus in Aicardi-Goutières syndrome. 25
20131292 2010
43
Band-like intracranial calcification with simplified gyration and polymicrogyria: a distinct "pseudo-TORCH" phenotype. 25
19012351 2008
44
Microcephaly, malformation of brain development and intracranial calcification in sibs: pseudo-TORCH or a new syndrome. 25
18925673 2008
45
Trex1 exonuclease degrades ssDNA to prevent chronic checkpoint activation and autoimmune disease. 25
18045533 2007
46
C-terminal truncations in human 3'-5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. 25
17660820 2007
47
A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus. 25
17440703 2007
48
Cerebroretinal microangiopathy with calcifications and cysts. 25
16943371 2006
49
Elevated interferon-alpha in fetal blood in the prenatal diagnosis of Aicardi-Goutières syndrome. 25
16354995 2006
50
Severe fetal brain dysgenesis with focal calcification. 25
15906425 2005

Variations for Aicardi-Goutieres Syndrome

ClinVar genetic disease variations for Aicardi-Goutieres Syndrome:

6 (show top 50) (show all 990)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SAMHD1 NC_000020.11:g.(36898545_36904156)_(36951644_?)del Deletion Pathogenic 126402 20:35526948-35580047 20:36898545-36951644
2 SAMHD1 NM_015474.3:c.(Exons12-16del) Deletion Pathogenic 126403
3 SAMHD1 NM_015474.3(SAMHD1):c.1411-2A>G SNV Pathogenic 126407 rs515726141 20:35532654-35532654 20:36904251-36904251
4 SAMHD1 NM_015474.3(SAMHD1):c.1503+1G>T SNV Pathogenic 126408 rs515726142 20:35532559-35532559 20:36904156-36904156
5 SAMHD1 NM_015474.3(SAMHD1):c.1609-1G>C SNV Pathogenic 126409 rs515726143 20:35526363-35526363 20:36897960-36897960
6 RNASEH2C NM_032193.3(RNASEH2C):c.428A>T (p.Lys143Ile) SNV Pathogenic 1261 rs75146158 11:65487556-65487556 11:65720085-65720085
7 SAMHD1 NC_000020.11:g.(?_36946728)_(36951653_?)del Deletion Pathogenic 830998 20:35575131-35580056
8 SAMHD1 NC_000020.11:g.(?_36951436)_(36951643_?)del Deletion Pathogenic 833165 20:35579839-35580046
9 SAMHD1 NM_015474.4(SAMHD1):c.939G>A (p.Trp313Ter) SNV Pathogenic 840434 20:35545366-35545366 20:36916963-36916963
10 SAMHD1 NM_015474.4(SAMHD1):c.1368T>G (p.Tyr456Ter) SNV Pathogenic 847483 20:35533809-35533809 20:36905406-36905406
11 SAMHD1 NM_015474.4(SAMHD1):c.66del (p.Ser23fs) Deletion Pathogenic 858736 20:35579981-35579981 20:36951578-36951578
12 SAMHD1 NM_015474.4(SAMHD1):c.580C>T (p.Arg194Ter) SNV Pathogenic 861422 20:35559208-35559208 20:36930805-36930805
13 SAMHD1 NM_015474.3(SAMHD1):c.700G>T (p.Glu234Ter) SNV Pathogenic 639210 rs1219206348 20:35547919-35547919 20:36919516-36919516
14 SAMHD1 NM_015474.3(SAMHD1):c.400C>T (p.Arg134Ter) SNV Pathogenic 645045 rs752442185 20:35563541-35563541 20:36935138-36935138
15 RNASEH2B NM_001142279.2(RNASEH2B):c.510+1G>A SNV Pathogenic 650490 rs77301371 13:51517531-51517531 13:50943395-50943395
16 SAMHD1 NM_015474.3(SAMHD1):c.658C>T (p.Arg220Ter) SNV Pathogenic 659536 rs1335417539 20:35555623-35555623 20:36927220-36927220
17 SAMHD1 NM_015474.4(SAMHD1):c.1476del (p.Lys492fs) Deletion Pathogenic 659887 rs768409471 20:35532587-35532587 20:36904184-36904184
18 RNASEH2B NM_024570.4(RNASEH2B):c.136+1del Deletion Pathogenic 566198 rs75186889 13:51501614-51501614 13:50927478-50927478
19 SAMHD1 NM_015474.4(SAMHD1):c.1022_1028del (p.Val340_Cys341insTer) Deletion Pathogenic 943467 20:35545159-35545165 20:36916756-36916762
20 SAMHD1 NM_015474.4(SAMHD1):c.1105_1106del (p.Leu369fs) Deletion Pathogenic 946951 20:35540912-35540913 20:36912509-36912510
21 RNASEH2A NM_006397.2(RNASEH2A):c.704G>A (p.Arg235Gln) SNV Pathogenic 66066 rs75718910 19:12923963-12923963 19:12813149-12813149
22 RNASEH2A NM_006397.2(RNASEH2A):c.207dup (p.Thr70fs) Duplication Pathogenic 126396 rs77672568 19:12918026-12918027 19:12807212-12807213
23 RNASEH2A NM_006397.2(RNASEH2A):c.690C>A (p.Phe230Leu) SNV Pathogenic 126398 rs79767407 19:12923949-12923949 19:12813135-12813135
24 RNASEH2A NM_006397.2(RNASEH2A):c.719C>T (p.Thr240Met) SNV Pathogenic 126400 rs79843600 19:12923978-12923978 19:12813164-12813164
25 RNASEH2A NM_006397.2(RNASEH2A):c.872G>A (p.Arg291His) SNV Pathogenic 126401 rs75037667 19:12924252-12924252 19:12813438-12813438
26 SAMHD1 NM_015474.3(SAMHD1):c.649_650insG (p.Phe217fs) Insertion Pathogenic 126413 rs515726146 20:35555631-35555632 20:36927228-36927229
27 SAMHD1 NM_015474.3(SAMHD1):c.1408del (p.Arg470fs) Deletion Pathogenic 581566 rs1568762986 20:35533769-35533769 20:36905366-36905366
28 SAMHD1 NM_015474.3(SAMHD1):c.494_495dup (p.Glu166fs) Duplication Pathogenic 639026 rs1601144527 20:35563445-35563446 20:36935042-36935043
29 RNASEH2B NM_024570.4(RNASEH2B):c.491dup (p.Leu164fs) Duplication Pathogenic 870598 13:51517509-51517510 13:50943373-50943374
30 SAMHD1 NM_015474.4(SAMHD1):c.152_155dup (p.Phe53fs) Duplication Pathogenic 969961 20:35579891-35579892 20:36951488-36951489
31 RNASEH2A NM_006397.2(RNASEH2A):c.714_715GC[3] (p.Thr240fs) Microsatellite Pathogenic 126399 rs78705193 19:12923972-12923973 19:12813158-12813159
32 RNASEH2B NM_001142279.2(RNASEH2B):c.667G>T (p.Glu223Ter) SNV Pathogenic 540251 rs1555257383 13:51522173-51522173 13:50948037-50948037
33 RNASEH2B NM_001142279.2(RNASEH2B):c.121del (p.Val41fs) Deletion Pathogenic 567225 rs1452451283 13:51501598-51501598 13:50927462-50927462
34 RNASEH2B NM_001142279.2(RNASEH2B):c.719C>G (p.Ser240Ter) SNV Pathogenic 582587 rs372632599 13:51523619-51523619 13:50949483-50949483
35 RNASEH2B NM_001142279.2(RNASEH2B):c.488C>T (p.Thr163Ile) SNV Pathogenic 650668 rs79310911 13:51517508-51517508 13:50943372-50943372
36 SAMHD1 NC_000020.11:g.(?_36951426)_(36951653_?)del Deletion Pathogenic 653534 20:35579829-35580056 20:36951426-36951653
37 SAMHD1 NC_000020.11:g.(?_36951416)_(36951663_?)del Deletion Pathogenic 658990 20:35579819-35580066 20:36951416-36951663
38 SAMHD1 NM_015474.3(SAMHD1):c.-6085_209-1941del Deletion Pathogenic 30603 20:35577148-35586131 20:36948745-36957728
39 ATRIP NM_033629.6(TREX1):c.602T>A (p.Val201Asp) SNV Pathogenic 4182 rs78408272 3:48508656-48508656 3:48467257-48467257
40 ATRIP NM_033629.6(TREX1):c.500del (p.Ser167fs) Deletion Pathogenic 126389 rs76642637 3:48508554-48508554 3:48467155-48467155
41 ATRIP NM_033629.6(TREX1):c.58dup (p.Glu20fs) Duplication Pathogenic 126390 rs78300695 3:48508110-48508111 3:48466711-48466712
42 ATRIP NM_033629.6(TREX1):c.598G>A (p.Asp200Asn) SNV Pathogenic 4184 rs78846775 3:48508652-48508652 3:48467253-48467253
43 ATRIP NM_033629.6(TREX1):c.609_662dup (p.Leu204_Ala221dup) Duplication Pathogenic 126391 rs78379807 3:48508660-48508661 3:48467261-48467262
44 ATRIP NM_033629.6(TREX1):c.625_628dup (p.Trp210fs) Duplication Pathogenic 126392 rs78948846 3:48508676-48508677 3:48467277-48467278
45 ADAR NM_001111.5(ADAR):c.1630C>T (p.Arg544Ter) SNV Pathogenic 126560 rs768943773 1:154571033-154571033 1:154598557-154598557
46 IFIH1 NM_022168.4(IFIH1):c.2159G>A (p.Arg720Gln) SNV Pathogenic 137621 rs587777445 2:163133342-163133342 2:162276832-162276832
47 IFIH1 NM_022168.4(IFIH1):c.2336G>A (p.Arg779His) SNV Pathogenic 137622 rs587777446 2:163130423-163130423 2:162273913-162273913
48 IFIH1 NM_022168.4(IFIH1):c.1009A>G (p.Arg337Gly) SNV Pathogenic 137623 rs587777447 2:163144731-163144731 2:162288221-162288221
49 IFIH1 NM_022168.4(IFIH1):c.2335C>T (p.Arg779Cys) SNV Pathogenic 137624 rs587777448 2:163130424-163130424 2:162273914-162273914
50 IFIH1 NM_022168.4(IFIH1):c.1483G>A (p.Gly495Arg) SNV Pathogenic 137625 rs672601336 2:163137879-163137879 2:162281369-162281369

Expression for Aicardi-Goutieres Syndrome

Search GEO for disease gene expression data for Aicardi-Goutieres Syndrome.

Pathways for Aicardi-Goutieres Syndrome

Pathways related to Aicardi-Goutieres Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 Cytosolic DNA-sensing pathway hsa04623
2 DNA replication hsa03030
3 RIG-I-like receptor signaling pathway hsa04622

GO Terms for Aicardi-Goutieres Syndrome

Cellular components related to Aicardi-Goutieres Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleoplasm GO:0005654 9.9 WRN STING1 SAMHD1 RNASEH2B RNASEH2A KAT5
2 nucleus GO:0005634 9.86 WRN TREX1 TLDC2 SAMHD1 RNASEH2C RNASEH2B
3 ribonuclease H2 complex GO:0032299 8.8 RNASEH2C RNASEH2B RNASEH2A

Biological processes related to Aicardi-Goutieres Syndrome according to GeneCards Suite gene sharing:

(show all 31)
# Name GO ID Score Top Affiliating Genes
1 immune system process GO:0002376 10.05 STING1 SAMHD1 IRF3 IFIH1 EXO1 CGAS
2 viral process GO:0016032 10.04 STING1 SAMHD1 KAT5 IRF3 IFIH1 CGAS
3 innate immune response GO:0045087 10.02 TREX1 STING1 SAMHD1 IRF3 IFIH1 CGAS
4 cellular response to DNA damage stimulus GO:0006974 9.92 WRN TREX1 SAMHD1 IRF3 EXO1 ERCC6
5 DNA repair GO:0006281 9.91 WRN TREX1 SAMHD1 EXO1 ERCC6 CGAS
6 regulation of signal transduction by p53 class mediator GO:1901796 9.86 WRN KAT5 EXO1 ATRIP
7 response to oxidative stress GO:0006979 9.82 WRN TLDC2 ERCC6
8 DNA recombination GO:0006310 9.81 WRN TREX1 EXO1
9 regulation of inflammatory response GO:0050727 9.8 TREX1 STING1 IRF3
10 nucleic acid phosphodiester bond hydrolysis GO:0090305 9.8 WRN TREX1 RNASEH2A EXO1 ATRIP
11 DNA duplex unwinding GO:0032508 9.78 WRN TREX1 ERCC6
12 RNA phosphodiester bond hydrolysis, endonucleolytic GO:0090502 9.77 RNASEH2B RNASEH2A EXO1
13 positive regulation of type I interferon production GO:0032481 9.76 STING1 IRF3 CGAS
14 type I interferon signaling pathway GO:0060337 9.73 TREX1 SAMHD1 IRF3 ADAR
15 positive regulation of defense response to virus by host GO:0002230 9.71 STING1 ERCC6 CGAS
16 mismatch repair GO:0006298 9.7 TREX1 RNASEH2A EXO1
17 RNA catabolic process GO:0006401 9.67 RNASEH2C RNASEH2B RNASEH2A
18 cellular response to interferon-beta GO:0035458 9.65 TREX1 STING1
19 regulation of innate immune response GO:0045088 9.64 TREX1 SAMHD1
20 determination of adult lifespan GO:0008340 9.64 TREX1 CGAS
21 somatic hypermutation of immunoglobulin genes GO:0016446 9.63 SAMHD1 EXO1
22 negative regulation of type I interferon-mediated signaling pathway GO:0060339 9.63 TREX1 SAMHD1 ADAR
23 t-circle formation GO:0090656 9.62 WRN EXO1
24 regulation of T cell activation GO:0050863 9.61 TREX1 CGAS
25 regulation of immunoglobulin production GO:0002637 9.6 TREX1 CGAS
26 regulation of cellular metabolic process GO:0031323 9.58 TREX1 STING1
27 cellular response to exogenous dsRNA GO:0071360 9.56 STING1 IRF3 IFIH1 CGAS
28 MDA-5 signaling pathway GO:0039530 9.55 IRF3 IFIH1
29 defense response to virus GO:0051607 9.5 TREX1 STING1 SAMHD1 IRF3 IFIH1 CGAS
30 regulation of type I interferon production GO:0032479 9.46 TREX1 STING1 IRF3 CGAS
31 DNA replication GO:0006260 9.17 WRN TREX1 SAMHD1 RNASEH2A KAT5 EXO1

Molecular functions related to Aicardi-Goutieres Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hydrolase activity GO:0016787 9.97 WRN TREX1 SAMHD1 RNASEH2A IFIH1 EXO1
2 DNA binding GO:0003677 9.97 WRN TREX1 IRF3 IFIH1 H2AC18 EXO1
3 nuclease activity GO:0004518 9.46 WRN TREX1 RNASEH2A EXO1
4 3'-5' exonuclease activity GO:0008408 9.4 WRN TREX1
5 MutLalpha complex binding GO:0032405 9.26 WRN TREX1
6 RNA-DNA hybrid ribonuclease activity GO:0004523 9.13 RNASEH2B RNASEH2A EXO1
7 exonuclease activity GO:0004527 8.92 WRN TREX1 EXO1 ATRIP

Sources for Aicardi-Goutieres Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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