AGS3
MCID: ACR088
MIFTS: 36

Aicardi-Goutieres Syndrome 3 (AGS3)

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

Aliases & Classifications for Aicardi-Goutieres Syndrome 3

MalaCards integrated aliases for Aicardi-Goutieres Syndrome 3:

Name: Aicardi-Goutieres Syndrome 3 58 76 13 74
Ags3 58 54 76
Aicardi Goutieres Syndrome 3 30 6
Pseudo-Torch Syndrome 76 74
Rnaseh2c -Related Aicardi-Goutieres Syndrome 54
Aicardi-Goutieres Syndrome, Type 3 41
Aicardi-Goutieres Syndrome Type 3 54
Aicardi-Goutieres Syndrome 1 74
Cree Encephalitis 76

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset in early infancy
one patient with normal psychomotor development has been reported


HPO:

33
aicardi-goutieres syndrome 3:
Mortality/Aging death in childhood
Onset and clinical course progressive
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Aicardi-Goutieres Syndrome 3

NIH Rare Diseases : 54 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.

MalaCards based summary : Aicardi-Goutieres Syndrome 3, also known as ags3, is related to aicardi-goutieres syndrome and pseudo-torch syndrome 1, and has symptoms including seizures, muscle spasticity and petechiae of skin. An important gene associated with Aicardi-Goutieres Syndrome 3 is RNASEH2C (Ribonuclease H2 Subunit C). Affiliated tissues include brain, skin and spinal cord, and related phenotypes are nystagmus and spasticity

OMIM : 58 Aicardi-Goutieres syndrome is an autosomal recessive disorder characterized by onset of encephalopathy in the first year of life following normal early development. Affected infants typically show extreme irritability, intermittent unexplained fever, chilblains, progressive microcephaly, spasticity, dystonia, and profound psychomotor retardation. Laboratory studies show lymphocytosis and raised titers of alpha-interferon in the cerebrospinal fluid. Brain imaging may show white matter abnormalities, intracerebral calcifications, and cerebral atrophy. Many patients die in childhood (summary by Vogt et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of Aicardi-Goutieres syndrome, see AGS1 (225750). (610329)

UniProtKB/Swiss-Prot : 76 Aicardi-Goutieres syndrome 3: A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood.

Related Diseases for Aicardi-Goutieres Syndrome 3

Graphical network of the top 20 diseases related to Aicardi-Goutieres Syndrome 3:



Diseases related to Aicardi-Goutieres Syndrome 3

Symptoms & Phenotypes for Aicardi-Goutieres Syndrome 3

Human phenotypes related to Aicardi-Goutieres Syndrome 3:

33 (show all 15)
# Description HPO Frequency HPO Source Accession
1 nystagmus 33 HP:0000639
2 spasticity 33 HP:0001257
3 hyperreflexia 33 HP:0001347
4 cerebral calcification 33 HP:0002514
5 severe global developmental delay 33 HP:0011344
6 dystonia 33 HP:0001332
7 thrombocytopenia 33 HP:0001873
8 generalized hypotonia 33 HP:0001290
9 encephalopathy 33 HP:0001298
10 hypoplasia of the corpus callosum 33 HP:0002079
11 hepatosplenomegaly 33 HP:0001433
12 progressive microcephaly 33 HP:0000253
13 delayed myelination 33 HP:0012448
14 csf lymphocytic pleiocytosis 33 HP:0200149
15 elevated hepatic transaminase 33 HP:0002910

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
nystagmus
roving eye movements
visual inattention

Head And Neck Head:
microcephaly

Skin Nails Hair Skin:
chilblains

Neurologic Central Nervous System:
hyperreflexia
encephalopathy
delayed myelination
intracranial calcifications
thin corpus callosum
more
Muscle Soft Tissue:
hypotonia

Laboratory Abnormalities:
increased csf alpha-interferon
csf lymphocytosis
increased serum alpha-interferon

Clinical features from OMIM:

610329

UMLS symptoms related to Aicardi-Goutieres Syndrome 3:


seizures, muscle spasticity, petechiae of skin

GenomeRNAi Phenotypes related to Aicardi-Goutieres Syndrome 3 according to GeneCards Suite gene sharing:

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased homologous recombination repair frequency GR00236-A-1 9.56 KAT5 RNASEH2C
2 Decreased homologous recombination repair frequency GR00236-A-2 9.56 KAT5 RNASEH2C
3 Increased viability with MLN4924 (a NAE inhibitor) GR00250-A-3 8.62 KAT5 RNASEH2C

Drugs & Therapeutics for Aicardi-Goutieres Syndrome 3

Search Clinical Trials , NIH Clinical Center for Aicardi-Goutieres Syndrome 3

Genetic Tests for Aicardi-Goutieres Syndrome 3

Genetic tests related to Aicardi-Goutieres Syndrome 3:

# Genetic test Affiliating Genes
1 Aicardi Goutieres Syndrome 3 30 RNASEH2C

Anatomical Context for Aicardi-Goutieres Syndrome 3

MalaCards organs/tissues related to Aicardi-Goutieres Syndrome 3:

42
Brain, Skin, Spinal Cord, Eye, Cortex

Publications for Aicardi-Goutieres Syndrome 3

Articles related to Aicardi-Goutieres Syndrome 3:

(show all 17)
# Title Authors Year
1
Role of G-proteins and phosphorylation in the distribution of AGS3 to cell puncta. ( 30404823 )
2018
2
Extensive intracranial calcification of pseudo-TORCH syndrome with features of Dandy-Walker malformation. ( 28761539 )
2017
3
Loss of the canonical spindle orientation function in the Pins/LGN homolog AGS3. ( 28684399 )
2017
4
Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome. ( 27325888 )
2016
5
AGS3 is involved in TNF-α medicated osteogenic differentiation of human dental pulp stem cells. ( 26143356 )
2015
6
Defective chemokine signal integration in leukocytes lacking activator of G protein signaling 3 (AGS3). ( 24573680 )
2014
7
Anaesthetic Management of a Patient with Pseudo-TORCH Syndrome. ( 25207129 )
2013
8
Increased expression of AGS3 in rat brain cortex after traumatic brain injury. ( 23404409 )
2013
9
Normal autophagic activity in macrophages from mice lacking Gαi3, AGS3, or RGS19. ( 24312373 )
2013
10
Up-regulation of AGS3 during morphine withdrawal promotes cAMP superactivation via adenylyl cyclase 5 and 7 in rat nucleus accumbens/striatal neurons. ( 19549762 )
2009
11
Ric-8A catalyzes guanine nucleotide exchange on G alphai1 bound to the GPR/GoLoco exchange inhibitor AGS3. ( 18541531 )
2008
12
G protein betagamma subunits and AGS3 control spindle orientation and asymmetric cell fate of cerebral cortical progenitors. ( 16009138 )
2005
13
AGS3 and signal integration by Galpha(s)- and Galpha(i)-coupled receptors: AGS3 blocks the sensitization of adenylyl cyclase following prolonged stimulation of a Galpha(i)-coupled receptor by influencing processing of Galpha(i). ( 14726514 )
2004
14
Two brothers with findings resembling congenital intrauterine infection-like syndrome (pseudo-TORCH syndrome). ( 12833411 )
2003
15
Asymmetrically distributed C. elegans homologs of AGS3/PINS control spindle position in the early embryo. ( 12814548 )
2003
16
Influence of cytosolic AGS3 on receptor--G protein coupling. ( 12834360 )
2003
17
Pseudo-TORCH syndrome or Baraitser-Reardon syndrome: diagnostic criteria. ( 11226724 )
2001

Variations for Aicardi-Goutieres Syndrome 3

UniProtKB/Swiss-Prot genetic disease variations for Aicardi-Goutieres Syndrome 3:

76
# Symbol AA change Variation ID SNP ID
1 RNASEH2C p.Arg69Trp VAR_027287 rs78635798
2 RNASEH2C p.Lys143Ile VAR_027288 rs75146158
3 RNASEH2C p.Arg13His VAR_070618 rs75328625
4 RNASEH2C p.Asp39Tyr VAR_070619 rs773527127
5 RNASEH2C p.Pro76Leu VAR_070620 rs76091978
6 RNASEH2C p.Pro138Leu VAR_070621
7 RNASEH2C p.Pro151Ser VAR_070622 rs78464826

ClinVar genetic disease variations for Aicardi-Goutieres Syndrome 3:

6 (show all 28)
# Gene Variation Type Significance SNP ID Assembly Location
1 RNASEH2C NM_032193.3(RNASEH2C): c.434G> C (p.Arg145Pro) single nucleotide variant Uncertain significance rs774773395 GRCh38 Chromosome 11, 65720079: 65720079
2 RNASEH2C NM_032193.3(RNASEH2C): c.434G> C (p.Arg145Pro) single nucleotide variant Uncertain significance rs774773395 GRCh37 Chromosome 11, 65487550: 65487550
3 RNASEH2C NM_032193.3(RNASEH2C): c.178dup (p.Glu60Glyfs) duplication Likely pathogenic rs772940104 GRCh38 Chromosome 11, 65720412: 65720412
4 RNASEH2C NM_032193.3(RNASEH2C): c.178dup (p.Glu60Glyfs) duplication Likely pathogenic rs772940104 GRCh37 Chromosome 11, 65487883: 65487883
5 RNASEH2C NM_032193.3(RNASEH2C): c.205C> T (p.Arg69Trp) single nucleotide variant Likely pathogenic rs78635798 GRCh37 Chromosome 11, 65487856: 65487856
6 RNASEH2C NM_032193.3(RNASEH2C): c.205C> T (p.Arg69Trp) single nucleotide variant Likely pathogenic rs78635798 GRCh38 Chromosome 11, 65720385: 65720385
7 RNASEH2C NM_032193.3(RNASEH2C): c.428A> T (p.Lys143Ile) single nucleotide variant Pathogenic rs75146158 GRCh37 Chromosome 11, 65487556: 65487556
8 RNASEH2C NM_032193.3(RNASEH2C): c.428A> T (p.Lys143Ile) single nucleotide variant Pathogenic rs75146158 GRCh38 Chromosome 11, 65720085: 65720085
9 RNASEH2C NM_032193.3(RNASEH2C): c.-10A> G single nucleotide variant Benign/Likely benign rs77371161 GRCh37 Chromosome 11, 65488239: 65488239
10 RNASEH2C NM_032193.3(RNASEH2C): c.-10A> G single nucleotide variant Benign/Likely benign rs77371161 GRCh38 Chromosome 11, 65720768: 65720768
11 RNASEH2C NM_032193.3(RNASEH2C): c.468+13G> A single nucleotide variant Conflicting interpretations of pathogenicity rs182000627 GRCh37 Chromosome 11, 65487503: 65487503
12 RNASEH2C NM_032193.3(RNASEH2C): c.468+13G> A single nucleotide variant Conflicting interpretations of pathogenicity rs182000627 GRCh38 Chromosome 11, 65720032: 65720032
13 RNASEH2C NM_032193.3(RNASEH2C): c.417C> G (p.Gly139=) single nucleotide variant Conflicting interpretations of pathogenicity rs147021687 GRCh37 Chromosome 11, 65487567: 65487567
14 RNASEH2C NM_032193.3(RNASEH2C): c.417C> G (p.Gly139=) single nucleotide variant Conflicting interpretations of pathogenicity rs147021687 GRCh38 Chromosome 11, 65720096: 65720096
15 RNASEH2C NM_032193.3(RNASEH2C): c.268_270delAAG (p.Lys90del) deletion Benign/Likely benign rs141875736 GRCh37 Chromosome 11, 65487791: 65487793
16 RNASEH2C NM_032193.3(RNASEH2C): c.268_270delAAG (p.Lys90del) deletion Benign/Likely benign rs141875736 GRCh38 Chromosome 11, 65720320: 65720322
17 RNASEH2C NM_032193.3(RNASEH2C): c.61T> C (p.Leu21=) single nucleotide variant Conflicting interpretations of pathogenicity rs376140250 GRCh37 Chromosome 11, 65488169: 65488169
18 RNASEH2C NM_032193.3(RNASEH2C): c.61T> C (p.Leu21=) single nucleotide variant Conflicting interpretations of pathogenicity rs376140250 GRCh38 Chromosome 11, 65720698: 65720698
19 RNASEH2C NM_032193.3(RNASEH2C): c.468G> T (p.Ala156=) single nucleotide variant Conflicting interpretations of pathogenicity rs61736590 GRCh37 Chromosome 11, 65487516: 65487516
20 RNASEH2C NM_032193.3(RNASEH2C): c.468G> T (p.Ala156=) single nucleotide variant Conflicting interpretations of pathogenicity rs61736590 GRCh38 Chromosome 11, 65720045: 65720045
21 RNASEH2C NM_032193.3(RNASEH2C): c.115G> T (p.Asp39Tyr) single nucleotide variant Uncertain significance rs773527127 GRCh37 Chromosome 11, 65488115: 65488115
22 RNASEH2C NM_032193.3(RNASEH2C): c.115G> T (p.Asp39Tyr) single nucleotide variant Uncertain significance rs773527127 GRCh38 Chromosome 11, 65720644: 65720644
23 RNASEH2C NM_032193.3(RNASEH2C): c.268_269delAAinsGT (p.Lys90Val) indel Uncertain significance GRCh38 Chromosome 11, 65720321: 65720322
24 RNASEH2C NM_032193.3(RNASEH2C): c.268_269delAAinsGT (p.Lys90Val) indel Uncertain significance GRCh37 Chromosome 11, 65487792: 65487793
25 RNASEH2C NM_032193.3(RNASEH2C): c.260A> G (p.Glu87Gly) single nucleotide variant Uncertain significance GRCh38 Chromosome 11, 65720330: 65720330
26 RNASEH2C NM_032193.3(RNASEH2C): c.260A> G (p.Glu87Gly) single nucleotide variant Uncertain significance GRCh37 Chromosome 11, 65487801: 65487801
27 RNASEH2C NM_032193.3(RNASEH2C): c.56C> G (p.Ala19Gly) single nucleotide variant Uncertain significance GRCh37 Chromosome 11, 65488174: 65488174
28 RNASEH2C NM_032193.3(RNASEH2C): c.56C> G (p.Ala19Gly) single nucleotide variant Uncertain significance GRCh38 Chromosome 11, 65720703: 65720703

Expression for Aicardi-Goutieres Syndrome 3

Search GEO for disease gene expression data for Aicardi-Goutieres Syndrome 3.

Pathways for Aicardi-Goutieres Syndrome 3

GO Terms for Aicardi-Goutieres Syndrome 3

Sources for Aicardi-Goutieres Syndrome 3

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