Aicardi-Goutieres Syndrome 3 (AGS3)

External Ids:

OMIM 57 610329 MedGen 42 C1835916 MeSH 44 D009421 D020274

SNOMED-CT via HPO 69 258211005 15805002 563001 221360009 397790002 81308009 86854008 36760000 302215000 415116008 204043002 17944005 166603001 166643006 75183008 252157006 255314001 62211000119103 135810007 167719009 more UMLS 73 C1835916 C0796126 C3489725

NIH Rare Diseases : ⁵³ 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 : ⁵⁷ 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 : ⁷⁵ 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.

Clinical features from OMIM:

610329

#	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

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

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