Aicardi-Goutieres Syndrome 5

Last update 01 Nov 2024

Basic Info

Synonyms

AGS5, AICARDI-GOUTIERES SYNDROME 5, AICARDI-GOUTIERES SYNDROME 5 (disorder)

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Introduction

A genetic condition usually inherited in an autosomal recessive pattern. It is cause by mutation(s) in the SAMHD1 gene, encoding deoxynucleoside triphosphate triphosphohydrolase SAMHD1. Clinical features and onset may vary significantly, but is characterized in its most severe form by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, and increased concentrations of CSF alpha-interferon.

100 Clinical Results associated with Aicardi-Goutieres Syndrome 5

100 Translational Medicine associated with Aicardi-Goutieres Syndrome 5

0 Patents (Medical) associated with Aicardi-Goutieres Syndrome 5

Literatures (Medical) associated with Aicardi-Goutieres Syndrome 5

12 Jun 2023·Biomedicines

Juvenile Dermatomyositis and Infantile Cerebral Palsy: Aicardi-Gouteres Syndrome, Type 5, with a Novel Mutation in SAMHD1-A Case Report.

Author: Kostik, Mikhail M ; Raupov, Rinat K ; Sorokina, Lubov S

INTRODUCTIONAicardi-Gouteres syndrome (AGS) is a monogenic interferonopathy characterized by early onset, dysregulation of skin (chilblain lesions), brain, and immune systems (fever, hepatomegaly, glaucoma, arthritis, myositis, and autoimmune activity). The disease looks like TORCH (Toxoplasmosis, Others, Rubella, Cytomegalovirus, Herpes) infection with early-onset encephalopathy resulting in severe neuropsychological disability.CASE DESCRIPTIONA six-year-old girl has been suffering from generalized seizures, fever episodes, severe psychomotor development delay, and spastic tetraparesis since the first year of her life. Her two elder brothers died at a young age from suspected infantile cerebral palsy (ICP). Other siblings (younger brother and two elder sisters) are as healthy as their parents. The girl was diagnosed with juvenile dermatomyositis at 5.5 years. Basal ganglia, periventricular, and cerebellum calcifications; hypoplasia of the corpus callosum; and leukodystrophy were detected on CT. The IFN-I score was 12 times higher than normal. The previously not described nucleotide variant c.434G > C (chr 20:36935104C > G; NM_015474) was detected in exon 4 of the SAMHD1 gene in the homozygous state, leading to amino acid substitution p.R145P. Aicardi-Goutières syndrome 5 was diagnosed. Her treatment included corticosteroids, methotrexate, and tofacitinib 5 mg twice a day and it contributed to health improvements. The following brain CT depicted the previously discovered changes without the sign of calcification spreading.CONCLUSIONSEarly diagnosis of AGS is highly important as it allows starting treatment in a timely manner. Timely treatment, in return, can help avoid the development/progression of end-organ damage, including severe neurological complications and early death. It is necessary to spread information about AGS among neurologists, neonatologists, infectious disease specialists, and pediatricians. A multidisciplinary team approach is required.

01 Jan 2023·Human Genetics and Genomics Advances

Whole-exome sequencing in 415,422 individuals identifies rare variants associated with mitochondrial DNA copy number

Article

Author: Arking, Dan E ; Yang, Stephanie ; Guallar, Eliseo ; Pillalamarri, Vamsee ; Say, Conrad ; Lane, John ; Shi, Wen ; Pankratz, Nathan

Inter-individual variation in the number of copies of the mitochondrial genome, called mitochondrial DNA copy number (mtDNA-CN), reflects mitochondrial function and has been associated with various aging-related diseases. We examined 415,422 exomes of self-reported White ancestry individuals from the UK Biobank and tested the impact of rare variants, at the level of single variants and through aggregate variant-set tests, on mtDNA-CN. A survey across nine variant sets tested enrichment of putatively causal variants and identified 14 genes at experiment-wide significance and three genes at marginal significance. These included associations at known mtDNA depletion syndrome genes (mtDNA helicase TWNK, p = 1.1 × 10^-30; mitochondrial transcription factor TFAM, p = 4.3 × 10^-15; mtDNA maintenance exonuclease MGME1, p = 2.0 × 10^-6) and the V617F dominant gain-of-function mutation in the tyrosine kinase JAK2 (p = 2.7 × 10^-17), associated with myeloproliferative disease. Novel genes included the ATP-dependent protease CLPX (p = 8.4 × 10^-9), involved in mitochondrial proteome quality, and the mitochondrial adenylate kinase AK2 (p = 4.7 × 10^-8), involved in hematopoiesis. The most significant association was a missense variant in SAMHD1 (p = 4.2 × 10^-28), found on a rare, 1.2-Mb shared ancestral haplotype on chromosome 20. SAMHD1 encodes a cytoplasmic host restriction factor involved in viral defense response and the mitochondrial nucleotide salvage pathway, and is associated with Aicardi-Goutières syndrome 5, a childhood encephalopathy and chronic inflammatory response disorder. Rare variants were enriched in Mendelian mtDNA depletion syndrome loci, and these variants implicated core processes in mtDNA replication, nucleoid structure formation, and maintenance. These data indicate that strong-effect mutations from the nuclear genome contribute to the genetic architecture of mtDNA-CN.

01 Oct 2022·Stem Cell Research

Generation of induced pluripotent stem cell lines from three patients with Aicardi-Goutières syndrome type 5 due to biallelic SAMDH1 mutations

Article

Author: Hänchen, Vanessa ; Lee-Kirsch, Min Ae ; Wolf, Christine ; Khattak, Shahryar ; Kretschmer, Stefanie ; Neumann, Katrin ; Engel, Kerstin

Mutations in SAMHD1, encoding SAM and HD domain-containing protein 1, cause Aicardi-Goutières syndrome (AGS) 5, an infancy-onset autoinflammatory disease characterized by neurodegeneration and chronic activation of type I interferon. Here, we report the generation and characterization of induced pluripotent stem cells (iPSCs) derived from fibroblasts and peripheral blood mononuclear cells from three AGS patients with biallelic SAMHD1 mutations. These cell lines provide a valuable source to study disease mechanisms and to assess therapeutic molecules.

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Aicardi-Goutieres Syndrome 5

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