|
rs121908117
|
|
|
0.030 |
GeneticVariation |
BEFREE |
The X-ray crystal structures of the TREX1 wt apoprotein, the dominant D200H, D200N and D18N homodimer mutants derived from AGS and FCL patients, as well as the recessive V201D homodimer mutant have been determined.
|
22071149 |
2012 |
|
rs121908117
|
|
|
0.030 |
GeneticVariation |
BEFREE |
A de novo p.Asp18Asn mutation in TREX1 in a patient with Aicardi-Goutières syndrome.
|
20799324 |
2010 |
|
rs121908117
|
|
|
0.030 |
GeneticVariation |
BEFREE |
Further, the D200N- and D18N-containing TREX1 homo- and heterodimers inhibit the dsDNA degradation activity of TREX1WT enzyme, providing a likely explanation for the dominant phenotype of these TREX1 mutant alleles in AGS and FCL.
|
18805785 |
2008 |
|
rs72556554
|
|
|
0.030 |
GeneticVariation |
BEFREE |
Here we describe a patient with AGS due to a homozygous p.Arg114His mutation in the TREX1 gene.
|
28089741 |
2017 |
|
rs72556554
|
|
|
0.030 |
GeneticVariation |
BEFREE |
The TREX1 proteins containing R114H and the insertion mutations aspartate at position 201 (D201ins) and alanine at position 124 (A124ins), found in compound heterozygous AGS with R114H, were prepared and the DNA degradation activities were tested.
|
21937424 |
2011 |
|
rs72556554
|
|
|
0.030 |
GeneticVariation |
BEFREE |
By comparison, the TREX1 R114H homozygous mutation causes AGS and is found as a heterozygous mutation in systemic lupus erythematosus.
|
18805785 |
2008 |
|
rs78635798
|
|
|
0.030 |
GeneticVariation |
BEFREE |
Moreover, of five analyzed mutations in human RNASEH2B and RNASEH2C linked to Aicardi-Goutières Syndrome (AGS), only one, R69W in the RNASEH2C protein, exhibits a significant reduction in specific activity, revealing a role for the C subunit in enzymatic activity.
|
19015152 |
2009 |
|
rs78635798
|
|
|
0.030 |
GeneticVariation |
BEFREE |
In contrast, the recurrent c.205C > T (p.R69W) RNASEH2C Asian founder mutation has previously only been identified in children with a severe AGS phenotype.
|
23322642 |
2013 |
|
rs78635798
|
|
|
0.030 |
GeneticVariation |
BEFREE |
p.Arg69Trp in RNASEH2C is a founder variant in three Indian families with Aicardi-Goutières syndrome.
|
29150899 |
2018 |
|
rs267607027
|
|
|
0.020 |
GeneticVariation |
BEFREE |
Next generation sequencing of the entire region identified the c.490C>T (p.Arg164X) mutationin SAMHD1, a gene most recently described in AGS, on both alleles in all affected siblings.Clinical diagnosis of AGS was then confirmed by demonstrating intracerebral calcifications on cranial computed tomography in all siblings and elevated pterin levels in CSF in three of them.
|
20842748 |
2010 |
|
rs267607027
|
|
|
0.020 |
GeneticVariation |
BEFREE |
Primary peripheral blood mononuclear cells (PBMC) from AGS patients homozygous for a nonsense mutation in SAMHD1 (R164X) lacked endogenous SAMHD1 expression and support HIV-1 replication in the absence of exogenous activation.
|
22174685 |
2011 |
|
rs78846775
|
|
|
0.020 |
GeneticVariation |
BEFREE |
Mutations in TREX1 at positions Asp-18 and Asp-200 to His and Asn exhibit dominant autoimmune phenotypes associated with the clinical disorders familial chilblain lupus and Aicardi-Goutières syndrome.
|
24616097 |
2014 |
|
rs78846775
|
|
|
0.020 |
GeneticVariation |
BEFREE |
Further, the D200N- and D18N-containing TREX1 homo- and heterodimers inhibit the dsDNA degradation activity of TREX1WT enzyme, providing a likely explanation for the dominant phenotype of these TREX1 mutant alleles in AGS and FCL.
|
18805785 |
2008 |
|
rs121434516
|
|
|
0.010 |
GeneticVariation |
BEFREE |
Our investigations revealed that the SAMHD1 AGS variant p.G209S preserve all tested biochemical, cellular, and antiviral properties, suggesting that this residue is a determinant for the ability of SAMHD1 to negatively regulate the type I IFN response in human patients with AGS.
|
28229507 |
2017 |
|
rs28939668
|
|
|
0.010 |
GeneticVariation |
BEFREE |
We have studied a JAG1 missense mutation (JAG1-G274D) that was previously identified in 13 individuals from an extended family with cardiac defects of the type seen in patients with AGS (e.g., peripheral pulmonic stenosis and tetralogy of Fallot) in the absence of liver dysfunction.
|
12649809 |
2003 |
|
rs74555752
|
|
|
0.010 |
GeneticVariation |
BEFREE |
The diagnosis of AGS was confirmed by sequence analysis, which identified a previously reported homozygous RNASEH2B mutation, c.554 T > G (p.V185G).
|
28332073 |
2017 |
|
rs75184679
|
|
A |
0.700 |
GeneticVariation |
CLINVAR |
Expanding the phenotypic spectrum of lupus erythematosus in Aicardi-Goutières syndrome.
|
20131292 |
2010 |
|
rs75184679
|
|
A |
0.700 |
GeneticVariation |
CLINVAR |
RNaseH2 mutants that cause Aicardi-Goutieres syndrome are active nucleases.
|
19034401 |
2009 |
|
rs75184679
|
|
A |
0.700 |
GeneticVariation |
CLINVAR |
Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly.
|
26846091 |
2016 |
|
rs75184679
|
|
A |
0.700 |
GeneticVariation |
CLINVAR |
Spastic paraparesis and marked improvement of leukoencephalopathy in Aicardi-Goutières syndrome.
|
25343331 |
2014 |
|
rs75184679
|
|
A |
0.700 |
GeneticVariation |
CLINVAR |
Genome-wide DNA hypomethylation and RNA:DNA hybrid accumulation in Aicardi-Goutières syndrome.
|
26182405 |
2015 |
|
rs75184679
|
|
A |
0.700 |
GeneticVariation |
CLINVAR |
Mutations in ADAR1, IFIH1, and RNASEH2B presenting as spastic paraplegia.
|
25243380 |
2014 |
|
rs75184679
|
|
A |
0.700 |
CausalMutation |
CLINVAR |
Clinical and molecular phenotype of Aicardi-Goutieres syndrome.
|
17846997 |
2007 |
|
rs75184679
|
|
A |
0.700 |
GeneticVariation |
CLINVAR |
Clinical and molecular phenotype of Aicardi-Goutieres syndrome.
|
17846997 |
2007 |
|
rs75184679
|
|
A |
0.700 |
CausalMutation |
CLINVAR |
Mutations in ADAR1, IFIH1, and RNASEH2B presenting as spastic paraplegia.
|
25243380 |
2014 |