ArticleJournal of clinical immunology2022
Mutations in RNU7-1 Weaken Secondary RNA Structure, Induce MCP-1 and CXCL10 in CSF, and Result in Aicardi-Goutières Syndrome with Severe End-Organ Involvement.
Article in Journal of clinical immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 21 citations in OpenAlex.
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- Type I Interferonopathies: Fifteen Years On, From Concept to Therapeutic Perspectives.Current rheumatology reports · 2026Review
- Biallelic variants in RNU2-2 cause a remarkably frequent developmental and epileptic encephalopathy.Nature genetics · 2026Article
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- cGAS inhibitor IMSB301 modifies interferon signalling in peripheral mononuclear cells ofClinical & translational immunology · 2026Article
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- Small nuclear RNA genes in Mendelian disorders.Nature genetics · 2026Review
- Deep Brain Stimulation in a Child with Aicardi-Goutières Syndrome-7 (AGS7): A Case Report and Literature Review.Movement disorders clinical practice · 2025Article
- Human inborn errors of immunity: 2024 update on the classification from the International Union of Immunological Societies Expert Committee.Journal of human immunity · 2025Article
- Emerging concepts and treatments in autoinflammatory interferonopathies and monogenic systemic lupus erythematosus.Nature reviews. Rheumatology · 2025Review
- The prototypical interferonopathy: Aicardi-Goutières syndrome from bedside to bench.Immunological reviews · 2024Review
- The riddle of recurrent fever: a clinical approach to pediatric autoinflammatory diseases.Frontiers in pediatrics · 2024Review
- lhCLIP reveals the in vivo RNA-RNA interactions recognized by hnRNPK.PLoS genetics · 2023Article
- Significance of the cGAS-STING Pathway in Health and Disease.International journal of molecular sciences · 2023Review
- Exome Sequencing and Multigene Panel Testing in 1,411 Patients With Adult-Onset Neurologic Disorders.Neurology. Genetics · 2023Article
- A zebrafish model of Ifih1-driven Aicardi-Goutières syndrome reproduces the interferon signature and the exacerbated inflammation of patients.Frontiers in immunology · 2023Article
- Article
- SMN controls neuromuscular junction integrity through U7 snRNP.Cell reports · 2022Article
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Authors and funding
25 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAicardi-Goutières syndrome (AGS) is a type I interferonopathy usually characterized by early-onset neurologic regression. Biallelic mutations in LSM11 and RNU7-1, components of the U7 small nuclear ribonucleoprotein (snRNP) complex, have been identified in a limited number of genetically unexplained AGS cases. Impairment of U7 snRNP function results in misprocessing of replication-dependent histone (RDH) pre-mRNA and disturbance of histone occupancy of nuclear DNA, ultimately driving cGAS-dependent type I interferon (IFN-I) release.
objectiveWe performed a clinical, genetic, and immunological workup of 3 unrelated patients with uncharacterized AGS.
methodsWhole exome sequencing (WES) and targeted Sanger sequencing of RNU7-1 were performed. Primary fibroblasts were used for mechanistic studies. IFN-I signature and STAT1/2 phosphorylation were assessed in peripheral blood. Cytokines were profiled on serum and cerebrospinal fluid (CSF). Histopathology was examined on brain and kidney tissue.
resultsSequencing revealed compound heterozygous RNU7-1 mutations, resulting in impaired RDH pre-mRNA processing. The 3' stem-loop mutations reduced stability of the secondary U7 snRNA structure. A discrete IFN-I signature in peripheral blood was paralleled by MCP-1 (CCL2) and CXCL10 upregulation in CSF. Histopathological analysis of the kidney showed thrombotic microangiopathy. We observed dysregulated STAT phosphorylation upon cytokine stimulation. Clinical overview of all reported patients with RNU7-1-related disease revealed high mortality and high incidence of organ involvement compared to other AGS genotypes.
conclusionsTargeted RNU7-1 sequencing is recommended in genetically unexplained AGS cases. CSF cytokine profiling represents an additional diagnostic tool to identify aberrant IFN-I signaling. Clinical follow-up of RNU7-1-mutated patients should include screening for severe end-organ involvement including liver disease and nephropathy.
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