ArticleNature genetics2020
cGAS-mediated induction of type I interferon due to inborn errors of histone pre-mRNA processing.
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Article in Nature genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
127citing papers in PubMed, 1 pooled it
8.9field-weighted citation impact, top 1% of its field
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
127 citing papers in PubMed, 1 synthesis or guideline pooled it, 188 citations in OpenAlex.
- The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS.Annals of the rheumatic diseases · 2022Pooled it
- Epigenetic insights into extreme longevity in the world's oldest terrestrial animal, Jonathan.Science advances · 2026Article
- Whole-genome discovery of pathogenic snRNA variants and efficient extended-exome screening.iScience · 2026Article
- Are components of the histone gene expression machinery functionally repurposed in terminally differentiated cells?Biology open · 2026Article
- Movement Disorders in Aicardi-Goutières Syndrome and Response to Immunomodulation.Annals of clinical and translational neurology · 2026Article
- Type I Interferonopathies: Fifteen Years On, From Concept to Therapeutic Perspectives.Current rheumatology reports · 2026Review
- Translating transcriptomics analysis into diagnostic workflows: clinical variant identification and interpretation in hypothesis-driven and hypothesis-free approaches.EBioMedicine · 2026Article
- Expanding roles of cGAS-STING signaling in neuroinflammation.The Journal of clinical investigation · 2026Review
- Article
- No Correlation Between Interferon Signaling and Cytosolic Mitochondrial DNA/RNA Leakage in Cultured Skin Fibroblasts of Patients With Mitochondrial Diseases.European journal of immunology · 2026Article
- A manually curated gene-phenotype catalogue for progeroid syndromes and premature aging.Aging · 2026Article
- Pharmacological stabilization of hypoxia-inducible factor 1-α dampens the interferon response and promotes glycolysis in Aicardi-Goutières syndrome.Nature communications · 2026Article
- A novel patient-Centered approach to clinical trial readiness in rare diseases: Application in Aicardi-Goutières Syndrome (AGS).Molecular genetics and metabolism · 2026Article
- HeterozygousiScience · 2026Article
- Precise control of transcription condensates across S phase balances linker histone expression with DNA replication, ensuring genome stability.Molecular cell · 2026Article
- Retinal Vasculopathy With Cerebral Leukoencephalopathy Mimicking a Brain Tumor: A Case Report.Cureus · 2026Article
- Triazole-based STING inhibitors.Bioorganic & medicinal chemistry · 2026Article
- A homozygous splice-site variant in SAMHD1 shows variable expressivity of Aicardi-Goutières syndrome type 5: a case report and literature review.Frontiers in pediatrics · 2026Article
- Small nuclear RNA genes in Mendelian disorders.Nature genetics · 2026Review
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
67 more citing papers are in PubMed but not listed here.
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Authors and funding
56 authors at 20 institutions in 8 countries.
Carolina UggentiCentre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
Alice Lepelley *University of Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, Paris, France.ORCID http://orcid.org/0000-0001-8656-7291
Marine Depp *Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
Andrew P Badrock *Centre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
Mathieu P RoderoUniversity of Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, Paris, France.
Marie-Thérèse El-DaherCentre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
Gillian I RiceDivision of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.ORCID http://orcid.org/0000-0002-4223-0571
Somdutta DhirCentre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
Ann P WheelerMedical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
Ashish DhirCentre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
Waad AlbawardiMedical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
Marie-Louise FrémondUniversity of Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, Paris, France.
Luis SeabraUniversity of Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, Paris, France.ORCID http://orcid.org/0000-0002-4678-3026
Jennifer DoigCentre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
Natalie BlairCentre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
Maria José Martin-NiclosUniversity of Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, Paris, France.
Erika Della MinaUniversity of Paris, Imagine Institute, Laboratory of Neurogenetics and Neuroinflammation, Paris, France.ORCID http://orcid.org/0000-0001-8733-7623
Alejandro Rubio-RoldánCentre for Genomics and Oncological Research (GENyO), Pfizer-University of Granada-Andalusian Regional Government, Parque Tecnico de la Ciencia de Salud, Granada, Spain.ORCID http://orcid.org/0000-0002-6775-4013
Jose L García-PérezMedical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-8132-9849
Duncan SproulMedical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0001-6168-4563
Jan RehwinkelMedical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Jonny HertzogMedical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-7089-982X
Anne Boland-AugeUniversité Paris-Saclay, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Centre National de Recherche en Génomique Humaine, Évry, France.ORCID http://orcid.org/0000-0001-8789-5676
Robert OlasoUniversité Paris-Saclay, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Centre National de Recherche en Génomique Humaine, Évry, France.
Jean-François DeleuzeUniversité Paris-Saclay, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Centre National de Recherche en Génomique Humaine, Évry, France.ORCID http://orcid.org/0000-0002-5358-4463
Julien BaruteauUniversity College London Great Ormond Street Institute of Child Health, London, UK.ORCID http://orcid.org/0000-0003-0582-540X
Karine BrochardService de Médecine Interne Néphrologie Pédiatrique, Hôpital des Enfants, Toulouse, France.
Jonathan BuckleyDepartment of Paediatric Nephrology, University of Cape Town, Red Cross War Memorial Children's Hospital, Cape Town, South Africa.
Vanessa CavalleraChild Neurology and Psychiatry Unit, Istituto di Ricovero e Cura a Carattere Scientifico, Mondino Foundation, Pavia, Italy.
Cristina CeredaGenomic and Post-Genomic Center, Istituto di Ricovero e Cura a Carattere Scientifico, Mondino Foundation, Pavia, Italy.
Liesbeth M H De WaeleDepartment of Paediatric Neurology, University Hospitals Leuven, Leuven, Belgium.
Angus DobbieYorkshire Clinical Genetics Service, Chapel Allerton Hospital, Leeds, UK.
Diane DoummarSorbonne Université, Assistance Publique-Hôpitaux de Paris, Département de Neuropédiatrie, Centre de Référence de Neurogénétique et Mouvements Anormaux de l'Enfant, Hôpital Armand Trousseau, Paris, France.
Frances ElmslieSouth West Thames Regional Genetics Service, St George's, University of London, London, UK.
Margarete Koch-HogrebeDepartment of Paediatric Neurology, Children's Hospital Datteln, Witten/Herdecke University, Datteln, Germany.
Ram KumarDepartment of Paediatric Neurology, Alder Hey Children's National Health Service Foundation Trust, Liverpool, UK.
Kate LambDepartment of Paediatrics, Gloucestershire Royal Hospital, Gloucester, UK.
John H LivingstonDepartment of Paediatric Neurology, Leeds Teaching Hospitals National Health Service Trust, Leeds, UK.ORCID http://orcid.org/0000-0002-4017-0667
Anirban MajumdarDepartment of Paediatric Neurology, Bristol Children's Hospital, Bristol, UK.
Charles Marques LorençoFaculdade de Medicina - Centro Universitário Estácio de Ribeirão Preto, Ribeirão Preto, Brazil.
Simona OrcesiChild Neurology and Psychiatry Unit, Istituto di Ricovero e Cura a Carattere Scientifico, Mondino Foundation, Pavia, Italy.ORCID http://orcid.org/0000-0001-8947-9342
Sylviane PeudenierCentre de Référence des Déficiences Intellectuelles de Causes Rares et Polyhandicap, Centre Hospitalier Régional Universitaire de Brest, Brest, France.
Kevin RostasyDepartment of Paediatric Neurology, Children's Hospital Datteln, Witten/Herdecke University, Datteln, Germany.
Caroline A SalmonDepartment of Paediatrics, Royal Surrey County Hospital, Guildford, UK.
Christiaan ScottUniversity of Cape Town, Red Cross War Memorial Children's Hospital, Cape Town, South Africa.ORCID http://orcid.org/0000-0003-3874-1704
Davide TondutiCenter for diagnosis and treatment of Leukodystrophies, Pediatric Neurology Unit, V. Buzzi Children's Hospital, Milano, Italy.ORCID http://orcid.org/0000-0001-9371-7454
Guy TouatiReference Center for Inborn Errors of Metabolism-Department of Pediatrics, Hôpital des Enfants-Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
Marialuisa ValenteGenomic and Post-Genomic Center, Istituto di Ricovero e Cura a Carattere Scientifico, Mondino Foundation, Pavia, Italy.
Hélio van der LindenDepartment of Paediatric Neurology, Neurological Institute of Goiânia, Goiânia, Brazil.
Hilde Van EschCenter for Human Genetics, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.
Marie VermelleDepartment of Paediatrics, Centre Hospitalier de Dunkerque, Dunkerque, France.
Kate WebbUniversity of Cape Town, Red Cross War Memorial Children's Hospital, Cape Town, South Africa.ORCID http://orcid.org/0000-0003-1087-5946
Andrew P JacksonMedical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
Martin A M ReijnsMedical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-5048-2752
Nick GilbertMedical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0003-0505-6081
Yanick J CrowCentre for Genomic and Experimental Medicine, Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK. yanickcrow@mac.com.ORCID http://orcid.org/0000-0001-7211-7564
Edinburgh College · GBUniversité Paris Cité · FRCommissariat à l'Énergie Atomique et aux Énergies Alternatives · FRUniversity of Cape Town · ZACenter for Genomic Science · ITCentre Hospitalier Universitaire de Toulouse · FREdinburgh Cancer Research · GBKU Leuven · BEUniversity of Oxford · GBWitten/Herdecke University · DEBristol Royal Hospital for Children · GBCentre Hospitalier Régional Universitaire de Brest · FRChapel Allerton Hospital · GBCTO Hospital · ITGloucestershire Hospitals NHS Foundation Trust · GBGreat Ormond Street Hospital · GBIkerbasque · ESIstituti di Ricovero e Cura a Carattere Scientifico · ITLeeds Teaching Hospitals NHS Trust · GBManchester Academic Health Science Centre · GB
Funding
Cancer Research UK 20837Cancer Research UK C47648/A20837Department of HealthMedical Research Council MC_UU_00007/13Medical Research Council MC_UU_00007/5Medical Research Council MC_UU_00008/8Medical Research Council MR/P028071/1Medical Research Council U127580972Wellcome Trust 208345/Z/17/Z
Abstract
Inappropriate stimulation or defective negative regulation of the type I interferon response can lead to autoinflammation. In genetically uncharacterized cases of the type I interferonopathy Aicardi-Goutières syndrome, we identified biallelic mutations in LSM11 and RNU7-1, which encode components of the replication-dependent histone pre-mRNA-processing complex. Mutations were associated with the misprocessing of canonical histone transcripts and a disturbance of linker histone stoichiometry. Additionally, we observed an altered distribution of nuclear cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) and enhanced interferon signaling mediated by the cGAS-stimulator of interferon genes (STING) pathway in patient-derived fibroblasts. Finally, we established that chromatin without linker histone stimulates cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) production in vitro more efficiently. We conclude that nuclear histones, as key constituents of chromatin, are essential in suppressing the immunogenicity of self-DNA.
Indexed as
Autoimmune Diseases of the Nervous SystemCell LineChromatinCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDNAGene Expression RegulationHCT116 CellsHEK293 CellsHereditary Autoinflammatory DiseasesHistonesHumansInterferon Type IMembrane ProteinsNervous System MalformationsNucleotides, CyclicNucleotidyltransferasescGAS protein, humanChromatincyclic guanosine monophosphate-adenosine monophosphateCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDNAHistonesInterferon Type ILSM11 protein, humanMembrane ProteinsNucleotides, CyclicNucleotidyltransferasesRibonucleoprotein, U7 Small NuclearRNA-Binding ProteinsRNA PrecursorsSTING1 protein, humanSTING Protein
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