{
  "abstract": "The X-linked α-thalassaemia intellectual disability syndrome (ATRX) protein is a chromatin remodeller involved in transcriptional regulation and genome stability. While the importance of ATRX in development and malignancy is well recognised, its role in innate immunity is less well defined. Here we describe three unrelated patients with ATR-X syndrome carrying missense mutations in the ATPase domain of ATRX, each manifesting features of severe inflammation accompanied by persistent upregulation of interferon-stimulated gene expression in whole blood. Studies in patient-derived cells, CRISPR-engineered fibroblasts and neuronal models demonstrate that ATRX loss-of-function mutations drive enhanced type I interferon signalling through a cGAS-dependent mechanism uncoupled from the DNA sensing activity of cGAS. Mechanistically, ATRX deficiency disrupts the chromatin distribution of DAXX and H3.3, with cGAS essential for the changes in nucleosome composition and gene expression mediated by loss of ATRX. Thus, our study highlights a link between ATRX dysfunction and inflammation involving a non-canonical role of cGAS.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 34,
  "authors": [
    {
      "name": "Marie-Thérèse A. El-Daher",
      "orcid": "0000-0001-7166-2763"
    },
    {
      "name": "Eve L. White"
    },
    {
      "name": "Andreas Fellas"
    },
    {
      "name": "Graeme Grimes"
    },
    {
      "name": "Simone Pelliciari",
      "orcid": "0000-0003-3150-9136"
    },
    {
      "name": "Gaofeng Zhu",
      "orcid": "0009-0008-3382-0204"
    },
    {
      "name": "Tom A. Tait"
    },
    {
      "name": "Carolina Uggenti"
    },
    {
      "name": "Natalie Blair"
    },
    {
      "name": "Erisa Nita"
    },
    {
      "name": "Philippe Gautier"
    },
    {
      "name": "Hywel Dunn-Davies",
      "orcid": "0000-0003-3975-788X"
    },
    {
      "name": "Sophie Glen"
    },
    {
      "name": "Somdutta Dhir"
    },
    {
      "name": "Mathieu P. Rodero"
    },
    {
      "name": "Gillian I. Rice",
      "orcid": "0000-0002-4223-0571"
    },
    {
      "name": "Luis Seabra",
      "orcid": "0000-0002-4678-3026"
    },
    {
      "name": "Richard Clark",
      "orcid": "0000-0002-0066-1541"
    },
    {
      "name": "Angie Fawkes"
    },
    {
      "name": "Joseph A. Marsh",
      "orcid": "0000-0003-4132-0628"
    },
    {
      "name": "Minke HW Huibers"
    },
    {
      "name": "Joost B. Koedijk"
    },
    {
      "name": "Erika Van Nieuwenhove"
    },
    {
      "name": "John H. Livingston"
    },
    {
      "name": "Evangeline Wassmer",
      "orcid": "0000-0002-2446-1106"
    },
    {
      "name": "Swati Naik"
    },
    {
      "name": "Julie Vogt"
    },
    {
      "name": "Bertrand Isidor"
    },
    {
      "name": "Tom D. Deegan"
    },
    {
      "name": "Alice Lepelley",
      "orcid": "0000-0001-8656-7291"
    },
    {
      "name": "Rebekah Tillotson",
      "orcid": "0000-0003-2863-4569"
    },
    {
      "name": "Patrick Revy",
      "orcid": "0000-0003-0758-8022"
    },
    {
      "name": "Richard J. Gibbons"
    },
    {
      "name": "Yanick J. Crow",
      "orcid": "0000-0001-7211-7564"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/52nzsyfe0smh6.bib",
  "cited_by": 2,
  "doi": "10.1038/s41467-026-78094-8",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7619637/?tool=EBI",
  "id": "52nzsyfe0smh6",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://www.nature.com/articles/s41467-026-78094-8",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|interferon and immune responses"
    ]
  ],
  "openalex": "W7220973690",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7619637/pdf/?tool=EBI",
  "pmcid": "PMC7619637",
  "pmid": null,
  "published": "2026-10-08",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/52nzsyfe0smh6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:38Z",
      "native_id": "10.1038/s41467-026-78094-8",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41467-026-78094-8"
    },
    {
      "first_seen": "2026-10-30T12:20:32Z",
      "native_id": "PMC:PMC7619637",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC7619637"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|interferon and immune responses",
      "subfield": "immunology"
    }
  ],
  "title": "ATRX deficiency drives aberrant type I interferon signalling through cGAS-dependent transcriptional dysregulation",
  "title_text": "ATRX deficiency drives aberrant type I interferon signalling through cGAS-dependent transcriptional dysregulation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:32Z",
  "url": "https://research.draconitic.com/paper/52nzsyfe0smh6",
  "venue": "Nature Communications",
  "versions": []
}