{
  "abstract": "Defects in transcription and DNA repair pathways underlie a growing spectrum of rare neurodevelopmental disorders, including MEDopathies and transcription-coupled repair (TCR)-related syndromes like Cockayne Syndrome (CS). Here, we report biallelic variants in MED20, encoding a core subunit of Mediator, in eight individuals presenting intellectual disability, brain atrophy, dystonia and developmental delay. Patient-derived fibroblasts exhibit mild but consistent defects in TCR, alongside transcriptional abnormalities reminiscent of CS. Functional modeling of MED20 variants in yeast and nematode recapitulates UV sensitivity, transcriptional impairment and neurodevelopmental defects. At the molecular level, MED20 variants disrupt interactions within the Mediator complex, disturbing the pre-initiation complex and reducing transcriptional output. Collectively, these findings identify MED20 pathogenic variants as a cause of neurodevelopmental disorder at the interface of transcription and DNA repair and position Mediator-dependent transcriptional regulation upstream of TCR. This work establishes a direct link between inherited defects in basal transcription machinery and human transcription-DNA repair syndromes.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 34,
  "authors": [
    {
      "name": "Nicolas Le May"
    },
    {
      "name": "Raphaël Leconte"
    },
    {
      "name": "Adriana Alberti"
    },
    {
      "name": "Valeria Ramirez-Ramirez"
    },
    {
      "name": "Thanh Vuong-Bender"
    },
    {
      "name": "Judit Osz"
    },
    {
      "name": "Eléonore Réal"
    },
    {
      "name": "Christelle Maalouf"
    },
    {
      "name": "Carole Peluso-Iltis"
    },
    {
      "name": "Cathy Obringer"
    },
    {
      "name": "Sylviane Peudenier"
    },
    {
      "name": "Moustapha Ndiaye"
    },
    {
      "name": "Marietou Traore"
    },
    {
      "name": "Ainara Salazar-Villacorta"
    },
    {
      "name": "Shira Ziegler"
    },
    {
      "name": "Carolyn Applegate"
    },
    {
      "name": "Ada Hamosh"
    },
    {
      "name": "Imène Boujelbene"
    },
    {
      "name": "Samuel Nicaise"
    },
    {
      "name": "Elise Hameau"
    },
    {
      "name": "Sophie Scheidecker"
    },
    {
      "name": "Gaétan Caravello"
    },
    {
      "name": "Véronique Geoffroy"
    },
    {
      "name": "Jean Muller"
    },
    {
      "name": "Hélène Dollfus"
    },
    {
      "name": "Pedro Rodriguez Cruz"
    },
    {
      "name": "Ingrid Wentzensen"
    },
    {
      "name": "Julia Vodopiutz"
    },
    {
      "name": "Andreas Janecke"
    },
    {
      "name": "Nadège Calmels"
    },
    {
      "name": "Vincent Laugel"
    },
    {
      "name": "Björn Schumacher"
    },
    {
      "name": "Natacha Rochel"
    },
    {
      "name": "Julie Soutourina"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e8hh5zfz2rsq0.bib",
  "cited_by": 0,
  "doi": "10.21203/rs.3.rs-9516499/v1",
  "fulltext_url": null,
  "id": "e8hh5zfz2rsq0",
  "issns": [],
  "landing_url": "https://hal.science/hal-05780827v1",
  "language": "en",
  "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": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "1312|DNA Repair Mechanisms"
    ]
  ],
  "openalex": "W7163377071",
  "pdf_url": "https://hal.science/hal-05780827/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-06-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e8hh5zfz2rsq0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "hal-05780827",
      "source": "hal",
      "url": "https://hal.science/hal-05780827v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|DNA Repair Mechanisms",
      "subfield": "molecular-biology"
    }
  ],
  "title": "MED20 biallelic pathogenic variants cause a neurodevelopmental disorder altering both transcription activity and Transcription-Coupled Repair pathway",
  "title_text": "MED20 biallelic pathogenic variants cause a neurodevelopmental disorder altering both transcription activity and Transcription-Coupled Repair pathway",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:49Z",
  "url": "https://research.draconitic.com/paper/e8hh5zfz2rsq0",
  "venue": "HAL",
  "versions": []
}