{
  "abstract": "Kabuki syndrome type 1 (KS1) is a rare cause of intellectual disability resulting from heterozygous pathogenic variants in the gene encoding the histone methyltransferase KMT2D. A previously established loss-of-function mouse model of KS1 exhibits key phenotypic features, and therapeutic trials in this mouse model suggest postnatal malleability of neurological symptoms. However, 15-30% of individuals with KS1 carry missense variants. To investigate whether missense variants lead to similar phenotypic presentation in mice, we used CRISPR-Cas9 to introduce the KS1 patient variant R5179H, corresponding to R5230H in mice, into C57BL/6NTac animals. Computational and in vitro testing suggested that the R5230H variant does not impair protein stability or enzyme function of KMT2D. Despite a distinct mechanistic basis, our new mouse model (Kmt2d+/R5230H) recapitulated most phenotypes of our prior loss-of-function model, including growth deficiency, craniofacial anomalies and IgA deficiency, but not altered neurological function. Kmt2d+/R5230H mice showed perinatal lethality and a high frequency of unilateral kidney agenesis, a novel phenotype in KS1 mouse models. Kmt2d+/R5230H mice provide a unique opportunity to understand the impact of missense variants on KMT2D function and uncover developmental and perinatal abnormalities in KS1.",
  "abstract_shown": true,
  "affiliations": [
    "The Louma G. Laboratory of Epigenetic Research, Faculty of Medicine, University of Iceland, Reykjavik 102, Iceland",
    "Department of Genetics and Molecular Medicine, Landspitali University Hospital, Reykjavik 101, Iceland",
    "McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA",
    "Department of Pediatrics, Johns Hopkins University, Baltimore, MD 21205, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Sara Tholl Halldorsdottir",
      "orcid": "0009-0008-5844-5447"
    },
    {
      "affs": [
        0
      ],
      "name": "Meghna Vinod",
      "orcid": "0009-0008-9057-6834"
    },
    {
      "affs": [
        0
      ],
      "name": "Hilmar Orn Gunnlaugsson"
    },
    {
      "affs": [
        0
      ],
      "name": "Ellen Dagmar Bjornsdottir",
      "orcid": "0009-0005-8628-0000"
    },
    {
      "affs": [
        0
      ],
      "name": "Romain Maurice Jacques Lasseur",
      "orcid": "0000-0003-0729-4841"
    },
    {
      "affs": [
        2
      ],
      "name": "Teresa Luperchio",
      "orcid": "0000-0001-8586-3101"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Jill A. Fahrner",
      "orcid": "0000-0001-5506-8780"
    },
    {
      "affs": [
        0
      ],
      "name": "Agnes Ulfig",
      "orcid": "0000-0003-2689-6311"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Hans Tomas Bjornsson",
      "orcid": "0000-0001-6635-6753"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ee88sr22y6yey.bib",
  "cited_by": 0,
  "doi": "10.1242/dmm.052775",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13714867/",
  "id": "ee88sr22y6yey",
  "issns": [
    "1754-8403",
    "1754-8411"
  ],
  "landing_url": "https://doi.org/10.1242/dmm.052775",
  "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": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "1311|Genetics and Neurodevelopmental Disorders"
    ]
  ],
  "openalex": "W4416340526",
  "pdf_url": null,
  "pmcid": "PMC13714867",
  "pmid": "42713652",
  "published": "2026-10-14",
  "publisher": "Company of Biologists",
  "ris": "https://research.draconitic.com/paper/ee88sr22y6yey.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:22:17Z",
      "native_id": "PMC13714867",
      "source": "pmc",
      "url": "https://doi.org/10.1242/dmm.052775"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Genetics and Neurodevelopmental Disorders",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "A patient-derived missense mouse model of Kabuki syndrome 1",
  "title_text": "A patient-derived missense mouse model of Kabuki syndrome 1",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:17Z",
  "url": "https://research.draconitic.com/paper/ee88sr22y6yey",
  "venue": "Disease Models & Mechanisms",
  "versions": []
}