{
  "abstract": "Chromatin remodelers are increasingly recognized as key contributors to neurodevelopmental disorders, usually through de novo dominant variants. Mortality Factor 4 Like 1 (MORF4L1) is recognized for its role in chromatin organization and transcriptional regulation. We identified a consanguineous Middle Eastern family in which a neurodevelopmental disorder with a distinctive dysmorphic phenotype segregated with a homozygous variant in MORF4L1. The autosomal recessive inheritance sets it apart from most other chromatin remodeling disorders. Consistent with its epigenetic role, we also observed a disruption in DNA methylation patterns in patient blood compared to controls. We modelled both the patient variant and a predicted loss of function variant in zebrafish and found that biallelic loss of function fish exhibited growth restriction and craniofacial/skeletal defects consistent with the patients’ phenotypes. Surprisingly, larvae with knock in of the mutant morf4l1 KI/KI appeared phenotypically normal with respect to jaw development suggesting that the impact of the variant is less severe in zebrafish. Functional modelling in zebrafish confirms a loss‑of‑function mechanism and highlights species‑dependent differences specifically in the impact of the missense variant on protein function. The tolerance of zebrafish to the human variant provides a cautionary tale about overreliance on animal models as a screening tool for variant classification.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Translational Genomics, Genomic Medicine Centre of Excellence, King Faisal Specialist Hospital and Research Center",
    "Department of Pediatrics, Faculty of Medicine, Kuwait University",
    "Neuroscience Centre, King Faisal Specialist Hospital and Research Centre",
    "Program in Developmental and Stem Cell Biology, SickKids Research Institute",
    "Kuwait Medical Genetics Centre, Ministry of Health",
    "Zebrafish Genetics and Disease Model Core, SickKids Research Institute"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hanan E. Shamseldin"
    },
    {
      "affs": [
        1
      ],
      "name": "Dana Marafi"
    },
    {
      "affs": [
        2
      ],
      "name": "Mohammed AlMuhaizea"
    },
    {
      "affs": [
        3
      ],
      "name": "C’airah Ceolin"
    },
    {
      "affs": [
        0
      ],
      "name": "Firdous Abdulwahab"
    },
    {
      "affs": [
        0
      ],
      "name": "Tarfa Alshidi"
    },
    {
      "affs": [
        4
      ],
      "name": "Buthaina Albash"
    },
    {
      "affs": [
        1
      ],
      "name": "Fatemah Alabdulrazzaq"
    },
    {
      "affs": [
        3
      ],
      "name": "Harsha R. Murthy"
    },
    {
      "affs": [
        3
      ],
      "name": "Jenica L. M. Van Gennip"
    },
    {
      "affs": [
        3
      ],
      "name": "Isabella M. Harmic"
    },
    {
      "affs": [
        5
      ],
      "name": "Rebecca Simonian"
    },
    {
      "affs": [
        5
      ],
      "name": "Xiucheng Cui"
    },
    {
      "affs": [
        5
      ],
      "name": "Jason Burgess"
    },
    {
      "affs": [
        3
      ],
      "name": "Brian Ciruna"
    },
    {
      "affs": [
        3
      ],
      "name": "Ashish R. Deshwar"
    },
    {
      "affs": [
        0
      ],
      "name": "Fowzan S. Alkuraya"
    },
    {
      "affs": [
        0
      ],
      "name": "Lama AlAbdi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5qdd3rs4013ea.bib",
  "cited_by": 0,
  "doi": "10.1038/s41598-026-61907-7",
  "fulltext_url": "https://doi.org/10.1038/s41598-026-61907-7",
  "id": "5qdd3rs4013ea",
  "issns": [
    "2045-2322"
  ],
  "landing_url": "https://doi.org/10.1038/s41598-026-61907-7",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "Q"
    ],
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "1311|Genetics and Neurodevelopmental Disorders"
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  "openalex": "W7168428219",
  "pdf_url": "https://www.nature.com/articles/s41598-026-61907-7_reference.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-01",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/5qdd3rs4013ea.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:45:46Z",
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      "url": "https://doi.org/10.1038/s41598-026-61907-7"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Genetics and Neurodevelopmental Disorders",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "MORF4L1, encoding a chromatin remodeler, is mutated in a recognizable dysmorphic neurodevelopmental disorder",
  "title_text": "MORF4L1, encoding a chromatin remodeler, is mutated in a recognizable dysmorphic neurodevelopmental disorder",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:46Z",
  "url": "https://research.draconitic.com/paper/5qdd3rs4013ea",
  "venue": "Scientific Reports",
  "versions": []
}