{
  "abstract": "Purpose: Defects in components of the CDC45–MCM2-7–GINS (CMG) helicase complex have been associated with natural killer (NK) cell deficiency in rare inborn errors of immunity. Pathogenic biallelic variants in MCM10 have been reported in a limited number of individuals with severe immunologic and developmental phenotypes. We aimed to further delineate the clinical and immunologic spectrum of MCM10 deficiency.\n\nMethods: Singleton exome sequencing, RNA splicing analysis, flow cytometry–based immunophenotyping, telomere length assessment, radiation sensitivity testing, and in silico analysis of publicly available single-cell RNA sequencing datasets were performed.\n\nResults: A six-year-old boy presented with poikiloderma, photosensitivity, growth failure, and immune dysregulation. Exome sequencing identified a homozygous canonical splice-site variant in MCM10 (c.930 + 2T > A), resulting in an in-frame deletion of 17 amino acids within the oligonucleotide/oligosaccharide-binding (OB)-fold domain, confirmed at the RNA level.Immunophenotyping showed near-absent NK cells with increased NK-T cells and terminally differentiated CD8 T cells. While karyotype, telomere length, and radiation sensitivity were normal, limited MCM10 expression in replicating NK cells is suspected. During follow-up, the patient developed an aggressive Epstein–Barr virus–positive squamous cell carcinoma of the tongue, an exceedingly rare childhood malignancy.\n\nConclusion: This case expands the phenotypic spectrum of MCM10-related inborn errors of immunity and supports a critical role for MCM10 in NK-cell development and immune homeostasis. The occurrence of a virus-associated malignancy suggests susceptibility and impaired immune surveillance. Together with previously described defects in CMG-complex components, these findings are consistent with an emerging group of DNA replication–associated immune disorders.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s10875-026-02045-7.",
  "abstract_shown": true,
  "affiliations": [
    "The Genetics Institute and Genomics Center, Tel Aviv Sourasky University Medical Center, 6 Weizmann St, Tel Aviv, 64239 Israel",
    "Gray Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel",
    "Allergy and Clinical Immunology Unit, Department of Medicine, Tel Aviv Sourasky University Medical Center, 6 Weizmann St, Tel Aviv, 64239 Israel",
    "Institute of Pulmonary Medicine, Center of Excellence for Interstitial Lung Diseases, Tel Aviv Sourasky University Medical Center, Tel Aviv, Israel"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yael Hoffman"
    },
    {
      "affs": [
        0
      ],
      "name": "Alina Kurolap"
    },
    {
      "affs": [
        0
      ],
      "name": "Hila Ledermann Nahmias"
    },
    {
      "affs": [
        0
      ],
      "name": "Adi Mory"
    },
    {
      "affs": [
        2
      ],
      "name": "Tal Freund"
    },
    {
      "affs": [
        3,
        1
      ],
      "name": "Avraham Unterman"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Uri Hamiel"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Hagit Baris Feldman"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Daphna Marom"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "David Hagin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/81wcsn25kgrp1.bib",
  "cited_by": 0,
  "doi": "10.1007/s10875-026-02045-7",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710629/",
  "id": "81wcsn25kgrp1",
  "issns": [
    "0271-9142",
    "1573-2592"
  ],
  "landing_url": "https://doi.org/10.1007/s10875-026-02045-7",
  "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"
    ],
    [
      "openalex",
      "2403|Immunodeficiency and Autoimmune Disorders"
    ]
  ],
  "openalex": "W7171641151",
  "pdf_url": null,
  "pmcid": "PMC13710629",
  "pmid": "42934442",
  "published": "2026-07-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/81wcsn25kgrp1.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:33Z",
      "native_id": "PMC13710629",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s10875-026-02045-7"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immunodeficiency and Autoimmune Disorders",
      "subfield": "immunology"
    }
  ],
  "title": "Biallelic MCM10 Deficiency Presenting with Natural Killer Cell Deficiency, Poikiloderma and EBV-Associated Malignancy",
  "title_text": "Biallelic MCM10 Deficiency Presenting with Natural Killer Cell Deficiency, Poikiloderma and EBV-Associated Malignancy",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:33Z",
  "url": "https://research.draconitic.com/paper/81wcsn25kgrp1",
  "venue": "Journal of Clinical Immunology",
  "versions": []
}