{
  "abstract": "Introduction: Esophageal atresia (EA) is a congenital foregut malformation with substantial genetic heterogeneity. While coding variants explain some syndromic cases, the molecular basis of non-syndromic EA remains largely unknown. We investigated an Israeli-Bedouin kindred with a high incidence of non-syndromic EA.\n\nMethods: Three of ten affected individuals underwent whole-exome/genome sequencing. Following variant filtering and prioritization using population databases and in silico tools, the candidate non-coding variant underwent Sanger sequencing in all five available affected individuals. Functional effects were assessed by minigene splicing assays, quantitative PCR, dual-luciferase reporter assays, and a fly overexpression model.\n\nResults: Sequencing data variant analysis of 3 affected individuals identified a shared heterozygous deep-intronic RUNX1T1 variant (chr8:91994544G > A, hg38), subsequently verified in the five participating affected individuals. Although incorporated into a rare RUNX1T1 transcript, the variant did not affect splicing. Instead, it increased expression of canonical RUNX1T1 isoforms and enhanced reporter activity, consistent with a regulatory gain-of-function effect. RUNX1T1 ortholog (nvy) global overexpression in Drosophila resulted in morphological alterations of the feeding apparatus, including reduced rigidity and elongation of the labral sense organ.\n\nConclusion: In a kindred with apparently partially penetrant dominant non-syndromic EA, we identified a novel non-coding RUNX1T1 variant with functional evidence of a regulatory gain-of-function effect. These findings implicate RUNX1T1 dysregulation as a contributor to EA pathogenesis and highlight the importance of non-coding regulatory variation in congenital foregut malformations.",
  "abstract_shown": true,
  "affiliations": [
    "Morris Kahn Laboratory of Human Genetics, National Institute of Biotechnology in the Negev, Ben Gurion University, Be'er Sheva, Israel",
    "Faculty of Health Sciences, Ben Gurion University, Be'er Sheva, Israel",
    "Pediatric Gastroenterology Unit, Saban Children's Hospital, Soroka Medical Center, Be'er Sheva, Israel",
    "Genetics Institute, Soroka Medical Center, Be'er Sheva, Israel",
    "Department of Pediatric Surgery, Soroka Medical Center, Be'er Sheva, Israel",
    "Department of Life Sciences, Ben-Gurion University, Be'er Sheva, Israel",
    "Danek Gertner Institute of Human Genetics, Sheba Medical Center, Ramat-Gan, Israel"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 18,
  "authors": [
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      "name": "Nadav Agam"
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      "name": "Sarit Aharoni"
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      "name": "Baruch Yerushalmi"
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      "name": "Galina Ling"
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      "name": "Elad Brav"
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      "name": "Katya Oustinov"
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      "name": "Vadim Dolgin"
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      "name": "Ofek Freund"
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    {
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      "name": "Amit Safran"
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      "name": "Matan M. Jean"
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      "name": "Tomer Poleg"
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      "name": "Nitza Newman"
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    {
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      "name": "Zaki Assi"
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      "name": "Assaf Ben Zvi"
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      "name": "Ramon Y. Birnbaum"
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      "name": "Suad Sheikh-Suliman"
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    {
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      "name": "Uri Abdu"
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    {
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        0,
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        3,
        6
      ],
      "name": "Ohad S. Birk",
      "orcid": "0000-0003-1430-1296"
    }
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  "bibtex": "https://research.draconitic.com/paper/0z2rt2j4w0a9z.bib",
  "cited_by": 0,
  "doi": "10.1080/15476278.2026.2754587",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13733180/",
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  "issns": [
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    "1555-8592"
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  "landing_url": "https://doi.org/10.1080/15476278.2026.2754587",
  "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,
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      "2746|Esophageal and GI Pathology"
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  "pdf_url": "https://www.tandfonline.com/doi/pdf/10.1080/15476278.2026.2754587?needAccess=true",
  "pmcid": "PMC13733180",
  "pmid": "42961292",
  "published": "2026-10-30",
  "publisher": "Taylor & Francis",
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  "subjects": [
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  "title": "Functional characterization of a non-coding RUNX1T1 variant in a kindred with esophageal atresia",
  "title_text": "Functional characterization of a non-coding RUNX1T1 variant in a kindred with esophageal atresia",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:23:01Z",
  "url": "https://research.draconitic.com/paper/0z2rt2j4w0a9z",
  "venue": "Organogenesis",
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