{
  "abstract": "KAT6A syndrome is a complex neurodevelopmental disorder caused by heterozygous pathogenic KAT6A variants inflicting variable degrees of developmental delay and intellectual disability via a mechanism that remains largely uncharacterized. To further our understanding, we differentiated KAT6A syndrome patient-derived induced pluripotent stem cells into neural progenitor cells and cortical neurons. KAT6A syndrome patient-derived cells exhibit an altered transcriptome, with many of the dysregulated genes associated with autism spectrum disorder. At an early stage of differentiation, KAT6A-mutant cortical neurons show many elevated neurodevelopment-specific genes, including key transcription factors. Detailed electrophysiological measurements uncover that KAT6A-mutant cortical neurons display a hyperexcitability phenotype at an early stage of differentiation, followed by hypoexcitability at a later stage, compared with control neurons. These electrophysiological alterations were accompanied by decreased sodium and potassium currents. Remarkably, early KAT6A-mutant neurons exhibit a markedly lower percentage of GABA-positive neurons and increased spontaneous calcium activity as compared with control neurons. Moreover, multiple morphometric alterations in early-stage KAT6A-mutant cortical neurons indicate premature maturation, including increased neurite outgrowth, arbor complexity and soma size. Consistently, KAT6A knockout SH-SY5Y cells exhibit impaired differentiation capability and dysregulated gene expression. These novel findings establish the deleterious impact of pathogenic KAT6A variants on cortical neuron differentiation and electrophysiological function.",
  "abstract_shown": true,
  "affiliations": [
    "The Fred Wyszkowski Cancer Research Laboratory, Faculty of Biology, Technion-Israel Institute of Technology, Haifa 3200003, Israel.",
    "Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel.",
    "The Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.",
    "The Regenerative Medicine and Stem Cell (RMSC) Research Center. Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.",
    "The Zelman Center of Neuroscience, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.",
    "Genetic Institute, Rambam Health Care Campus, Haifa 3109601, Israel.",
    "Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 3109601, Israel."
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Naama Wiesel-Motiuk"
    },
    {
      "affs": [
        1
      ],
      "name": "Ashwani Choudhary"
    },
    {
      "affs": [
        1
      ],
      "name": "Yara Hussein"
    },
    {
      "affs": [
        1
      ],
      "name": "Utkarsh Tripathi"
    },
    {
      "affs": [
        1
      ],
      "name": "Wote Amelo Rike"
    },
    {
      "affs": [
        1
      ],
      "name": "Aviram Shemen"
    },
    {
      "affs": [
        1
      ],
      "name": "Ritu Nayak"
    },
    {
      "affs": [
        1
      ],
      "name": "Souvik Chakraborty"
    },
    {
      "affs": [
        1
      ],
      "name": "Omveer Sharma"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Tatiana Rabinski"
    },
    {
      "affs": [
        0
      ],
      "name": "Michal Stark"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Karin Weiss"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Gad D Vatine"
    },
    {
      "affs": [
        1
      ],
      "name": "Shani Stern"
    },
    {
      "affs": [
        0
      ],
      "name": "Yehuda G Assaraf"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/08j0b39j4x7hw.bib",
  "cited_by": 0,
  "doi": "10.7150/ijbs.134210",
  "fulltext_url": "https://europepmc.org/articles/PMC13685762",
  "id": "08j0b39j4x7hw",
  "issns": [
    "1449-2288"
  ],
  "landing_url": "https://europepmc.org/article/MED/42909968",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1311|Genetics and Neurodevelopmental Disorders"
    ]
  ],
  "openalex": "W7214637904",
  "pdf_url": "https://europepmc.org/articles/PMC13685762?pdf=render",
  "pmcid": "PMC13685762",
  "pmid": "42909968",
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/08j0b39j4x7hw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:14Z",
      "native_id": "MED:42909968",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42909968"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Genetics and Neurodevelopmental Disorders",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "KAT6A-Mutant iPSC-Derived Cortical Neurons Display Precocious Maturation, Dysregulated Electrophysiology, and Altered Morphology.",
  "title_text": "KAT6A-Mutant iPSC-Derived Cortical Neurons Display Precocious Maturation, Dysregulated Electrophysiology, and Altered Morphology.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:14Z",
  "url": "https://research.draconitic.com/paper/08j0b39j4x7hw",
  "venue": "International journal of biological sciences",
  "versions": []
}