{
  "abstract": "CHD2-related neurodevelopmental disorders are increasingly recognized as a distinct group of epileptic encephalopathies with heterogeneous clinical manifestations. Here, we report a 12-year-old female patient with pharmacoresistant epilepsy, mild cognitive impairment (IQ = 56), and extraneurological features including grade II kyphoscoliosis and planovalgus foot deformity. Video-EEG monitoring revealed a phenotype consistent with Jeavons syndrome, characterized by daily eyelid myoclonia with absences and marked photosensitivity with an eye closure sensitivity (ECS) phenomenon. Molecular genetic testing via whole-exome and Sanger sequencing identified two novel variants in the CHD2 gene (NM_001271.4): c.1634T>G (p.Leu545Arg) and c.3810G>C (p.Leu1270Phe). Long-read nanopore sequencing confirmed their de novo status and cis-positioning on the paternal allele. Structural bioinformatic analysis using AlphaFold3, FoldX/mCSM (v5.0 package), UCSF ChimeraX (v1.10.1), and PyMOL (v3.1.8) demonstrated that both variants individually destabilize the CHD2 protein, with a cumulative destabilizing effect when combined: p.Leu545Arg affects the ATP-binding domain, whereas p.Leu1270Phe disrupts hydrophobic packing within the C-terminal DNA-binding domain. These findings suggest accelerated protein degradation as a potential disease mechanism. Our data support the pathogenicity of these heterozygous cis-variants and implicate CHD2 haploinsufficiency as the leading etiopathogenic mechanism, though distinct domain-specific effects of each substitution may also contribute to the complex molecular synergy observed in this case.",
  "abstract_shown": true,
  "affiliations": [
    "Research Institute of Medical Genetics, Tomsk National Research Medical Center, Tomsk 634009, Russia",
    "Department of Medical Genetics, Siberian State Medical University, Tomsk 634050, Russia"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Andrew S. Zuev",
      "orcid": "0000-0001-9474-9335"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Elizaveta A. Fonova",
      "orcid": "0000-0002-1338-5451"
    },
    {
      "affs": [
        0
      ],
      "name": "Daria S. Kuznetsova",
      "orcid": "0009-0001-7792-7491"
    },
    {
      "affs": [
        0
      ],
      "name": "Vadim A. Stepanov",
      "orcid": "0000-0002-5166-331X"
    },
    {
      "affs": [
        0
      ],
      "name": "Nikolay A. Skryabin",
      "orcid": "0000-0002-2491-3141"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/91z45189spjgx.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27209120",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705119/?tool=EBI",
  "id": "91z45189spjgx",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/20/9120",
  "language": "eng",
  "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": [
    [
      "openalex",
      "2738|Epilepsy research and treatment"
    ]
  ],
  "openalex": "W7221806948",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705119/pdf/?tool=EBI",
  "pmcid": "PMC13705119",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/91z45189spjgx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:55Z",
      "native_id": "10.3390/ijms27209120",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/20/9120"
    },
    {
      "first_seen": "2026-10-30T12:21:31Z",
      "native_id": "PMC:PMC13705119",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13705119"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2738|Epilepsy research and treatment",
      "subfield": "psychiatry"
    }
  ],
  "title": "Novel Genetic Variants of the CHD2 Gene in cis Position in a Patient with Epileptic Encephalopathy: A Case Report and In Silico Analysis of the Impact of the Variants on the Protein",
  "title_text": "Novel Genetic Variants of the CHD2 Gene in cis Position in a Patient with Epileptic Encephalopathy: A Case Report and In Silico Analysis of the Impact of the Variants on the Protein",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:31Z",
  "url": "https://research.draconitic.com/paper/91z45189spjgx",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}