{
  "abstract": "Background Optical genome mapping (OGM) is a novel technology that enables high-resolution detection of structural variants. This study aimed to evaluate the diagnostic contribution of OGM in early-onset developmental epileptic encephalopathies (DEEs) with unresolved genetic causes.Materials and methods A total of 38 children with early-onset DEEs (aged 0–18 years) who remained undiagnosed despite conventional karyotyping, chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) were included. All patients underwent detailed phenotypic reassessment and WES reanalysis. One patient received a definitive molecular diagnosis following WES reanalysis. Four patients subsequently withdrew consent, and one patient was excluded due to inadequate DNA quality for OGM. OGM was therefore performed in the remaining 32 patients. Potential OGM findings were validated using appropriate laboratory techniques.Results Among the 32 patients who underwent OGM, three candidate structural variants were identified. Two variants (2/32, 6.3%), ogm[GRCh38] ins(X;?)(q27.3;?) and ogm[GRCh38] 6p24.1 (13083829_13279761)x1, were confirmed using orthogonal validation methods, resulting in the molecular diagnoses of Fragile X syndrome and PHACTR1-related DEE, respectively.Conclusion OGM contributed to the identification of clinically relevant structural variants in genetically undiagnosed early-onset DEEs. These findings support the complementary role of OGM in the genetic evaluation of complex neurodevelopmental disorders.",
  "authors": [
    {
      "affiliations": [
        "Department of Pediatrics, Division of Pediatric Neurology, Ege Universitesi Tip Fakultesi, Izmir, Turkey"
      ],
      "name": "Sanem Yilmaz"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Division of Pediatric Genetics, Ege Üniversitesi Tıp Fakültesi, Izmir, Turkey"
      ],
      "name": "Enise Avci Durmusalioglu"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Division of Pediatric Neurology, Ege Universitesi Tip Fakultesi, Izmir, Turkey"
      ],
      "name": "Dilara Ece Toprak Dogan"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Division of Pediatric Neurology, Ege Universitesi Tip Fakultesi, Izmir, Turkey"
      ],
      "name": "Seda Kanmaz"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Division of Pediatric Genetics, Ege Üniversitesi Tıp Fakültesi, Izmir, Turkey"
      ],
      "name": "Tahir Atik"
    },
    {
      "affiliations": [
        "Detagen Genetic Diseases Evaluation Center, Detagen, Kayseri, Turkey"
      ],
      "name": "Mehmet Burak Mutlu"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Division of Child Neurology, School of Medicine, Dokuz Eylul Universitesi, Alsancak, Turkey"
      ],
      "name": "Uluç Yiş"
    },
    {
      "affiliations": [
        "Dr Behçet Uz Child Disease and Pediatric Surgery Training and Research Hospital, University of Health Sciences, Istanbul, Turkey"
      ],
      "name": "Unsal Yilmaz"
    },
    {
      "affiliations": [
        "Dr Behçet Uz Child Disease and Pediatric Surgery Training and Research Hospital, University of Health Sciences, Istanbul, Turkey"
      ],
      "name": "Aycan Unalp"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Division of Pediatric Neurology, Ege Universitesi Tip Fakultesi, Izmir, Turkey"
      ],
      "name": "Sarenur Gökben"
    },
    {
      "affiliations": [
        "Intergen Genetics and Rare Diseases Diagnosis Research and Application Center, Intergen, Ankara, Turkey"
      ],
      "name": "Hasan Baş"
    },
    {
      "affiliations": [
        "Department of Medical Biology, Ege University, Izmir, Turkey"
      ],
      "name": "Arman Rostamlou"
    },
    {
      "affiliations": [
        "Department of Medical Biology, Ege University, Izmir, Turkey"
      ],
      "name": "Nur Selvi Gunel"
    },
    {
      "affiliations": [
        "Department of Medical Biology, Ege University, Izmir, Turkey"
      ],
      "name": "Cumhur Gunduz"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Division of Pediatric Neurology, Ege Universitesi Tip Fakultesi, Izmir, Turkey"
      ],
      "name": "Hasan Tekgul"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Division of Pediatric Genetics, Ege Üniversitesi Tıp Fakültesi, Izmir, Turkey"
      ],
      "name": "Esra Isik"
    }
  ],
  "title": "Optical genome mapping identifies previously undetected causal variants in early-onset developmental epileptic encephalopathies",
  "uid": "1fb4c33d-e75a-5c5f-885d-4fbf8f3542ab"
}