{
  "abstract": "Developmental epileptic encephalopathy (DEE) comprises neurodevelopmental disorders with early-onset seizures and developmental impairment. Despite >900 implicated genes, many patients remain undiagnosed after short-read sequencing (SRS). We assessed long-read genome sequencing (LR-GS) in 38 previously unsolved infantile-onset DEE probands (10 singletons, 28 trios). Variant detection included single nucleotide variants (SNVs), structural variants, copy number variants and short tandem repeats in established repeat expansion disease genes. LR-GS identified candidate variants in 8 out of 38 probands (21%) missed by SRS: five large deletions, one SNV in a low-mappability region of NSF, one case resolved via haplotype phasing of compound heterozygous SNVs without parental samples and one case where LR-GS detected an allele missed due to coverage gaps. An additional eight probands (21%) harboured variants technically detectable by SRS but were missed due to newly associated genes, synonymous variants lacking splicing evaluation or prior analytic pipelines. LR-GS substantially increases diagnostic yield in unsolved infantile-onset DEE, supporting its incorporation into clinical workflows as a second-tier genetic test for otherwise unsolved neurodevelopmental disorders.",
  "authors": [
    {
      "affiliations": [
        "Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand",
        "Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand"
      ],
      "name": "Chanatjit Cheawsamoot"
    },
    {
      "affiliations": [
        "Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand",
        "Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand"
      ],
      "name": "Rungroj Thangpong"
    },
    {
      "affiliations": [
        "Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand",
        "Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand"
      ],
      "name": "Wanna Chetruengchai"
    },
    {
      "affiliations": [
        "Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand",
        "Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand"
      ],
      "name": "Songphon Kanlayaprasit"
    },
    {
      "affiliations": [
        "Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand",
        "Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand"
      ],
      "name": "Wuttichart Kamolvisit"
    },
    {
      "affiliations": [
        "Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand",
        "Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand"
      ],
      "name": "Phawin Kor-Anantakul"
    },
    {
      "affiliations": [
        "Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand",
        "Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand"
      ],
      "name": "Adjima Assawapitaksakul"
    },
    {
      "affiliations": [
        "Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand",
        "Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand"
      ],
      "name": "Ponghatai Boonsimma"
    },
    {
      "affiliations": [
        "Division of Pediatric Neurology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand"
      ],
      "name": "Sathida Poonmaksatit"
    },
    {
      "affiliations": [
        "Division of Pediatric Neurology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand"
      ],
      "name": "Krisnachai Chomtho"
    },
    {
      "affiliations": [
        "Division of Pediatric Neurology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand"
      ],
      "name": "Tayard Desudchit"
    },
    {
      "affiliations": [
        "Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand",
        "Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand"
      ],
      "name": "Vorasuk Shotelersuk"
    }
  ],
  "title": "Long-read genome sequencing increases diagnostic yield in a short-read sequencing unsolved developmental epileptic encephalopathy (DEE) cohort",
  "uid": "7d77861f-d24a-5c8a-bc01-953a41f450d7"
}