Proband-Only Clinical Exome Sequencing for Neurodevelopmental Disabilities

Se Hee Kim, Borahm Kim, Joon Soo Lee, Heung Dong Kim, Jong Rak Choi, Seung Tae Lee, Hoon Chul Kang

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Background: Whole exome sequencing on family trios gives the highest diagnostic yield, but high cost limits its application. Here, we performed proband-only clinical exome sequencing in a population of patients with neurodevelopmental disabilities and tested the diagnostic yield. Methods: This observational, retrospective study included 108 unrelated patients with neurodevelopmental disabilities who underwent clinical exome sequencing at the outpatient clinics of the Severance Children's Hospital, Seoul, South Korea, between March 2017 and May 2018. Clinical exome sequencing targeted 4503 disease-causing genes. Results: The overall diagnostic rate was 38.0% (41 of 108) when proband-only clinical exome sequencing was performed without additional parental testing. Four sequence variants were reclassified as likely pathogenic after parental testing, representing an additional 3.7% of the diagnostic yield. The final diagnostic rate was 41.7% (45 of 108). Of 45 patients with genetic abnormalities, a total of 38 sequence variations were detected in 33 (30.6%) patients with five homozygous cases, and 13 chromosomal copy number variants were detected in 12 (11.1%) patients. Novel variants of known causal genes for neurodevelopmental disabilities were detected in 18 (16.7%) patients. These were variants that could be reclassified as likely pathogenic if the de novo nature of the mutation was confirmed after testing of parental samples. Conclusions: Proband-only clinical exome sequencing is a practical diagnostic tool that may be implemented in the clinical setting for patients with neurodevelopmental disabilities. A cost-effective approach to neurodevelopmental disabilities would be a proband-only clinical exome sequencing followed by parental testing of selective candidate variants.

Original languageEnglish
Pages (from-to)47-54
Number of pages8
JournalPediatric Neurology
Publication statusPublished - 2019 Oct

Bibliographical note

Funding Information:
Funding source: This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HI18C0586).

Publisher Copyright:
© 2019 Elsevier Inc.

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Developmental Neuroscience
  • Clinical Neurology


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