Prospective cohort study for identification of underlying genetic causes in neonatal encephalopathy using whole-exome sequencing

Theodora U.J. Bruun, Caro Lyne Desroches, Diane Wilson, Vann Chau, Tadashi Nakagawa, Masahiro Yamasaki, Shinya Hasegawa, Toshiyuki Fukao, Christian Marshall, Saadet Mercimek-Andrews

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


PurposeNeonatal encephalopathy, which is characterized by a decreased level of consciousness, occurs in 1-7/1,000 live-Term births. In more than half of term newborns, there is no identifiable etiological factor. To identify underlying genetic defects, we applied whole-exome sequencing (WES) in term newborns with neonatal encephalopathy as a prospective cohort study.MethodsTerm newborns with neonatal encephalopathy and no history of perinatal asphyxia were included. WES was performed using patient and both parents' DNA.ResultsNineteen patients fulfilling inclusion criteria were enrolled. Five patients were excluded owing to withdrawal of consent, no parental DNA samples, or a genetic diagnosis prior to WES. Fourteen patients underwent WES. We confirmed a genetic diagnosis in five patients (36%): epileptic encephalopathy associated with autosomal dominant de novo variants in SCN2A (p.Met1545Val), KCNQ2 (p.Asp212Tyr), and GNAO1 (p.Gly40Arg); lipoic acid synthetase deficiency due to compound heterozygous variants in LIAS (p.Ala253Pro and p.His236Gln); and encephalopathy associated with an X-linked variant in CUL4B (p.Asn211Ser).ConclusionWES is helpful at arriving genetic diagnoses in neonatal encephalopathy and/or seizures and brain damage. It will increase our understanding and probably enable us to develop targeted neuroprotective treatment strategies.

Original languageEnglish
Pages (from-to)486-494
Number of pages9
JournalGenetics in Medicine
Issue number5
Publication statusPublished - 2018 Apr 1


  • genetic
  • hypoxic-ischemic encephalopathy
  • neonatal encephalopathy
  • neonatal seizures
  • whole-exome sequencing

ASJC Scopus subject areas

  • Genetics(clinical)


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