Postmortem Whole Exome Sequencing Identifies Novel EIF2B3 Mutation with Prenatal Phenotype in 2 Siblings

Hannah Song, Sina Haeri, Hannes Vogel, Marjo Van Der Knaap, Keith Van Haren

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6 Citations (Scopus)


Objective: We describe 2 male siblings with a severe, prenatal phenotype of vanishing white matter disease and the impact of whole exome sequencing on their diagnosis and clinical care. Methods: The 2 children underwent detailed clinical characterization, through clinical and laboratory testing, as well as prenatal and postnatal imaging. Biobanked blood from the 2 siblings was submitted for whole exome sequencing at Baylor Laboratories. Results: Both male children had abnormal prenatal neuroimaging and suffered precipitous, fatal neurologic decline. Neuropathologic findings included subependymal pseudocysts, microcalcifications, and profound lack of brain myelin and sparing of peripheral nerve myelin. A novel homozygous mutation in the EIF2B3 gene (c.97A>G [p.Lys33Glu]) was found in both children; both parents were heterozygous carriers. The family subsequently conceived a healthy child via in vitro fertilization with preimplantation mutation screening. Conclusion: These histories expand the prenatal phenotype of eIF2b-related disorders and poignantly illustrate the impact that unbiased genomic sequencing can have on the diagnosis and medical decision making for families affected by childhood neurodegenerative disorders.

Original languageEnglish
Pages (from-to)867-870
Number of pages4
JournalJournal of child neurology
Issue number10
Publication statusPublished - 1 Sept 2017


  • infant
  • leukodystrophy
  • leukoencephalopathy
  • prenatal
  • vanishing white matter disease

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