Postmortem Whole Exome Sequencing Identifies Novel EIF2B3 Mutation With Prenatal Phenotype in 2 Siblings.
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.
['Song|Hannah|H|', 'Haeri|Sina|S|', 'Vogel|Hannes|H|', 'van der Knaap|Marjo|M|', 'Van Haren|Keith|K|']
D001921:Brain D020717:Eukaryotic Initiation Factor-2B D017809:Fatal Outcome D006801:Humans D007223:Infant D056784:Leukoencephalopathies D008297:Male D009154:Mutation D010641:Phenotype D035781:Siblings D000073359:Whole Exome Sequencing
prenatal vanishing white matter disease infant leukodystrophy leukoencephalopathy