title: Early-Onset Severe Encephalopathy with Epilepsy: The BRAT1 Gene Should Be Added to the List of Causes.
abstract: A variety of pathologies can underlie early-onset severe encephalopathy with epilepsy. To aid the diagnostic process in such patients we present an overview of causes, including the rapidly expanding list of genes involved. When no explanation is found, whole-exome sequencing (WES) can be used in an attempt to identify gene defects in patients suspected to suffer from a genetic form. We describe three siblings, born to consanguineous parents, with a lethal severe epileptic encephalopathy with early-infantile onset, including their magnetic resonance imaging, electroencephalography and, in one case, neuropathological findings. Using WES a homozygous frameshift mutation in the BRAT1 gene, c.638dup p.(Val214Glyfs*189), was identified. We present our cases in the context of all published cases with mutations in the BRAT1 gene and conclude that BRAT1 should be added to the growing list of genes related to early-onset severe encephalopathy with epilepsy.
authors.affiliation: Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Laura A
authors.initials: LA
authors.lastname: van de Pol
authors.affiliation: Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Nicole I
authors.initials: NI
authors.lastname: Wolf
authors.affiliation: Department of Neonatology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Mirjam M
authors.initials: MM
authors.lastname: van Weissenbruch
authors.affiliation: Department of Clinical Neurophysiology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Cornelie J
authors.initials: CJ
authors.lastname: Stam
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Janneke M
authors.initials: JM
authors.lastname: Weiss
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Quinten
authors.initials: Q
authors.lastname: Waisfisz
authors.affiliation: Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Sietske H
authors.initials: SH
authors.lastname: Kevelam
authors.affiliation: Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Mariana
authors.initials: M
authors.lastname: Bugiani
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jiddeke M
authors.initials: JM
authors.lastname: van de Kamp
authors.affiliation: Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marjo S
authors.initials: MS
authors.lastname: van der Knaap
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D001921:Brain / Q000473:pathology; D001927:Brain Diseases / Q000235:genetics*; D003241:Consanguinity; D004569:Electroencephalography; D004827:Epilepsy / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D012189:Retrospective Studies; D012720:Severity of Illness Index; D035781:Siblings
chemical_list: C573230:BRAT1 protein, human; D009687:Nuclear Proteins