title: Lethal neonatal rigidity and multifocal seizure syndrome--report of another family with a BRAT1 mutation.
abstract: We describe two siblings born to consanguineous Arab-Muslim parents who presented in early infancy with myoclonic seizures, hypertonia and contractures, arrested head growth, inability to swallow, and bouts of apnea-bradycardia, culminating in cardiac arrest and death. Whole-genome sequencing yielded a c.1173delG mutation in the BRAT1 gene. Three recent reports identified mutations in the same gene in three infants from three Amish sibships, one Mexican neonate and two Japanese siblings with similar clinical manifestations. The authors speculated that the destabilization of the encoded protein may underlie the catastrophic epilepsy and corticobasal neuronal degeneration. We suggest that BRAT1 be added to the growing list of genes that are related to severe early infantile (neonatal) epileptic encephalopathy.
authors.affiliation: Neurgenetics Clinic, Department of Child Neurology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: rachels2@clalit.org.il.
authors.forename: Rachel
authors.initials: R
authors.lastname: Straussberg
authors.affiliation: Neurgenetics Clinic, Department of Child Neurology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
authors.forename: Esther
authors.initials: E
authors.lastname: Ganelin-Cohen
authors.affiliation: Neurgenetics Clinic, Department of Child Neurology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Hadassah
authors.initials: H
authors.lastname: Goldberg-Stern
authors.affiliation: Molecular Medicine Laboratory, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Tzur
authors.affiliation: Raphael Recanati Genetics Institute, Rabin Medical Center, Petach Tikva, Israel; Molecular Medicine Laboratory, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Doron M
authors.initials: DM
authors.lastname: Behar
authors.affiliation: Felsenstein Medical Research Center, Petach Tikva, Israel; Genomic Bioinformatics Laboratory, Department of Molecular Biology, Ariel University, Ariel, Israel.
authors.forename: Pola
authors.initials: P
authors.lastname: Smirin-Yosef
authors.affiliation: Genomic Bioinformatics Laboratory, Department of Molecular Biology, Ariel University, Ariel, Israel.
authors.forename: Mali
authors.initials: M
authors.lastname: Salmon-Divon
authors.affiliation: Genetics Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Raphael Recanati Genetics Institute, Rabin Medical Center, Petach Tikva, Israel; Felsenstein Medical Research Center, Petach Tikva, Israel.
authors.forename: Lina
authors.initials: L
authors.lastname: Basel-Vanagaite
mesh_terms: D001049:Apnea / Q000209:etiology; D018912:Arabs; D001919:Bradycardia / Q000209:etiology; D003241:Consanguinity; D003679:Deglutition; D005190:Family; D017809:Fatal Outcome; D006323:Heart Arrest / Q000209:etiology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009127:Muscle Rigidity / Q000503:physiopathology*; D009154:Mutation / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D012640:Seizures / Q000503:physiopathology*; D013577:Syndrome
chemical_list: C573230:BRAT1 protein, human; D009687:Nuclear Proteins
keywords: Apnea; Bradycardia; Epilepsy; Hypertonicity; Infancy; Seizures