title: Loss-of-function mutations of STXBP1 in patients with epileptic encephalopathy.
abstract: Epileptic encephalopathy, which commences during early infancy, is a severe epileptic syndrome that manifests as age-dependent seizures and severe developmental delay. The syntaxin-binding protein 1 gene (STXBP1) is one of the genes responsible for epileptic encephalopathy. We conducted a cohort study to analyze STXBP1 in 42 patients with epileptic encephalopathy. We identified four novel mutations: two splicing mutations, a frameshift mutation, and a nonsense mutation. All of these mutations were predicted to cause loss-of-function. This result suggests loss-of-function is a common mechanism underlying STXBP1-related epileptic encephalopathy. The four patients showed epileptic features consistent with STXBP1-related epileptic encephalopathy, but showed variable radiological findings, including brain volume loss and myelination delay.
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan. Electronic address: yamamoto.toshiyuki@twmu.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimojima
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Akita University, Akita, Japan.
authors.forename: Tamami
authors.initials: T
authors.lastname: Yano
authors.affiliation: National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
authors.forename: Rumiko
authors.initials: R
authors.lastname: Takayama
authors.affiliation: National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ikeda
authors.affiliation: National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imai
mesh_terms: D001921:Brain / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D015331:Cohort Studies; D004569:Electroencephalography; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007223:Infant; D008297:Male; D051938:Munc18 Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D012326:RNA Splicing; D013036:Spasms, Infantile / Q000235:genetics* / Q000378:metabolism
chemical_list: D018389:Codon, Nonsense; D051938:Munc18 Proteins; C497937:STXBP1 protein, human
keywords: Loss-of-function; Ohtahara syndrome; STXBP1-related epileptic encephalopathy; West syndrome