title: Mutations in the genes encoding eukaryotic translation initiation factor 2B in Japanese patients with vanishing white matter disease.
abstract: OBJECTIVE
  Vanishing white matter disease (VWM) is a chronic, progressive leukoencephalopathy associated with episodes of rapid deterioration following minor stress events such as head traumas or infectious disorders. The white matter of the patients with VWM exhibits characteristic radiological findings.
  
  
  METHODS
  The genes encoding all five subunits of eukaryotic translation initiation factor 2B (EIF2B) were analyzed in patients, who were tentatively diagnosed with VWM, by Sanger sequencing.
  
  
  RESULTS
  Seven mutations were identified in the genes encoding the subunits 1, 2, 4, and 5 of EIF2B. Among them, one mutation (p.V83E) in the subunit 2 (EIF2B2) was recurrently identified in three alleles, indicating the most common mutation in Japanese patients with VWM. Two patients were homozygous, and the other four patients were compound heterozygous.
  
  
  CONCLUSIONS
  All patients showed white matter abnormalities with various degrees. One patient showed manifestations of end-stage VWM disease. Some patients showed late onset and slow progression associated with brain magnetic resonance imaging displaying T2 high intensity only in the deep white matter. There was clinical heterogeneity among patients with VWM.
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan; Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Shino
authors.initials: S
authors.lastname: Shimada
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: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan; Department of Oral and Maxillofacial Surgery, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Sangu
authors.affiliation: Department of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, Fuchu, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Hoshino
authors.affiliation: Department of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, Fuchu, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hachiya
authors.affiliation: Department of Pediatrics, Tsukuba University, Tsukuba, Japan.
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Ohto
authors.affiliation: Department of Neurology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Hashi
authors.affiliation: Department of Neurology, National Hospital Organization Hyogo-Chuo National Hospital, Sanda, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nishida
authors.affiliation: Department of Neurology, National Hospital Organization Hyogo-Chuo National Hospital, Sanda, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Mitani
authors.affiliation: Department of Pediatrics, Okinawa Chubu Hospital, Uruma, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Kinjo
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Morimoto
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
mesh_terms: D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D020717:Eukaryotic Initiation Factor-2B / Q000097:blood / Q000235:genetics*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007564:Japan; D056784:Leukoencephalopathies / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010442:Peptide Chain Initiation, Translational; D055815:Young Adult
chemical_list: D020717:Eukaryotic Initiation Factor-2B
keywords: Eukaryotic translation initiation factor 2B (EIF2B); Leukoencephalopathy; Mutation; Vanishing white matter disease (VWM)