title: Two different clinical phenotypes of Creutzfeldt-Jakob disease with a M232R substitution.
abstract: OBJECTIVE
  To describe the clinical features of Creutzfeldt-Jakob disease with a substitution of arginine for methionine (M232R substitution) at codon 232 (CJD232) of the prion protein gene (PRNP).
  
  
  METHODS
  We evaluated the clinical and laboratory features of 20 CJD232 patients: age of onset, initial symptoms, duration until becoming akinetic and mute, duration until occurrence of periodic sharp and wave complexes on EEG (PSWC), MRI findings, and the presence of CSF 14-3-3 protein. Immunohistochemically, prion protein (PrP) deposition was studied.
  
  
  RESULTS
  None of the patients had a family history of CJD. We recognized two clinical phenotypes: a rapidly progressive type (rapidtype) and a slowly progressive type (slow-type). Out of 20 patients, 15 became akinetic and mute, demonstrated myoclonus, and showed PSWC within a mean duration of 3.1, 2.4, and 2.8 months, respectively (rapid-type). Five showed slowly progressive clinical courses (slow-type). Five became akinetic and mute and four demonstrated myoclonus within a mean duration of 20.6 and 15.3 months, respectively, which were significantly longer than those in the rapid-type. Only one demonstrated PSWC 13 months after the onset. Diffuse synaptic-type deposition was demonstrated in four rapidtype patients, and perivacuolar and diffuse synaptic-type deposition in two, and diffuse synaptic-type deposition in one slow-type patient. Three of 50 suspected but non-CJD patients had the M232R substitution.
  
  
  CONCLUSIONS
  Patients with CJD232 had no family history like patients with sCJD, and showed two different clinical phenotypes in spite of having the same PRNP genotype. More studies are needed to determine whether M232R substitution causes the disease and influences the disease progression.
authors.affiliation: Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. yshiga@em.neurol.med.tohoku.ac.jp
authors.forename: Yusei
authors.initials: Y
authors.lastname: Shiga
authors.forename: Katsuya
authors.initials: K
authors.lastname: Satoh
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Kitamoto
authors.forename: Sigenori
authors.initials: S
authors.lastname: Kanno
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakashima
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sato
authors.forename: Kazuo
authors.initials: K
authors.lastname: Fujihara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takata
authors.forename: Keigo
authors.initials: K
authors.lastname: Nobukuni
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Kuroda
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takano
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Umeda
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Konno
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Nagasato
authors.forename: Akira
authors.initials: A
authors.lastname: Satoh
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hidaka
authors.forename: Hirokatsu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Sano
authors.forename: Kang
authors.initials: K
authors.lastname: Kim
authors.forename: Takashi
authors.initials: T
authors.lastname: Konishi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Doh-ura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sato
authors.forename: Kensuke
authors.initials: K
authors.lastname: Sasaki
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Masahito
authors.initials: M
authors.lastname: Yamada
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Mizusawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Itoyama
mesh_terms: D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid; D000368:Aged; D001120:Arginine / Q000235:genetics*; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011328:Prions / Q000235:genetics* / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D011328:Prions; D001120:Arginine; D008715:Methionine