Two different clinical phenotypes of Creutzfeldt-Jakob disease with a M232R substitution.
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.
Shiga
Yusei
Y
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
Satoh
Katsuya
K
Kitamoto
Tetsuyuki
T
Kanno
Sigenori
S
Nakashima
Ichiro
I
Sato
Shigeru
S
Fujihara
Kazuo
K
Takata
Hiroshi
H
Nobukuni
Keigo
K
Kuroda
Shigetoshi
S
Takano
Hiroki
H
Umeda
Yoshitaka
Y
Konno
Hidehiko
H
Nagasato
Kunihiko
K
Satoh
Akira
A
Matsuda
Yoshito
Y
Hidaka
Mitsuru
M
Takahashi
Hirokatsu
H
Sano
Yasuteru
Y
Kim
Kang
K
Konishi
Takashi
T
Doh-ura
Katsumi
K
Sato
Takeshi
T
Sasaki
Kensuke
K
Nakamura
Yoshikazu
Y
Yamada
Masahito
M
Mizusawa
Hidehiro
H
Itoyama
Yasuo
Y
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
D048948:14-3-3 Proteins; D011328:Prions; D001120:Arginine; D008715:Methionine