Clinical features of genetic Creutzfeldt-Jakob disease with V180I mutation in the prion protein gene.
OBJECTIVE
Genetic Creutzfeldt-Jakob disease (CJD) due to V180I mutation in the prion protein gene (PRNP) is of great interest because of the differences from sporadic CJD and other genetic prion diseases in terms of clinical features, as well as pathological and biochemical findings. However, few systematic observations about the clinical features in patients with this unique mutation have been published. Therefore, the goal of this study was to relate this mutation to other forms of CJD from a clinical perspective.


METHODS
We analysed clinical symptoms, prion protein genetics, biomarkers in cerebrospinal fluid (CSF) and MRI of patients.


METHODS
186 Japanese patients with the V180I mutation in PRNP.


RESULTS
Our results indicate that the V180I mutation caused CJD at an older age, with a slower progression and a lower possibility of developing myoclonus, cerebellar, pyramidal signs and visual disturbance compared with classical sporadic CJD with methionine homozygosity at codon 129 of PRNP. Cognitive impairment was the major symptom. Diffuse hyperintensity of the cerebral cortex in diffusion-weighted MRI might be helpful for diagnosis. Owing to the low positivity of PrP(Sc) in the CSF, genetic analysis was often required for a differential diagnosis from slowly progressive dementia.


CONCLUSIONS
We conclude that the V180I mutation in PRNP produces a late-developing and slow-developing, less severe form of CJD, whose lesions are uniquely distributed compared with sporadic and other genetic forms of CJD.
Department of Neurology and Neurological Science, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan.
Temu
T
Qina
Department of Neurology and Neurological Science, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan.
Nobuo
N
Sanjo
Department of Neurology and Neurological Science, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan.
Masaki
M
Hizume
Department of Neurology and Neurological Science, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan.
Maya
M
Higuma
Faculty of Medicine, Clinical Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
Makoto
M
Tomita
Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Ryuichiro
R
Atarashi
Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Katsuya
K
Satoh
Department of Neurology, National Hospital Organization Iou Hospital, Kanazawa, Japan.
Ichiro
I
Nozaki
Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
Tsuyoshi
T
Hamaguchi
Department of Public Health, Jichi Medical University, Tochigi, Japan.
Yosikazu
Y
Nakamura
Division of CJD Science and Technology, Department of Prion Protein Research, Tohoku University Graduate School of Medicine, Miyagi, Japan.
Atsushi
A
Kobayashi
Division of CJD Science and Technology, Department of Prion Protein Research, Tohoku University Graduate School of Medicine, Miyagi, Japan.
Tetsuyuki
T
Kitamoto
Department of Neurology and Neuropathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
Shigeo
S
Murayama
Department of Neurology, Neurological Institute, Kyushu University Graduate School of Medicine, Fukuoka, Japan.
Hiroyuki
H
Murai
Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
Masahito
M
Yamada
Department of Neurology and Neurological Science, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan.
Hidehiro
H
Mizusawa
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*; D012189:Retrospective Studies
C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions