Clinical features of genetic Creutzfeldt-Jakob disease with V180I mutation in the prion protein gene

Temu Qina, Nobuo Sanjo, Masaki Hizume, Maya Higuma, Makoto Tomita, Ryuichiro Atarashi, Katsuya Satoh, Ichiro Nozaki, Tsuyoshi Hamaguchi, Yosikazu Nakamura, Atsushi Kobayashi, Tetsuyuki Kitamoto, Shigeo Murayama, Hiroyuki Murai, Masahito Yamada, Hidehiro Mizusawa

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39 Citations (Scopus)


Objectives: 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. Design: We analysed clinical symptoms, prion protein genetics, biomarkers in cerebrospinal fluid (CSF) and MRI of patients. Participants: 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 PrPSc 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.

Original languageEnglish
Article numbere004968
JournalBMJ open
Issue number5
Publication statusPublished - 2014

All Science Journal Classification (ASJC) codes

  • Medicine(all)


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