Dataset Information

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

ABSTRACT:

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 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.

SUBMITTER: Qina T

PROVIDER: S-EPMC4025468 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Publications

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

Qina Temu T Sanjo Nobuo N Hizume Masaki M Higuma Maya M Tomita Makoto M Atarashi Ryuichiro R Satoh Katsuya K Nozaki Ichiro I Hamaguchi Tsuyoshi T Nakamura Yosikazu Y Kobayashi Atsushi A Kitamoto Tetsuyuki T Murayama Shigeo S Murai Hiroyuki H Yamada Masahito M Mizusawa Hidehiro H

BMJ open 20140516 5

<h4>Objectives</h4>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 CJ ...[more]

PMID: 24838726

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Project description:Genetic Creutzfeldt-Jakob disease (gCJD) with V180I prion protein gene (PRNP) mutation shows weaker prion protein (PrP) deposition histologically compared with sporadic CJD, and it is more difficult to detect protease-resistant prion protein in immunoblotting. However, we previously reported the autopsy case of a patient with V180I gCJD who was treated with pentosan polysulfate sodium (PPS); this case had increased protease-resistant PrP deposition. It has been suggested that PPS might reduce protease-resistant PrP; however, the detailed pharmacological and histopathological effects of PPS in humans remain unknown. We examined autopsied human brain tissue from four cases with V180I gCJD that were added to our archives between 2011 and 2021: two cases treated with PPS and two cases without PPS. We conducted a neuropathological assessment, including immunohistochemistry for PrP. We also performed immunoblotting for PrP on homogenate samples from each brain to detect protease-resistant PrP using both a conventional procedure and size-exclusion gel chromatography for the purification of oligomeric PrP. Both PPS-treated cases showed long survival time over 5 years from onset and increased PrP deposition with a characteristic pattern of coarse granular depositions and congophilic PrP microspheres, whereas the cases without PPS showed around 1-year survival from onset and relatively mild neuronal loss and synaptic PrP deposition. Although cortical gliosis seemed similar among all cases, aquaporin 4-expression as a hallmark of astrocytic function was increased predominantly in PPS cases. Immunoblotting of non-PPS cases revealed protease-resistant PrP in the oligomeric fraction only, whereas the PPS-treated cases showed clear signals using conventional procedures and in the oligomeric fraction. These unique biochemical and histopathological changes may reflect the progression of V180I gCJD and its modification by PPS, suggesting the possible existence of toxic PrP-oligomer in the pathophysiology of V180I gCJD and beneficial effects of PPS toward the aggregation and detoxication of toxic PrP-oligomer.

Dataset Information

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

Objectives

Design

Participants

Results

Conclusions

Publications

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

Similar Datasets

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