Relationships between Clinicopathological Features and Cerebrospinal Fluid Biomarkers in Japanese Patients with Genetic Prion Diseases

Higuma, Maya; Sanjo, Nobuo; Satoh, Katsuya; Shiga, Yusei; Sakai, Kenji; Nozaki, Ichiro; Hamaguchi, Tetsuya; Nakamura, Yosikazu; Kitamoto, Tetsuyuki; Shirabe, Susumu; Murayama, Shigeo; Yamada, Masahito; Tateishi, Jun; Mizusawa, Hidehiro

doi:10.1371/journal.pone.0060003

Cited by 38 publications

(98 citation statements)

References 32 publications

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“…In this cohort, western blotting of brain homogenates from patients with V180I indicated only weak bands of the monoglycosylated and unglycosylated fragments 5. In the future, studies should examine the role of factors that influence lesion topology on the disease's clinical expression and progression.…”

Section: Discussionmentioning

confidence: 79%

“…We evaluated 14-3-3 and total τ (t-τ) protein levels in the CSF by western blotting as previously described 5. PrP Sc in the CSF was detected by real-time quaking induced conversion (RT-QUIC), as previously described 12.…”

Section: Methodsmentioning

confidence: 99%

“…While the E200K mutation occurs most frequently in Europe,3 the V180I mutation is the most frequent mutation in Japan 5. Currently, several reports indicate that the V180I mutation in PRNP accounts for specific clinical and pathological findings 5–8.…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, patients with V180I show several specific clinical features different from those of sporadic Creutzfeldt-Jakob disease (sCJD) or other gPrDs 9. We have previously reviewed clinical symptoms and cerebrospinal fluid (CSF) markers of several PRNP mutations, including V180I 5. Patients with V180I are readily distinguishable from patients with other dementia because they show specific hyperintensity in the cerebral cortex in diffusion-weighted MRI.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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ObjectivesGenetic 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.DesignWe analysed clinical symptoms, prion protein genetics, biomarkers in cerebrospinal fluid (CSF) and MRI of patients.Participants186 Japanese patients with the V180I mutation in PRNP.ResultsOur 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.ConclusionsWe 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.

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Section: Discussionmentioning

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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“…Similarly, several neuropathological features that are associated with the V180I‐129M/PrP Sc type 2 combination, including the florid spongiform change lacking confluent vacuoles, as well as the faint synaptic type pattern of PrP immunostaining, do not fully match those of the sCJDMM2 subtypes .…”

Section: Phenotypic Spectrum and Classification Of Disease Subtypesmentioning

confidence: 98%

Recent advances in the histo‐molecular pathology of human prion disease

et al. 2019

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Prion diseases are progressive neurodegenerative disorders affecting humans and other mammalian species. The term prion, originally put forward to propose the concept that a protein could be infectious, refers to PrP Sc , a misfolded isoform of the cellular prion protein (PrP C ) that represents the pathogenetic hallmark of these disorders. The discovery that other proteins characterized by misfolding and seeded aggregation can spread from cell to cell, similarly to PrP Sc , has increased interest in prion diseases. Among neurodegenerative disorders, however, prion diseases distinguish themselves for the broader phenotypic spectrum, the fastest disease progression and the existence of infectious forms that can be transmitted through the exposure to diseased tissues via ingestion, injection or transplantation. The main clinicopathological phenotypes of human prion disease include Creutzfeldt-Jakob disease, by far the most common, fatal insomnia, variably protease-sensitive prionopathy, and Gerstmann-Sträussler-Scheinker disease. However, clinicopathological manifestations extend even beyond those predicted by this classification. Because of their transmissibility, the phenotypic diversity of prion diseases can also be propagated into syngenic hosts as prion strains with distinct characteristics, such as incubation period, pattern of PrP Sc distribution and regional severity of histopathological changes in the brain. Increasing evidence indicates that different PrP Sc conformers, forming distinct ordered aggregates, encipher the phenotypic variants related to prion strains. In this review, we summarize the most recent advances concerning the histo-molecular pathology of human prion disease focusing on the phenotypic spectrum of the disease including co-pathologies, the characterization of prion strains by experimental transmission and their correlation with the physicochemical properties of PrP Sc aggregates.

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Genetic prion disease: Experience of a rapidly progressive dementia center in the United States and a review of the literature

Takada

Kim

Cleveland

et al. 2016

American J of Med Genetics Pt B

101

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Although prion diseases are generally thought to present as rapidly progressive dementias with survival of only a few months, the phenotypic spectrum for genetic prion diseases (gPrDs) is much broader. The majority have a rapid decline with short survival, but many patients with gPrDs present as slowly progressive ataxic or parkinsonian disorders with progression over a few to several years. A few very rare mutations even present as neuropsychiatric disorders, sometimes with systemic symptoms such as gastrointestinal disorders and neuropathy, progressing over years to decades. gPrDs are caused by mutations in the prion protein gene (PRNP), and have been historically classified based on their clinicopathological features as genetic Jakob-Creutzfeldt disease (gJCD), Gerstmann-Sträussler-Scheinker (GSS), or Fatal Familial Insomnia (FFI). Mutations in PRNP can be missense, nonsense, and octapeptide repeat insertions or a deletion, and present with diverse clinical features, sensitivities of ancillary testing, and neuropathological findings. We present the UCSF gPrD cohort, including 129 symptomatic patients referred to and/or seen at UCSF between 2001 and 2016, and compare the clinical features of the gPrDs from 22 mutations identified in our cohort with data from the literature, as well as perform a literature review on most other mutations not represented in our cohort. E200K is the most common mutation worldwide, is associated with gJCD, and was the most common in the UCSF cohort. Among the GSS-associated mutations, P102L is the most commonly reported and was also the most common at UCSF. We also had several octapeptide repeat insertions (OPRI), a rare nonsense mutation (Q160X), and three novel mutations (K194E, E200G, and A224V) in our UCSF cohort. © 2016 Wiley Periodicals, Inc.

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Relationships between Clinicopathological Features and Cerebrospinal Fluid Biomarkers in Japanese Patients with Genetic Prion Diseases

Cited by 38 publications

References 32 publications

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

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

Recent advances in the histo‐molecular pathology of human prion disease

Genetic prion disease: Experience of a rapidly progressive dementia center in the United States and a review of the literature

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