Creutzfeldt-Jakob Disease with a Codon 210 Mutation: First Pathological Observation in a Japanese Patient

Tajima, Yasutaka; Satoh, Chika; Mito, Yasunori; Kitamoto, Tetsuyuki

doi:10.2169/internalmedicine.53.0916

Cited by 6 publications

(14 citation statements)

References 15 publications

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“…All three cases show acute onset and rapid progression in the first two months. Similar as other reported cases [ 13 , 20 ], The clinical features of three Chinese V210I gCJD are more like sCJD, with rapid progressive dementia and four other main neurological symptoms. Mental problems and ataxia are frequent initial disorders.…”

Section: Discussionsupporting

confidence: 88%

“…V210I gCJD is one of the commonest subtypes in European and American countries [ 8 , 9 , 10 , 11 , 12 ]. It has been also identified in Japan and Korea [ 13 , 14 , 15 ], however it is never described in Chinese, although more than 200 genetic prion diseases consisting of 16 different mutations were diagnosed via the Chinese National Surveillance for CJD in the past 15 years [ 3 , 16 ]. In 2019, three Chinese V210I gCJD cases were identified and diagnosed with rapid clinical progression.…”

Section: Introductionmentioning

confidence: 99%

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Clinical and Laboratory Features of Three Rare Chinese V210I gCJD Patients

et al. 2020

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Genetic human prion diseases are a group of inherited encephalopathies directly associated with different mutations in PrP-encoding gene PRNP, including more than 50 different mutations worldwide. Some genotypes of mutations show ethno-correlation, and among them, genetic Creutzfeldt–Jacob disease (gCJD) with V210I mutation is frequent in European countries but rare in East Asia. Here, we comparatively analyzed the clinical and laboratory features of three Chinese patients with V210I mutant identified via the Chinese National CJD Surveillance System (CNS-CJD) in 2019. Two cases were Han Chinese and one was Hui Chinese, without blood kinship. The onset ages of three cases were 69, 64, and 59 years old, respectively. The clinical features of V210I gCJD were similar to sporadic CJD (sCJD), displaying typical clinical symptoms and signs, except that Case 3 did not show myoclonic movement. All three cases displayed sCJD-associated abnormalities on MRI and positive CSF 14-3-3, while two cases recorded typical EEG abnormalities. Only one case was positive in CSF real-time quaking-induced conversion (RT-QuIC). Appearances of mutism in three cases were relatively fast, with the intervals of 30 to 50 days after onset. Family history was not reported in all three cases. Those V210I gCJD cases are rare in China, and probably the first three in East Asia.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Clinical and Laboratory Features of Three Rare Chinese V210I gCJD Patients

et al. 2020

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“…V210I is a pathogenic CJD mutation, described in Europe, Africa, 59 , 60 Korea, and Japan. 61 – 63 Frequency of mutation was around 16.2% in EuroCJD. The mutation was identified in the Heidenhain (visual impairment-associated) form of variant CJD (vCJD).…”

Section: Summary Of Prion Mutationsmentioning

confidence: 99%

“…The mutation was identified in the Heidenhain (visual impairment-associated) form of variant CJD (vCJD). 63 Similarly to V180I, V210I is located in the α2–α3 inter-helical interface of PrP, these two residues are located opposite to each other, and there is direct hydrophobic contact between them. 64 The mutation might induce the rearrangement of hydrophobic core, resulting in alternations in the β2–α2 interaction, and leading to spontaneous generation of PrP Sc .…”

Section: Summary Of Prion Mutationsmentioning

confidence: 99%

Characterization of mutations in <em>PRNP</em> (prion) gene and their possible roles in neurodegenerative diseases

Bagyinszky

Giau

Youn

et al. 2018

NDT

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Abnormal prion proteins are responsible for several fatal neurodegenerative diseases in humans and in animals, including Creutzfeldt–Jakob disease (CJD), Gerstmann–Sträussler–Scheinker disease, and fatal familial insomnia. Genetics is important in prion diseases, but in the most cases, cause of diseases remained unknown. Several mutations were found to be causative for prion disorders, and the effect of mutations may be heterogeneous. In addition, different prion mutations were suggested to play a possible role in additional phenotypes, such as Alzheimer’s type pathology, spongiform encephalopathy, or frontotemporal dementia. Pathogenic nature of several prion mutations remained unclear, such as M129V and E219K. These two polymorphic sites were suggested as either risk factors for different disorders, such as Alzheimer’s disease (AD), variant CJD, or protease-sensitive prionopathy, and they can also be disease-modifying factors. Pathological overlap may also be possible with AD or progressive dementia, and several patients with prion mutations were initially diagnosed with AD. This review also introduces briefly the diagnosis of prion diseases and the issues with their diagnosis. Since prion diseases have quite heterogeneous phenotypes, a complex analysis, a combination of genetic screening, cerebrospinal fluid biomarker analysis and imaging technologies could improve the early disease diagnosis.

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“…Missense variants in PRNP have been reported in patients with genetic prion disease. The c.628G>A (p.V210I) variant has been reported in many patients with prion disease (Bagyinszky, Giau, Youn, An, & Kim, ; Biljan et al., ; Furukawa., Kitamoto, Hashiguchi, & Tateishi, ; Imbriani et al, ; Mouillet‐Richard et al, ; Nozaki et al, ; Pocchiari et al, ; Ripoll et al, ; Shyu, Hsu, Kao, & Tsao, ; Tajima, Satoh, Mito, & Kitamoto, ). Mouse models inoculated with brain extracts from patients with the p.V210I variant developed symptoms of prion disease ~200 days postinoculation (Mastrianni et al, ).…”

Section: Case Reportmentioning

confidence: 99%

A case report of genetic prion disease with two different PRNP variants

Piazza

Prior

Khalsa

et al. 2020

Molec Gen & Gen Med

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Background Prion diseases are a group of lethal neurodegenerative conditions that occur when the normal, cellular form of the prion protein (PrPC) is converted into an abnormal, scrapie, form of the protein (PrPSc). Disease may be caused by genetic, infectious, or sporadic etiologies. The genetic form of prion disease comprises~10%–15% of all cases. Prion disease is typically inherited in an autosomal dominant manner. The low incidence of disease makes it highly unlikely that a patient would have two different pathogenic variants. However, we recently identified a case in which the patient did have two pathogenic PRNP variants and presented with an atypical phenotype. Methods The patient was evaluated at the Washington Hospital Healthcare System in Fremont, CA. The clinical information for this case report was obtained retrospectively. Variants in the PRNP were identified by polymerase chain reaction (PCR) amplification of exon two of the gene followed by bi‐directional sequence analysis. To determine the phase of the identified variants, a restriction enzyme digestion was utilized, followed by sequence analysis of the products. Cerebral spinal fluid (CSF) was analyzed for surrogate markers of prion disease, 14–3–3 and Tau proteins. CSF real‐time quaking‐induced conversion (RT‐QuIC) assays were also performed. Results The patient was a compound heterozygote for the well‐characterized c.628G>A (p.Val210Ile) variant and the rare octapeptide deletion of two repeats [c.202_249del48 (p.P68_Q83del)]. Clinically, the patient presented with an early onset demyelinating peripheral neuropathy, followed by later onset cognitive symptoms. Conclusion This presentation is reminiscent of prion protein knockout mice whose predominate symptom, due to complete loss of PrP, was late‐onset peripheral neuropathy. To our knowledge this is the first case reported of a patient with prion disease who had two different pathogenic variants in PRNP.

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Creutzfeldt-Jakob Disease with a Codon 210 Mutation: First Pathological Observation in a Japanese Patient

Cited by 6 publications

References 15 publications

Clinical and Laboratory Features of Three Rare Chinese V210I gCJD Patients

Clinical and Laboratory Features of Three Rare Chinese V210I gCJD Patients

Characterization of mutations in <em>PRNP</em> (prion) gene and their possible roles in neurodegenerative diseases

A case report of genetic prion disease with two different PRNP variants

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