A new point mutation of the prion protein gene in Creutzfeldt‐Jakob disease

Pocchiari, Maurizio; Salvatore, Mirella; Cutruzzolà, Francesca; Genuardi, Maurizio; Allocatelli, Carlo Travaglini; Masullo, Carlo; Macćhi, G; Alemà, G; Galgani, Simona; Xi, You Geng; Petraroli, Rosella; Silvestrini, Maria Chiara; Brunori, Maurizio

doi:10.1002/ana.410340608

Cited by 103 publications

(41 citation statements)

References 29 publications

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“…The clinical and neuropathological features described in the Italian, French and Japanese patients were very similar to those of sporadic CJD with a rapid evolution to death (mean, 4.1 months) [12][13][14] . However, the Italian case had a new 24-bp delection in the other allele 13 .…”

Section: Discussionmentioning

confidence: 52%

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Familial Creutzfeldt-Jakob disease associated with a point mutation at codon 210 of the prion protein gene

Huang

Marie

Kok

et al. 2001

Arq. Neuro-Psiquiatr.

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-Creutzfeldt-Jakob disease (CJD), the most known human prion disease, is usually sporadic but approximately 15% of the cases are familial. To date, seven CJD cases with codon 210 mutation (GTT to ATT) have been reported in the literature. We describe a case of a 57 year-old woman who presented gait disturbances and rapidly progressive dementia, leading to death four months after onset. Electroencephalogram revealed periodic activity, diffusion-weighted magnetic resonance imaging showed hypersignal in basal ganglia, and test for 14-3-3 protein was strongly positive in the CSF. The complete prion protein gene coding region was sequenced after PCR amplification, showing a point mutation in codon 210. This is the first case of CJD with codon 210 mutation diagnosed in Brazil. We emphasize the role of genetic search for prion protein gene mutation, even in patients presenting clinical features resembling sporadic CJD.KEY WORDS: familial Creutzfeldt-Jakob disease, prion protein gene mutation, codon 210, 14-3-3 protein. Doença de Creutzfeldt-Jakob familial com mutação pontual no codon 210 do gene da proteína priônicaRESUMO -A doença de Creutzfeldt-Jakob (DCJ), a mais conhecida das doenças priônicas, é usualmente esporádica, mas cerca de 15% dos casos são familiais. Sete casos de DCJ familial com mutação no codon 210 (GTT→ATT) foram relatados na literatura até o presente momento. Nós descrevemos o caso de uma mulher de 57 anos com distúrbios de marcha e demência rapidamente progressiva, evoluindo para óbito em 4 meses. Eletroencefalograma revelou atividade periódica, ressonância magnética com técnica de difusão mostrou hipersinal em gânglios da base e teste para proteína 14-3-3 no líquido cefalorraqueano foi fortemente positivo. A região codificadora do gene da proteína priônica foi sequenciada após a amplificação por PCR, revelando mutação de ponto no codon 210, constituindo-se no primeiro caso com esta mutação diagnosticado no Brasil. Enfatizamos a importância da investigação de mutações do gene da proteína priônica, mesmo em pacientes com quadro típico de DCJ esporádica. PALAVRAS-CHAVE: doença de Creutzfeldt-Jakob familial, codon 210, gene da proteína priônica, mutação, proteína 14-3-3.

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Section: Discussionmentioning

confidence: 52%

“…Including these original cases, a total of 7 such cases with this mutation have been reported in the literature to date: one French patient 12 , one Italian family with two cases 13 , one Japanese patient 14 , two Chinese cases from the same family 15 and one individual from North Africa 16 .…”

Section: Discussionmentioning

confidence: 99%

Familial Creutzfeldt-Jakob disease associated with a point mutation at codon 210 of the prion protein gene

Huang

Marie

Kok

et al. 2001

Arq. Neuro-Psiquiatr.

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“…In addition to these synaptic patterns, we also identified a plaque staining pattern in the occipital lobes that was positive for thioflavin-T as well as MM1. Whether these pathological findings are specific to this type of mutation remains to be determined, as pathological investigations of the V210I mutation are currently insufficient (13)(14)(15). Mastrianni et al summarized the histopathological data of three patients with this type of mutation, and reported nerve cell loss, vacuolation and reactive astrogliosis to be characteristic features resembling those of sporadic CJD.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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We herein report a case of Creutzfeldt-Jakob disease (CJD) with a V210I mutation and discuss the pathological findings. The patient's clinical course was quite similar to that of patients with sporadic CJD. Diffusion-weighted magnetic resonance imaging (MRI) disclosed a high signal intensity in the basal ganglia and cerebral cortices. Pathologically, spongiform degeneration of neurons and their processes with reactive astrocytosis was observed. Prion protein immunostaining revealed diffuse positive and plaque-type patterns. Only one Japanese case of CJD with this type of mutation has been reported to date, but without any pathological examination results. Therefore, this report is considered to be highly significant for understanding CJD.

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“…Another mutation at codon 210 (V2101) that produces familial CJD (55,56) appears to be a site for helix-helix interactions on helix 4 ( Table 1). The V210I mutation would disrupt the helix 4-helix 1 interaction and, thus, perturb the structure ofPrPC (Fig.…”

Section: Methodsmentioning

confidence: 99%

Proposed three-dimensional structure for the cellular prion protein.

Huang

Gabriel²,

Baldwin³

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

169

109

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Prion diseases are a group of neurodegenerative disorders in human and animals that seem to result from a conformatlonal change in the prion protein (PrP). Utilizing data obtained by circular dichroism and in spectroscopy, computational studies prdIe the tedi nal s ture of the cellular form of PrP (PrPC). A heuristic approach consistng of the prediction of so structures and of an evalnation of the pig of s y elements was used to search for plausible teriay strucures. After a series of experimental and theoretical ants were applied, four structural models of four-helix bundles emerged. A group of amino acids within the four predicted helices were Identified as important for tertiary interactions between helices. These amino acids could be essential for ma ining a stable tertiary suture of PrPC. Among four plausible s al models for PrPC, the X-bundle model seemed to correlate best with 5 of 11 known point mutations that segregate with the inherited prion diseases. These 5 mutions cluster around a central hydrophobic core in the X-bundle structure. Furthermore, these mutations occur at or near those amino acds which are predicted to e important for helix-helix interactions. The three-dimensonal structure of

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A new point mutation of the prion protein gene in Creutzfeldt‐Jakob disease

Cited by 103 publications

References 29 publications

Familial Creutzfeldt-Jakob disease associated with a point mutation at codon 210 of the prion protein gene

Familial Creutzfeldt-Jakob disease associated with a point mutation at codon 210 of the prion protein gene

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

Proposed three-dimensional structure for the cellular prion protein.

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