Creutzfeldt–Jakob disease and other prion diseases

Zerr, Inga; Ladogana, Anna; Mead, Simon; Hermann, Peter; Forloni, Gianluigi; Appleby, Brian S.

doi:10.1038/s41572-024-00497-y

Cited by 14 publications

(3 citation statements)

References 200 publications

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“…sCJD, accounting for nearly 85% of cases, typically presents with rapid cognitive decline, ataxia, and myoclonus [1]. Less common inaugural symptoms include psychiatric disturbances, visual impairments, seizures, and speech disorders [3].…”

Section: Discussionmentioning

confidence: 99%

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Dysarthria as a Presenting Symptom With Rapidly Progressive Imaging Features in Sporadic Creutzfeldt-Jakob Disease: A Case Report

Pan,

Wang

2024

Cureus

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Section: Discussionmentioning

confidence: 99%

“…Its incidence stands at approximately one per million, with an exceedingly diverse clinical presentation. Common manifestations include rapidly progressive dementia, cerebellar ataxia, and myoclonus [1]. Atypical cases, initially presenting with focal neurological deficits, can make diagnosis particularly challenging.…”

Section: Introductionmentioning

confidence: 99%

Dysarthria as a Presenting Symptom With Rapidly Progressive Imaging Features in Sporadic Creutzfeldt-Jakob Disease: A Case Report

Pan,

Wang

2024

Cureus

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“…Human prion disease can arise from infectious, familial, or sporadic origins. Infectious transmission, including kuru, iatrogenically acquired disease, and zoonotic transmission of bovine spongiform encephalopathy, have caused <1% of cases [88]. Most prion disease cases (∼85%) are sporadic (sCJD), while ∼15% of cases are familial.…”

Section: Introductionmentioning

confidence: 99%

Neuropathologically-directed profiling ofPRNPsomatic and germline variants in sporadic human prion disease

McDonough,

Cheng,

Morillo

et al. 2024

Preprint

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Creutzfeldt-Jakob Disease (CJD), the most common human prion disease, is associated with pathologic misfolding of the prion protein (PrP), encoded by thePRNPgene. Of human prion disease cases, ∼1% were transmitted by misfolded PrP, ∼15% are inherited, and ∼85% are sporadic (sCJD). While familial cases are inherited through germline mutations inPRNP, the cause of sCJD is unknown. Somatic mutations have been hypothesized as a cause of sCJD, and recent studies have revealed that somatic mutations accumulate in neurons during aging. To investigate the hypothesis that somatic mutations inPRNPmay underlie sCJD, we performed deep DNA sequencing ofPRNPin 205 sCJD cases and 170 age-matched non-disease controls. We included 5 cases of Heidenhain variant sporadic CJD (H-sCJD), where visual symptomatology and neuropathology implicate focal initiation of prion formation, and examined multiple regions across the brain including in the affected occipital cortex. We employed Multiple Independent Primer PCR Sequencing (MIPP-Seq) with a median depth of >5,000X across thePRNPcoding region and analyzed for variants using MosaicHunter. An allele mixing experiment showed positive detection of variants in bulk DNA at a variant allele fraction (VAF) as low as 0.2%. We observed multiple polymorphic germline variants among individuals in our cohort. However, we did not identify bona fide somatic variants in sCJD, including across multiple affected regions in H-sCJD, nor in control individuals. Beyond our stringent variant-identification pipeline, we also analyzed VAFs from raw sequencing data, and observed no evidence of prion disease enrichment for the known germline pathogenic variants P102L, D178N, and E200K. The lack ofPRNPpathogenic somatic mutations in H-sCJD or the broader cohort of sCJD suggests that clonal somatic mutations may not play a major role in sporadic prion disease. With H-sCJD representing a focal presentation of neurodegeneration, this serves as a test of the potential role of clonal somatic mutations in genes known to cause familial neurodegeneration.

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Prions: structure, function, evolution, and disease

Casey,

Sleator

2024

Arch Microbiol

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Creutzfeldt–Jakob disease and other prion diseases

Cited by 14 publications

References 200 publications

Dysarthria as a Presenting Symptom With Rapidly Progressive Imaging Features in Sporadic Creutzfeldt-Jakob Disease: A Case Report

Dysarthria as a Presenting Symptom With Rapidly Progressive Imaging Features in Sporadic Creutzfeldt-Jakob Disease: A Case Report

Neuropathologically-directed profiling ofPRNPsomatic and germline variants in sporadic human prion disease

Prions: structure, function, evolution, and disease

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