Evidence map›Paper›PMID 40156621›Full record

ArticleJournal of neurology2025

PRNP E146G mutation inherited prion disease: distinctive clinical, pathological and fluid biomarker features.

Thomas Coysh, Zane Jaunmuktane, Laszlo L P Hosszu, Nour Majbour, Fuquan Zhang, Tracy Campbell, Lee Darwent, Marcelo Barria Matus, Edgar Chan, Leah Holm-Mercer and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Thomas CoyshMRC Prion Unit at UCL, UCL Institute of Prion Diseases, 33 Cleveland Street, London, W1W 7FF, UK.
Zane JaunmuktaneDepartment of Neuropathology, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.
Laszlo L P HosszuMRC Prion Unit at UCL, UCL Institute of Prion Diseases, 33 Cleveland Street, London, W1W 7FF, UK.
Nour MajbourMRC Prion Unit at UCL, UCL Institute of Prion Diseases, 33 Cleveland Street, London, W1W 7FF, UK.
Fuquan ZhangMRC Prion Unit at UCL, UCL Institute of Prion Diseases, 33 Cleveland Street, London, W1W 7FF, UK.
Tracy CampbellMRC Prion Unit at UCL, UCL Institute of Prion Diseases, 33 Cleveland Street, London, W1W 7FF, UK.
Lee DarwentMRC Prion Unit at UCL, UCL Institute of Prion Diseases, 33 Cleveland Street, London, W1W 7FF, UK.
Marcelo Barria MatusNational CJD Research & Surveillance Unit, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, EH16 4SB, UK.
Edgar ChanNational Prion Clinic, University College London Hospitals NHS Foundation Trust, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.
Leah Holm-MercerMRC Prion Unit at UCL, UCL Institute of Prion Diseases, 33 Cleveland Street, London, W1W 7FF, UK.
Tze How MokMRC Prion Unit at UCL, UCL Institute of Prion Diseases, 33 Cleveland Street, London, W1W 7FF, UK.
Jonathan D F WadsworthMRC Prion Unit at UCL, UCL Institute of Prion Diseases, 33 Cleveland Street, London, W1W 7FF, UK.
Jan BieschkeMRC Prion Unit at UCL, UCL Institute of Prion Diseases, 33 Cleveland Street, London, W1W 7FF, UK.
Kannan NithiDepartment of Neurology, Northampton General Hospital NHS Trust, Cliftonville, Northampton, NN1 5BD, UK.
Sebastian BrandnerDepartment of Neuropathology, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.
Colin SmithNational CJD Research & Surveillance Unit, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, EH16 4SB, UK.
Margaret EsiriDepartment of Neuropathology, West Wing, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK.
John CollingeMRC Prion Unit at UCL, UCL Institute of Prion Diseases, 33 Cleveland Street, London, W1W 7FF, UK.
Simon MeadMRC Prion Unit at UCL, UCL Institute of Prion Diseases, 33 Cleveland Street, London, W1W 7FF, UK. s.mead@prion.ucl.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Inherited prion diseases (IPDs) are phenotypically diverse neurodegenerative conditions caused by mutations in the prion protein gene (PRNP). We describe IPD due to a novel PRNP E146G mutation in a 50-year-old man presenting with slowly progressive dysarthria, prominent myoclonus especially in the lower limbs, and less prominent gait ataxia, pyramidal and extrapyramidal signs. Cognitive impairment was not overt at disease onset. MRI revealed cerebellar atrophy and white matter hyperintensities. His 46-year-old sister carries the mutation and has subtle gait ataxia and dysarthria. Both patients exhibit a distinctive fluid biomarker profile: in CSF S100B is > twofold upper limit of normal, total tau is moderately elevated, and neurofilament light chain, 14-3-3 and RT-QuIC are negative; in plasma there is marked elevation of GFAP but repeatedly normal neurofilament light chain. The proband's father died aged 55 following an 8-year dementing illness with similar presentation. Post-mortem revealed cerebellar cortical atrophy and profuse large PrP amyloid plaques across cerebral and cerebellar grey matter. Immunoblotting identified low molecular weight protease-resistant PrP fragments. E146G mutation IPD broadly fits into the historical Gerstmann-Sträussler-Scheinker disease spectrum but, based on deep clinical phenotyping of this initial pedigree, we highlight some distinctive features, which may aid in identification of this disease.

Indexed as

MutationPrion DiseasesPrion ProteinsBiomarkersBrainFemaleHumansMaleMiddle AgedBiomarkersPrion ProteinsPRNP protein, humanBiomarkersInherited prion diseaseMutationNeurodegenerationPathologyPrion

Identifiers

PMID40156621
PMCPMC11954691

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.