Homozygous prion protein genotype predisposes to sporadic Creutzfeldt–Jakob disease
Abstract
The human prion diseases, Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler syndrome (GSS), are neurodegenerative diseases that are unique in being both infectious and genetic. Transmission of both diseases and the animal spongiform encephalopathies (for example, scrapie and bovine spongiform encephalopathy) to experimental animals by intracerebral inoculation with brain homogenates is well documented. Despite their experimental transmissibility, missense and insertional mutations in the prion protein gene are associated with both GSS and familial CJD, demonstrating that the human familial cases are autosomal dominant diseases. More than 80% of CJD cases occur sporadically, however, and are not known to be associated with mutations. Here we report that 21 of 22 sporadic CJD cases and a further 19 of 23 suspected sporadic CJD cases are homozygous at the polymorphic amino-acid residue 129; 51% of the normal population are heterozygous at this site. We argue that homozygosity predisposes towards sporadic CJD and that this directly supports the hypothesis that interaction between prion protein molecules underlies the disease process.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Multiple mutations in the PRNP gene have been linked to various phenotypes of hereditary, sporadic, and iatrogenic CJD.
“Multiple mutations in the PRNP gene have been linked to various phenotypes of hereditary, sporadic, and iatrogenic CJD (25, 26).”
From Kuru (2012) · cites this paper as [25]
Codon 129 heterozygosity is protective against the development of iatrogenic and sporadic Creutzfeldt-Jakob disease and kuru.
“Codon 129 heterozygosity is protective against the development of iatrogenic 8 and sporadic 9 Creutzfeldt-Jakob disease and kuru 3,[10][11][12] ;”
From A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure (2009) · cites this paper as [9]
Prion propagation is favored by homologous PrP interactions.
“However, prion propagation is favored by homologous PrP interactions.9”
From A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure (2009) · cites this paper as [9]
Cited by
Sorted by citations
p53-Dependent apoptosis suppresses tumor growth and progression in vivo
Symonds, H., Krall, L., Remington, L., Saenz-Robles, M., Lowe, S., Jacks, T., & Van Dyke, T. (1994) · Cell · doi:10.1016/0092-8674(94)90534-7 · Cited by 880 · see citing works
Thirty years of Alzheimer's disease genetics: the implications of systematic meta-analyses
Bertram, L., & Tanzi, R. E. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2494 · Cited by 747 · see citing works
The genetic epidemiology of neurodegenerative disease
Bertram, L. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24761 · Cited by 680 · see citing works
Quantifying prion disease penetrance using large population control cohorts
Minikel, E. V., Vallabh, S. M., Lek, M., Estrada, K., Samocha, K. E., Sathirapongsasuti, J. F., McLean, C. Y., Tung, J. Y., Yu, L. P. C., Gambetti, P., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad5169 · Cited by 442 · see citing works
Kuru in the 21st century—an acquired human prion disease with very long incubation periods
Collinge, J., Whitfield, J., McKintosh, E., Beck, J., Mead, S., Thomas, D. J., & Alpers, M. P. (2006) · The Lancet · doi:10.1016/s0140-6736(06)68930-7 · Cited by 427 · see citing works
Self-citationEssential oils as multicomponent mixtures and their potential for human health and well-being
Bunse, M., Daniels, R., Gründemann, C., Heilmann, J., Kammerer, D. R., Keusgen, M., Lindequist, U., Melzig, M. F., Morlock, G. E., Schulz, H., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.956541 · Cited by 210 · see citing works
A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure
Mead, S., Whitfield, J., Poulter, M., Shah, P., Uphill, J., Campbell, T., Al-Dujaily, H., Hummerich, H., Beck, J., Mein, C. A., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0809716 · Cited by 206 · see citing works
Self-citationKim, M.-O., Takada, L. T., Wong, K., Forner, S. A., & Geschwind, M. D. (2018) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a033134 · Cited by 130 · see citing works
Stys, P. K., You, H., & Zamponi, G. W. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2011.225276 · Cited by 115 · see citing works
Staffaroni, A. M., Kramer, A. O., Casey, M., Kang, H., Rojas, J. C., Orrú, C. D., Caughey, B., Allen, I. E., Kramer, J. H., Rosen, H. J., et al. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2019.1071 · Cited by 100 · see citing works
Familial spongiform encephalopathy associated with a novel prion protein gene mutation
Nitrini, R., Rosemberg, S., Passos‐Bueno, M. R., da Silva, L. S. T., Iughetti, P., Papadopoulos, M., Carrilho, P. M., Caramelli, P., Albrecht, S., Zatz, M., et al. (1997) · Annals of Neurology · doi:10.1002/ana.410420203 · Cited by 106 · see citing works
Liberski, P. P., Sikorska, B., Lindenbaum, S., Goldfarb, L. G., McLean, C., Hainfellner, J. A., & Brown, P. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3182444efd · Cited by 50 · see citing works
“Multiple mutations in the PRNP gene have been linked to various phenotypes of hereditary, sporadic, and iatrogenic CJD (25, 26).”
BackgroundPrion genotypes in Central America suggest selection for the V129 allele
Hardy, J., Scholz, S., Evans, W., Goldfarb, L., & Singleton, A. (2006) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30248 · Cited by 7 · see citing works
- Authors
- Palmer, M. S., Dryden, A. J., Hughes, J. T., & Collinge, J.
- Affiliations
- St Mary's Hospital (GB)
- ORCID
- Collinge, John
- Venue
- Nature
- Published
- 1991-07-25
- Volume
- 352
- Issue
- 6333
- Pages
- 340-342
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2054904323
- Cited by
- 890
- References
- 0
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 20 · 2023: 10 · 2022: 16 · 2021: 18 · 2020: 17 · 2019: 15 · 2018: 21 · 2017: 23 · 2016: 21 · 2015: 21 · 2014: 20 · 2013: 25 · 2012: 32
- FWCI
- 10.44
- Type
- journal article
- Language
- en
- Update notices
- correction (1991-08-08)
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Amyloidosis: Diagnosis, Treatment, Outcomes
- Keywords
- sporadic Creutzfeldt-Jakob disease, prion protein, homozygosity, codon 129 polymorphism, prion protein gene mutation, familial CJD, genetic susceptibility, neurodegenerative diseases
- MeSH terms
- Amino Acid Sequence, Base Sequence, Homozygote, Humans, Creutzfeldt-Jakob Syndrome, Molecular Sequence Data, Scrapie, Viral Proteins, Polymerase Chain Reaction, Open Reading Frames, PrPSc Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
