Curation CJD PRNP

Gene PRNP
Disease CJD
Inheritance AD
Score

7.5 + 1 = 8.5 / 18

Genetic + experimental = total
Classification
0
18
Refuted
Moderate
Definitive
Last Updated 08/14/2025
Pubs Reviewed 4
Publication Span 34.09 years
Publication Interval 34.09 years
Curator(s) Macayla Weiner, Laurel Hiatt
Description

PRNP octapeptide repeat insertions (OPRIs) in the exon 2/N-terminal coding repeat region are associated with autosomal dominant genetic Creutzfeldt-Jakob disease/inherited prion disease. Uploaded sources describe the normal five-octapeptide repeat structure, familial CJD/CJD-GSS cases with expanded alleles, published OPRI genetic CJD case summaries across 1–7 additional repeats, and newer 5-OPRI reports with atypical frontotemporal dementia-like or Huntington disease-like presentations.

Genetic evidence

Total: 7.5

Category
Type
Citation
Score
Details
Singular Evidence
Probands
6

Review summarized published genetic CJD cases with PRNP octapeptide-repeat insertions across 1–7 additional-repeat haplotypes, including 5-OPRI, 6-OPRI, and 7-OPRI groups with variable age at onset, disease duration, family history, and diagnostic findings.

Collective Evidence
Segregation
1.5

Goldfarb et al. screened familial spongiform encephalopathy kindreds and identified expanded PRNP octapeptide-repeat alleles in affected CJD/CJD-GSS families: 10 repeats in Kel, 12 repeats in three tested affected Ald family members with four unaffected relatives carrying normal alleles, and 13 repeats in Che, including the proband and one at-risk niece while another niece was normal.

Experimental evidence

Total: 1

Category
Type
Citation
Score
Details
Function
Biochemical function
0.5

In an HD-phenocopy screening cohort, one patient with inherited prion disease carried PRNP 5-OPRI and Met/Met at codon 129; the authors reported neuropathologically proven prion disease and protease-resistant PrP fragments. This is PRNP OPRI-associated prion biochemistry/pathology rather than a mechanistic functional assay.

Function
Protein interaction
0.5

Gene-level, not OPRI-specific: the clinical CJD review describes pathogenic PrPSc associating with normal cellular PrP and converting alpha-helical PrPC into protease-resistant beta-pleated aggregates; no PRNP OPRI-specific protein-interaction assay was provided.

Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.