CJD PRNP

Inherited or familial Creutzfeldt-Jakob disease (fCJD) is a very rare form of genetic prion disease characterized by typical CJD features (rapidly progressive dementia, personality/behavioral changes, psychiatric disorders, myoclonus, and ataxia) with a genetic cause and sometimes a family history of dementia¹.

Prevalence

<0.0225/1,000,000: <15% of CJ variants are repeat expansions². 15% newly diagnosed prion disease cases are genetic³, 1 individual per million per year worldwide (350 cases annually in US)⁴. Found worldwide³.

Age of Onset Details

Typical: 50-60³; Range: 31-63⁵.

Locus

hg19

chr20:4680043-4680139

hg38

chr20:4699397-4699493

t2t

chr20:4738633-4738705

Details

Normal PRNP alleles have one nonapeptide followed by four octapeptide tandem repeat sequences, each of which comprises the amino acids: Pro-(His/Gln)-Gly-Gly-Gly-(-/Trp)-Gly-Gln; any additional repeat leads to pathogenicity, with the largest repeat observed 16 motifs³. Insertion length may correspond to phenotype, such as CJD versus frontotemporal dementia⁶.

Mechanism

LoF?

Loss of function hypothesized⁷

Year

1991⁸

Location in Gene

Coding Exon 2

Gene Strand

Alleles

Ref. Motif

GGTGGTGGCTGGGGGCAGCCTCAT

Pathogenic (ref.)

CCTCATGGTGGTGGCTGGGGGCAG

Pathogenic (gene)

AGCCTCATGGTGGTGGCTGGGGGC

gnomAD

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0007403

Resources for Genetics Professionals — Genetic Disorders Caused by Nucleotide Repeat Expansions and Contractions

Stephanie E.,Wallace, Lora JH,Bean

GeneReviews® [Internet] · 2022-10-20

genereviews:NBK535148

Genetic Prion Disease

Inga,Zerr, Matthias,Schmitz

GeneReviews® · 1993-01-01

genereviews:NBK1229

pmid:29939637

Genetic screening for Huntington disease phenocopies in Sweden: A tertiary center case series focused on short tandem repeat (STR) disorders.

Martin,Paucar, José,Laffita-Mesa, Valter,Niemelä, Helena,Malmgren, Inger,Nennesmo, Kristina,Lagerstedt-Robinson, Magnus,Nordenskjöld, Per,Svenningsson

Journal of the neurological sciences · 2023-06-10

pmid:37379724

Genetic Creutzfeldt‒Jakob disease with 5-octapeptide repeats presented as frontotemporal dementia.

Shinsuke,Hamada, Ikuko,Takahashi-Iwata, Katsuya,Satoh, Tetsuyuki,Kitamoto, Hidehiro,Mizusawa, Fumio,Moriwaka, Ichiro,Yabe

Human genome variation · 2023-03-29

pmid:36977684

Sequence composition changes in short tandem repeats: heterogeneity, detection, mechanisms and clinical implications.

Indhu-Shree,Rajan-Babu, Egor,Dolzhenko, Michael A,Eberle, Jan M,Friedman

Nature reviews. Genetics · 2024-03-11

pmid:38467784

Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene.

L G,Goldfarb, P,Brown, W R,McCombie, D,Goldgaber, G D,Swergold, P R,Wills, L,Cervenakova, H,Baron, C J,Gibbs, D C,Gajdusek

Proceedings of the National Academy of Sciences of the United States of America · 1991-12-01

pmid:1683708

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

Repeat Variants, Biomarkers, and Molecular Signatures in Parkinson's Disease:

Jose Miguel,Laffita-Mesa, Martin,Paucar, Per,Svenningsson

International journal of molecular sciences · 2025-09-20

pmid:41009775

Highly conserved prion protein sequences in random bred cats with three novel synonymous PRNP gene variants.

Canan,Güven, Iraz,Akış

Topics in companion animal medicine · 2025-08-11

pmid:40803449

Clinical, neuropathological, and molecular characteristics of rapidly progressive dementia with Lewy bodies: a distinct clinicopathological entity?

Giuseppe Mario,Bentivenga, Simone,Baiardi, Andrea,Mastrangelo, Edoardo,Ruggeri, Angela,Mammana, Alice,Ticca, Marcello,Rossi, Sabina,Capellari, Piero,Parchi

Alzheimer's research & therapy · 2024-09-10

pmid:39256877

Clinical and Molecular Findings of Intermediate Allele Carriers in the HTT Gene from the Mexican Mestizo Population.

Miguel Ángel,Ramírez-García, David José,Dávila-Ortiz de Montellano, Leticia,Martínez-Ruano, Adriana,Ochoa-Morales, Sandra,Romero-Hidalgo, Juan Carlos,Zenteno, Petra,Yescas-Gómez

Neuro-degenerative diseases · 2022-08-04

pmid:35926480

Novel Polymorphisms and Genetic Characteristics of the Prion Protein Gene in Pheasants.

Kyung Han,Kim, Yong-Chan,Kim, Byung-Hoon,Jeong

Frontiers in veterinary science · 2022-07-12

pmid:35903139

Genetic landscape of early-onset dementia in Hungary.

Dora,Csaban, Anett,Illes, Toth-Bencsik,Renata, Peter,Balicza, Klara,Pentelenyi, Viktor,Molnar, Andras,Gezsi, Zoltan,Grosz, Aniko,Gal, Tibor,Kovacs, Peter,Klivenyi, Maria Judit,Molnar

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022-06-25

pmid:35752680

Prion protein gene mutation detection using long-read Nanopore sequencing.

François,Kroll, Athanasios,Dimitriadis, Tracy,Campbell, Lee,Darwent, John,Collinge, Simon,Mead, Emmanuelle,Vire

Scientific reports · 2022-05-18

pmid:35585119

Co-incidental C9orf72 expansion mutation-related frontotemporal lobar degeneration pathology and sporadic Creutzfeldt-Jakob disease.

Sigrid,Klotz, Theresa,König, Marcus,Erdler, Andreas,Ulram, Anita,Nguyen, Thomas,Ströbel, Alexander,Zimprich, Elisabeth,Stögmann, Günther,Regelsberger, Romana,Höftberger, Herbert,Budka, Gabor G,Kovacs, Ellen,Gelpi

European journal of neurology · 2020-12-01

pmid:33131137

Absence of single nucleotide polymorphisms (SNPs) in the open reading frame (ORF) of the prion protein gene (PRNP) in a large sampling of various chicken breeds.

Yong-Chan,Kim, Sae-Young,Won, Byung-Hoon,Jeong

BMC genomics · 2019-12-03

pmid:31795947