Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease

Nature. 1991 Jul 25;352(6333):340-2. doi: 10.1038/352340a0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Creutzfeldt-Jakob Syndrome / genetics*
  • Homozygote
  • Humans
  • Molecular Sequence Data
  • Open Reading Frames
  • Polymerase Chain Reaction
  • PrPSc Proteins
  • Scrapie / genetics
  • Viral Proteins / genetics*


  • PrPSc Proteins
  • Viral Proteins