Journal of Neurology

, Volume 249, Issue 11, pp 1567–1582

Mutations of the Prion Protein Gene

Phenotypic Spectrum

Authors

  • Gábor G. Kovács
    • Institute of Neurology, University of Vienna, and Austrian Reference Centre for Human Prion Diseases, Vienna, Austria
  • Gianriccardo Trabattoni
    • Institute of Neurology, University of Vienna, and Austrian Reference Centre for Human Prion Diseases, Vienna, Austria
  • Johannes A. Hainfellner
    • Institute of Neurology, University of Vienna, and Austrian Reference Centre for Human Prion Diseases, Vienna, Austria
  • James W. Ironside
    • National CJD Surveillance Unit, University of Edinburgh, Western General Hospital, Edinburgh, UK
  • Richard S. G. Knight
    • National CJD Surveillance Unit, University of Edinburgh, Western General Hospital, Edinburgh, UK
  • Herbert Budka
    • Institute of Neurology, University of Vienna, and Austrian Reference Centre for Human Prion Diseases, Vienna, Austria
ORIGINAL COMMUNICATION

DOI: 10.1007/s00415-002-0896-9

Cite this article as:
Kovács, G., Trabattoni, G., Hainfellner, J. et al. J Neurol (2002) 249: 1567. doi:10.1007/s00415-002-0896-9

Abstract.

Prion diseases are inherited in 5–15 % of cases. They are classified according to changes in the prion protein gene (PRNP) or conventionally according to phenotype as Gerstmann-Sträussler-Scheinker disease (GSS), fatal familial insomnia (FFI), or familial Creutzfeldt-Jakob disease (fCJD). Point mutations and insertions within PRNP form the genetic background. We report the results of a systematic analysis of over 500 case reports of patients with PRNP abnormalities. We compare clinical, neuropathological and molecular data in five groups, namely GSS, FFI, fCJD, base pair insertion (BPI), and all cases collectively. Clinical presentation overlaps between mutations, but some have characteristic features (e. g. P105L, D178N–129M, T183A). Some mutations, especially in the lack of sufficient family history, in earlier phases tend to resemble other neurodegenerative disorders like multiple system atrophy, corticobasal degeneration or familial diseases such as late-onset spinocerebellar ataxia, spastic paraparesis, frontotemporal dementia, or Alzheimer's disease. The codon 129 polymorphism has a phenotypic influence in inherited prion diseases, as in non-genetic forms, but additional factors might be considered as background for phenotypic variability.

Key words prion protein geneCreutzfeldt-Jakob diseaseGerstmann-Sträussler-Scheinker diseasefatal familial insomniabase pair insertion

Copyright information

© Steinkopff Verlag 2002