ORIGINAL COMMUNICATION

Journal of Neurology

, Volume 249, Issue 11, pp 1567-1582

First online:

Mutations of the Prion Protein Gene

Phenotypic Spectrum
  • Gábor G. KovácsAffiliated withInstitute of Neurology, University of Vienna, and Austrian Reference Centre for Human Prion Diseases, Vienna, Austria
  • , Gianriccardo TrabattoniAffiliated withInstitute of Neurology, University of Vienna, and Austrian Reference Centre for Human Prion Diseases, Vienna, Austria
  • , Johannes A. HainfellnerAffiliated withInstitute of Neurology, University of Vienna, and Austrian Reference Centre for Human Prion Diseases, Vienna, Austria
  • , James W. IronsideAffiliated withNational CJD Surveillance Unit, University of Edinburgh, Western General Hospital, Edinburgh, UK
  • , Richard S. G. KnightAffiliated withNational CJD Surveillance Unit, University of Edinburgh, Western General Hospital, Edinburgh, UK
  • , Herbert BudkaAffiliated withInstitute of Neurology, University of Vienna, and Austrian Reference Centre for Human Prion Diseases, Vienna, Austria

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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 gene Creutzfeldt-Jakob disease Gerstmann-Sträussler-Scheinker disease fatal familial insomnia base pair insertion