New topics in familial prion diseases

Piero Parchi, Robert B. Petersen, Pierluigi Gambetti

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations


Major advances have been made in the understanding of the molecular basis of phenotypic variability in human prion diseases over the last few years. Strong evidence indicates that a complex interaction between specific mutations and the polymorphic codon 129 of the prion protein gene (PRNP) underlies the genetic control of phenotypic expression in familial human prion diseases. Fatal familial insomnia (FFI) and a subtype of familial CJD (CJD178), two prion diseases with different clinico-pathological features, the same mutation at codon 178 of PRNP but a different amino acid at codon 129 of the mutant PRNP allele, represent the best characterized example of this complex interplay between the PRNP genotype and phenotypic variability. Protein studies have subsequently shown that the different genotype of the mutant allele in FFI and CJD178 results in the formation of two different protease-resistant prion proteins (PrP(r)es) which differ in size and glycosylation. These biochemical characteristics of PrP(r)es as well as differences among distinct brain regions in the timing and rate of PrP(r)es deposition and in the vulnerability to PrP(r)es also appear to be major determinants of phenotypic expression in human prion diseases.

Original languageEnglish
Pages (from-to)181-187
Number of pages7
JournalSeminars in Virology
Issue number3
StatePublished - Jun 1996


  • Brain mapping
  • Creutzfeldt-Jakob disease
  • DNA polymorphism
  • Fatal familial insomnia
  • Prion protein


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