PRNP and prion disease: From a historical perspective, the discovery of GSS-specific PRNP mutations and the demonstration that the genotype at the polymorphic codon 129 in the mutated PRNP allele is responsible for the strikingly different phenotypes between two familial prion diseases linked to the same mutation (i.e., D178N), first demonstrated the role that the PRNP genotype plays in genetic prion disease [21,22].