PRNP and prion disease: Several hypotheses have been proposed to explain the molecular basis of spontaneous prion diseases [40]: (a) an aleatory misfolding process that generates PrPSc molecules from PrPC, (b) the presence of somatic mutations in the PrP gene in a reduced number of cells that generate mutant PrP molecules that afterwards template the formation of PrPC into PrPSc and (c) discordances between mRNA sequences and DNA sequences.