Given the profound effect that codon 129 mismatch in wild-type PrP has in controlling disease pathogenesis in sporadic and acquired CJD (where heterozygosity at codon 129 is thought to confer resistance to prion disease by inhibiting homologous protein-protein interactions [71,74–76] and the presence of 129M or 129V controls the propagation of distinct human prion strains via conformational selection [2,9,15,18–20]), we looked for similar effects in IPD A117V patients. Here, PRNP is linked to prion disease.