PRNP and prion disease: At PRNP, the p.Met129Val polymorphism is known to be a strong modifier of prion disease, determining predisposition to sCJD52 and iatrogenic CJD (iCJD),39 as well as influencing age of disease onset and/or disease progression in kuru41 and some inherited prion diseases,40 where in general the heterozygous genotype is protective compared to both homozygous genotypes.