Effect of the D178N mutation and the codon 129 polymorphism on the metabolism of the prion protein

Prion diseases are thought to be caused by the con-version of the normal, or cellular, prion protein (PrPC) into an abnormal protease-resistant conformation (PrPres). There are three familial forms of human prion disease, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome, and fatal familial in-somnia (FFI) which are all expressed at advanced age despite the congenital presence of the mutant prion pro-tein (PrPM). The cellular mechanisms that result in the age-dependent conversion of PrPM into PrPres and the unique phenotypes associated with each PrPM are un-known. FFI and a familial type of Creutzfeldt-Jakob disease (CJD178), share the D178N mutation in the PrP gene but have distinct phenotypes linked to codon 129, the site of a methionine/valine polymorphism (129M/V)