Inherited prion disease caused by the V210I mutation

Objective: To describe the clinical and neuropathologic profile and determine the strain characteristics of familial Creutzfeldt–Jakob disease (fCJD) caused by a point mutation of the PRNP gene at codon 210 that results in a valine-to-isoleucine substitution in the prion protein (PrP). Methods: The clinicopathologic features of four individuals from the United States who died of fCJD(V210I) were compared. Transgenic (Tg) mice expressing a chimeric human–mouse PrP transgene were inoculated with brain extracts from three fCJD(V210I) cases, sporadic CJD (sCJD), fCJD(E200K), and fatal familial insomnia (FFI), to compare prion strain characteristics. Results: The clinicopathologic profile of fCJD(V210I) was variable among cases but shared similarities with sCJD. The pattern of PrP^Sc deposition in the brains of Tg mice was similar to that caused by sCJD but different from that associated with fCJD(E200K) or FFI. Conclusions: Each of these prion diseases is characterized by a rapidly progressive dementia with myoclonus, periodic complexes on EEG, and spongiform change without PrP plaque deposition in the brain. The occurrence of a different PrP^Sc phenotype with each PRNP mutation argues that each respective amino acid sequence substitution produces a different prion strain.