Type 1 protease resistant prion protein and valine homozygosity at codon 129 of PRNP identify a subtype of sporadic Creutzfeldt-Jakob disease

A man was studied with sporadic Creutzfeldt-Jakob disease (sCJD) who had se rial cortical syndromes evolving over 15 months without significant ataxia, prominent myoclonus, or periodic complexes on EEG examinations. This clini cal phenotype correlated with a predominantly cortical and striatal distrib ution of lesions and accumulation of protease resistant prion protein with relative sparing of the brainstem or cerebellum. No amyloid plaques were se en and prion protein (PrP) immunohistochemistry only demonstrated very fain t granular deposits in the cerebral cortex. Molecular analysis showed homoz ygosity for valine at codon 129 in the prion protein gene (PRNP) and protea se resistant prion protein type 1 deposition. The comparison of molecular a nd clinicopathological features of the present case with those previously r eported in sCJD, indicates that valine homozygosity at codon 129 and type 1 protease resistant prion protein are associated with a distinct phenotypic variant of sCJD. The data also support the view that the PRNP codon 129 po lymorphism and the physicochemical properties of the protease resistant pri on protein are major determinants of phenotypic variability in sCJD.