Polymorphism at codon 129 of PRNP affects the phenotypic expression of Creutzfeldt-Jakob disease linked to E200K mutation.

Recently, Hainfellner and colleagues1 reported on a novel phenotype of familial Creutzfeldt-Jakob disease (CJD) asso- ciated with the E200K mutation in the prion protein gene (PRNP) in coupling with valine at codon 129. At difference with the E200K mutation coupled with methionine 129, which is characterized by diffuse PrPres immunoreactivity at the histological examination of the brain and type 1 PrPres immunoreactivity pattern on immunoblot,2 E200K-129V exhibited plaque-like and type 2 immunoreactivity, support- ing the view that the genotype at codon 129 of the mutated PRNP allele influences disease phenotype. We have recently observed another CJD patient carrying the E200K-129V haplotype, but heterozygous at codon 129. Comparison be- tween this and Hainfellner’s case allows an evaluation of the role of codon 129 genotype of the normal allele in disease expression