A valine to isoleucine mutation at residue 180 was identified in a French patient with Creutzfeldt-Jakob disease (CJD). The mutation is located in the close vicinity of one of the two N-glycosylation sites of the cellular prion protein (PrP(C)). Western blot analysis revealed accumulation in the brain of the pathogenic proteinase K-resistant PrP (PrP(Sc)) isoform with the notable absence of the diglycosylated band. The mutant protein expressed in CHO cells was correctly glycosylated, suggesting that the atypical glycosylation pattern of PrP(Sc) was not due to the mutation at position 180. These results suggest that the diglycosylated form of the mutant PrP(180I) prevents its conversion into the pathogenic mutant form PrP(Sc180I), supporting a central role of N-linked glycan chains in the PrP conversion process.