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

Sporadic Creutzfeldt‐Jakob disease in a young Dutch valine homozygote: Atypical molecular phenotype

“…It is undoubtedly true that the cortical PrP res glycoform ratio can distinguish between sCJD and vCJD in the vast majority of cases 7, 8. However, glycoform ratios resembling those seen in vCJD have been reported previously in fatal familial insomnia,16 P102L Gerstmann‐Sträussler‐Scheinker disease,17 and E200K familial CJD 18, 19. The finding of such a glycoform ratio in this case of sCJD suggests that caution is required in the diagnosis of vCJD on the basis of glycoform ratio in the absence of any other confirmatory evidence.…”

Insomnia associated with thalamic involvement in E200K Creutzfeldt–Jakob disease

“…13 Methionine homozygosity at residue 129, as seen in the current case, has been demonstrated in 78% of cases of CJD E200K reported in Libyan Jews. [21][22][23] Further studies are needed to understand the molecular basis underlying the phenotypic variability among patients carrying the PRNP E200K mutation, particularly in those with insomnia. The clinical symptoms include peripheral neuropathy, pruri-tus, insomnia, protracted dementia, or both for several years.…”

Pathogenic Mutations in the Hydrophobic Core of the Human Prion Protein Can Promote Structural Instability and Misfolding

“…In contrast, F198S has been reported to occur with V129 62. This polymorphic site is implicated in disease susceptibility63 and phenotypical differences 64–67. However, studies with F198S recPrP are usually performed with M129 in the protein construct 15,16,24,41,68.…”