title: Creutzfeldt-Jakob disease (CJD) with a mutation at codon 148 of prion protein gene: relationship with sporadic CJD.
abstract: Creutzfeldt-Jakob disease (CJD), the most common human prion disease, includes sporadic (s) and familial (f) forms. Regardless of etiology, both forms are thought to share the pathogenic mechanism whereby the cellular prion protein (PrP(C)) converts into its pathogenic isoform (PrP(Sc)). While PrP(C) conversion is thought to be random in sCJD, conversion in fCJD is facilitated by the congenital presence of mutated PrP. Differences in PrP genotype (PRNP) and in conversion circumstances lead to PrP(Sc) with distinct characteristics that elicit different disease phenotypes. Here, we describe a case of fCJD with a substitution of histidine (H) for arginine (R) at codon 148 (R148H) and heterozygosity of the methionine/valine (M/V) polymorphic codon 129, with the 129M allele coupled with the mutation. The disease phenotype and all major characteristics of PrP(Sc) of fCJD(R148H) were virtually indistinguishable from those of sCJDMV2, which has features different from those of any other sCJD. Therefore, despite the differences in etiology, PRNP, and conversion process, the two forms of PrP(Sc) had similar characteristics. Furthermore, comparison of fCJD(R148H) with a recently reported case carrying R148H and homozygosity at codon 129 suggests that codon 129 coupled with the mutation as well as that located on the normal allele can modify major phenotypic and PrP(Sc) features of fCJD(R148H).
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Manuela
authors.initials: M
authors.lastname: Pastore
authors.forename: Steven S
authors.initials: SS
authors.lastname: Chin
authors.forename: Karen L
authors.initials: KL
authors.lastname: Bell
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Dong
authors.forename: Qiwei
authors.initials: Q
authors.lastname: Yang
authors.forename: Lizhu
authors.initials: L
authors.lastname: Yang
authors.forename: Jue
authors.initials: J
authors.lastname: Yuan
authors.forename: Shu G
authors.initials: SG
authors.lastname: Chen
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Gambetti
authors.forename: Wen-Quan
authors.initials: WQ
authors.lastname: Zou
mesh_terms: D019943:Amino Acid Substitution; D001344:Autopsy; D001921:Brain / Q000473:pathology; D003062:Codon / Q000235:genetics; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics* / Q000473:pathology; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine; D008875:Middle Aged; D009154:Mutation; D016366:Open Reading Frames; D010375:Pedigree; D010641:Phenotype; D018621:PrPC Proteins / Q000235:genetics*; D018620:PrPSc Proteins / Q000235:genetics*; D011487:Protein Conformation; D014633:Valine
chemical_list: D003062:Codon; D018621:PrPC Proteins; D018620:PrPSc Proteins; D008715:Methionine; D014633:Valine