title: Variably protease-sensitive prionopathy: a new sporadic disease of the prion protein.
abstract: OBJECTIVE
  The objective of the study is to report 2 new genotypic forms of protease-sensitive prionopathy (PSPr), a novel prion disease described in 2008, in 11 subjects all homozygous for valine at codon 129 of the prion protein (PrP) gene (129VV). The 2 new PSPr forms affect individuals who are either homozygous for methionine (129MM) or heterozygous for methionine/valine (129MV).
  
  
  METHODS
  Fifteen affected subjects with 129MM, 129MV, and 129VV underwent comparative evaluation at the National Prion Disease Pathology Surveillance Center for clinical, histopathologic, immunohistochemical, genotypical, and PrP characteristics.
  
  
  RESULTS
  Disease duration (between 22 and 45 months) was significantly different in the 129VV and 129MV subjects. Most other phenotypic features along with the PrP electrophoretic profile were similar but distinguishable in the 3 129 genotypes. A major difference laid in the sensitivity to protease digestion of the disease-associated PrP, which was high in 129VV but much lower, or altogether lacking, in 129MV and 129MM. This difference prompted the substitution of the original designation with "variably protease-sensitive prionopathy" (VPSPr). None of the subjects had mutations in the PrP gene coding region.
  
  
  CONCLUSIONS
  Because all 3 129 genotypes are involved, and are associated with distinguishable phenotypes, VPSPr becomes the second sporadic prion protein disease with this feature after Creutzfeldt-Jakob disease, originally reported in 1920. However, the characteristics of the abnormal prion protein suggest that VPSPr is different from typical prion diseases, and perhaps more akin to subtypes of Gerstmann-Sträussler-Scheinker disease.
authors.affiliation: Department of Pathology, National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH 44106, USA. wenquan.zou@case.edu
authors.forename: Wen-Quan
authors.initials: WQ
authors.lastname: Zou
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Puoti
authors.forename: Xiangzhu
authors.initials: X
authors.lastname: Xiao
authors.forename: Jue
authors.initials: J
authors.lastname: Yuan
authors.forename: Liuting
authors.initials: L
authors.lastname: Qing
authors.forename: Ignazio
authors.initials: I
authors.lastname: Cali
authors.forename: Miyuki
authors.initials: M
authors.lastname: Shimoji
authors.forename: Jan P M
authors.initials: JP
authors.lastname: Langeveld
authors.forename: Rudy
authors.initials: R
authors.lastname: Castellani
authors.forename: Silvio
authors.initials: S
authors.lastname: Notari
authors.forename: Barbara
authors.initials: B
authors.lastname: Crain
authors.forename: Robert E
authors.initials: RE
authors.lastname: Schmidt
authors.forename: Michael
authors.initials: M
authors.lastname: Geschwind
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Dearmond
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
authors.forename: Dennis
authors.initials: D
authors.lastname: Dickson
authors.forename: Lawrence
authors.initials: L
authors.lastname: Honig
authors.forename: Juan Maria
authors.initials: JM
authors.lastname: Torres
authors.forename: James
authors.initials: J
authors.lastname: Mastrianni
authors.forename: Sabina
authors.initials: S
authors.lastname: Capellari
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giaccone
authors.forename: Ermias D
authors.initials: ED
authors.lastname: Belay
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Schonberger
authors.forename: Mark
authors.initials: M
authors.lastname: Cohen
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Kong
authors.forename: Piero
authors.initials: P
authors.lastname: Parchi
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tagliavini
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Gambetti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000201:enzymology / Q000473:pathology; D004252:DNA Mutational Analysis; D003704:Dementia / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D005260:Female; D005820:Genetic Testing; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000235:genetics* / Q000502:physiology / Q000633:toxicity; D010641:Phenotype; D017096:Prion Diseases / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D011328:Prions / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D011328:Prions; D010447:Peptide Hydrolases