title: Distinct glycoform ratios of protease resistant prion protein associated with PRNP point mutations.
abstract: Inherited prion diseases are neurodegenerative disorders caused by autosomal dominant mutations in the human prion protein gene (PRNP). Kindred with inherited prion disease can show remarkable phenotypic variability that has yet to be explained. Here we report analysis of protease resistant disease-related prion protein (PrP(Sc)) isoforms from a range of inherited prion disease cases (point mutations P102L, D178N, E200K and 2-, 4- and 6-octapeptide repeat insertions) and show that the glycoform ratios of PrP(Sc) associated with PRNP point mutations are distinct from those observed in sporadic, iatrogenic and variant Creutzfeldt-Jakob disease. Patients with the same PRNP mutation can also propagate PrP(Sc) with distinct conformations. These data extend the spectrum of recognized PrP(Sc) types seen in human prion diseases and provide further insight into the generation of diverse clinicopathological phenotypes associated with inherited prion disease.
authors.affiliation: MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Hill
authors.forename: Susan
authors.initials: S
authors.lastname: Joiner
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Beck
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Campbell
authors.forename: Andrew
authors.initials: A
authors.lastname: Dickinson
authors.forename: Mark
authors.initials: M
authors.lastname: Poulter
authors.forename: Jonathan D F
authors.initials: JD
authors.lastname: Wadsworth
authors.forename: John
authors.initials: J
authors.lastname: Collinge
mesh_terms: D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000378:metabolism; D019286:Endopeptidase K; D006031:Glycosylation; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D009842:Oligopeptides / Q000235:genetics; D014066:Palatine Tonsil / Q000737:chemistry; D010641:Phenotype; D017354:Point Mutation; D018620:PrPSc Proteins / Q000032:analysis / Q000378:metabolism; D017096:Prion Diseases / Q000235:genetics* / Q000378:metabolism; D011328:Prions / Q000235:genetics*; D013154:Spleen / Q000737:chemistry
chemical_list: D009842:Oligopeptides; D018620:PrPSc Proteins; D011328:Prions; D019286:Endopeptidase K