NR AUAS
AU Hill,A.F.; Joiner,S.; Beck,J.A.; Campbell,T.A.; Dickinson,A.; Poulter,M.; Wadsworth,J.D.F.; Collinge,J.
TI Distinct glycoform ratios of protease resistant prion protein associated with PRNP point mutations
QU Brain: A Journal of Neurology 2006 Mar; 129(3): 676-85
PT journal article
AB 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 (PrPsc) 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 PrPsc 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 PrPsc with distinct conformations. These data extend the spectrum of recognized PrPsc types seen in human prion diseases and provide further insight into the generation of diverse clinicopathological phenotypes associated with inherited prion disease.
MH Creutzfeldt-Jakob Syndrome/genetics/metabolism; Endopeptidase K; Glycosylation; Humans; Immunoblotting/methods; Oligopeptides/genetics; Phenotype; *Point Mutation; PrPsc Proteins/analysis/metabolism; Prion Diseases/*genetics/metabolism; Prions/*genetics; Research Support, Non-U.S. Gov't; Spleen/chemistry; Tonsil/chemistry
AD Andrew F. Hill, Department of Biochemistry & Molecular Biology, Bio21 Molecular Science and Biotechnology, Institute and Department of Pathology, University of Melbourne, Parkville, Victoria 3010, Australia; Susan Joiner, Jonathan A. Beck, Tracy A. Campbell, Andrew Dickinson, Mark Poulter, Jonathan D. F. Wadsworth and John Collinge, MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
SP englisch
PO England