NR AOXT
AU Pastore,M.; Zou,W.Q.; Castellani,R.J.; Colucci,M.; Chen,S.G.; Hua,Z.; Bell,K.L.; Chin,S.S.M.; Gambetti,P.
TI R148H: identikit of a novel prion protein gene mutation associated with CJD phenotype
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - DG-74
PT Konferenz-Poster
AB
Familial prion diseases are commonly grouped in familial Creutzfeldt-Jakob disease (CJD), fatal familial insomnia (FFI) and Gerstmann-Sträussler-Scheinker disease (GSS) according to their phenotype. In familial CJD (fCJD) the pathological features often mimic those of subtypes of sporadic CJD (sCJD). For example, fCJD E200K reproduces often the histopathologial features of the sporadic CJD subtype that is associated with metionine homozygosity at codon 129 and type 1 scrapie prion protein (sCJD MM1); fCJD D178N resembles sCJD with valine homozygosity at codon 129 and type 1 scrapie prion protein (sCJD VV1).
Here we report a novel PRNP mutation associated with a new phenotype mimicking sCJD with heterozygosity and type 2 scrapie prion protein (sCJD MV2). Despite the phenotypic similarities we observed significant differences in the PrPsc characteristics.
At variance with one-dimensional (1-D) immunoblot, the 2-D immunoblots revealed differences in number and localizations of PrPsc isoforms between sCJD MV2 and fCJD R148H. The two PrPsc species differ also in the solubility immunoassay: the PrPsc associated with the mutation being more resistant to guanidine hydrochloride denaturation than that from sCJD. The affinity to PrPsc of antibodies directed to the 148 residue region was also different by dot-blot analysis.
Our findings suggest that although the pathological phenotype of fCJD may match that of a sCJD, characterization of the PrPsc reveals that the familial and sporadic forms are associated with distinct PrPsc strains, probably due to the presence of the mutation.
AD Manuela Pastore, Wen-Quan Zou, Rudy J. Castellani, Monica Colucci, Shu G. Chen, Pierluigi Gambetti, Division of Neuropathology, Department of Pathology, Case Western Reserve University, Cleveland, OH, USA; Zhoungxue Hua, Karen L. Bell, Steven S. Chin, Division of Neuropathology, Department of Pathology, College of Physician and Surgeons of Columbia University, New York, NY, USA
SP englisch
PO Deutschland