TY - JOUR
T1 - Phenotypic variability of Gerstmann-Straussler-Scheinker disease is associated with prion protein heterogeneity
AU - Piccardo, Pedro
AU - Dlouhy, Stephen R.
AU - Lievens, Patricia M.J.
AU - Young, Katherine
AU - Bird, Thomas D.
AU - Nochlin, David
AU - Dickson, Dennis W.
AU - Vinters, Harry V.
AU - Zimmerman, Thomas R.
AU - Mackenzie, Ian R.A.
AU - Kish, Stephen J.
AU - Ang, Lee Cyn
AU - De Carli, Charles
AU - Pocchiari, Maurizio
AU - Brown, Paul
AU - Gibbs, Clarence J.
AU - Gajdusek, D. Carlton
AU - Bugiani, Orso
AU - Ironside, James
AU - Tagliavini, Fabrizio
AU - Ghetti, Bernardino
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1998/10
Y1 - 1998/10
N2 - Gerstmann-Straussler-Scheinker disease (GSS), a cerebello-pyramidal syndrome associated with dementia and caused by mutations in the prion protein gene (PRNP), is phenotypically heterogeneous. The molecular mechanisms responsible for such heterogeneity are unknown. Since we hypothesize that prion protein (PrP) heterogeneity may be associated with clinico-pathologic heterogeneity, the aim of this study was to analyze PrP in several GSS variants. Among the pathologic phenotypes of GSS, we recognize those without and with marked spongiform degeneration. In the latter (i.e. a subset of GSS P102L patients) we observed 3 major proteinase-K resistant PrP (PrPres) isoforms of ca. 21-30 kDa, similar to those seen in Creutzfeldt- Jakob disease. In contrast, the 21-30 kDa isoforms were not prominent in GSS variants without spongiform changes, including GSS A117V, GSS D202N, GSS Q212P, GSS Q217R, and 2 cases of GSS P102L. This suggests that spongiform changes in GSS are related to the presence of high levels of these distinct 21-30 kDa isoforms. Variable amounts of smaller, distinct PrPres isoforms of ca. 7-15 kDa were seen in all GSS variants. This suggests that GSS is characterized by the presence PrP isoforms that can be partially cleaved to low molecular weight PrPres peptides.
AB - Gerstmann-Straussler-Scheinker disease (GSS), a cerebello-pyramidal syndrome associated with dementia and caused by mutations in the prion protein gene (PRNP), is phenotypically heterogeneous. The molecular mechanisms responsible for such heterogeneity are unknown. Since we hypothesize that prion protein (PrP) heterogeneity may be associated with clinico-pathologic heterogeneity, the aim of this study was to analyze PrP in several GSS variants. Among the pathologic phenotypes of GSS, we recognize those without and with marked spongiform degeneration. In the latter (i.e. a subset of GSS P102L patients) we observed 3 major proteinase-K resistant PrP (PrPres) isoforms of ca. 21-30 kDa, similar to those seen in Creutzfeldt- Jakob disease. In contrast, the 21-30 kDa isoforms were not prominent in GSS variants without spongiform changes, including GSS A117V, GSS D202N, GSS Q212P, GSS Q217R, and 2 cases of GSS P102L. This suggests that spongiform changes in GSS are related to the presence of high levels of these distinct 21-30 kDa isoforms. Variable amounts of smaller, distinct PrPres isoforms of ca. 7-15 kDa were seen in all GSS variants. This suggests that GSS is characterized by the presence PrP isoforms that can be partially cleaved to low molecular weight PrPres peptides.
KW - Gerstmann-Straussler-Scheinker disease (GSS)
KW - Immunoblot
KW - PrP gene (PRNP)
KW - Prion protein (PrP)
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U2 - 10.1097/00005072-199810000-00010
DO - 10.1097/00005072-199810000-00010
M3 - Article
C2 - 9786248
AN - SCOPUS:0031754291
SN - 0022-3069
VL - 57
SP - 979
EP - 988
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
IS - 10
ER -