NR AQRS
AU Parchi,P.; Capellari,S.; Sima,A.A.F.; D'Amato,C.; McKeever,P.; Mikol,J.; Brion,S.; Brown,P.; Chen,S.G.; Petersen,R.B.; Gambetti,P.
TI Creutzfeldt-Jakob-disease (CJD) with 178(Asn) mutation in the prion protein gene - neuropathological and molecular-features
QU Journal of Neuropathology and Experimental Neurology 1996; 55(N5): 635 Nr. 121
PT Meeting Abstract
AB The molecular basis of phenotypic variability in human prion diseases has not been fully elucidated. We characterized the pathological phenotype and the pattern of intracerebral deposition and electrophoretic mobility of the protease-resistant protein (PrPres) in 7 CJD affected subjects carrying the 178ASN mutation. 5 subjects were heterozygous at PRNP codon 129 and 2 were homozygous. The duration of die disease was longer in the heterozygotes. The distribution of histopathology showed a highly consistent pattern irrespectively of the codon 129 genotype. Spongiosis, astrocytic gliosis and neuronal loss were most marked in the cerebral cortex followed in decreasing order of severity by the striatum and thalamus. The cerebellum was normal or showed minimal focal spongiosis. The brainstem, hypothalamus and pallidus were spared. PrP immunocytochemistry revealed a granular pattern of immunoreactivity with small plaque-like aggregates in the cerebral cortex, striatum and, focally, in the molecular layer of the cerebellum. The size and the ratio of the differently glycosylated PrPres isoforms showed a consistent pattem and did not differ significantly between codon 129 homo- and heterozygotes. The topography of histopathology as well as the pattern of PrPres intracerebral deposition or electrophoretic mobility distinguished the CJD178 subtype from the sporadic CJD variants and from the familial CJD200 subtype. These findings further support the hypothesis that the phenotypic expression of human prion diseases is largely controlled by the PRNP genotype and by the characteristics of the PrPres fragment accumulating in the brain. Supported by AG-08l55. AG-08992 and the Britton Fund.
IN Von 7 Creutzfeldt-Jakob-Patienten mit einer Mutation von Lysin zu Asparaginsäure an Position 178 waren 5 bezüglich des Codons 129 heterozygot und nur 2 homozygot. Die Homozygoten erkrankten früher und die Krankheitsphase dauerte bei den Heterozygoten länger. Die räumlichen Muster der Neuronenauflösung und Astrozytose waren unabhängig vom Codon 129 in allen Fällen sehr ähnlich in der Hirnrinde am stärksten, im Striatum geringer und im Thalamus noch geringer. Die Kleinhirne waren kaum, Hypothalamus und Pallidum gar nicht betroffen. Immunologisch wurden kleine Aggregationen in der Hirnrinde, im Striatum und der molekularen Schicht des Kleinhirns gefunden. Auch die scheinbaren Molekularmassen und die Mengenverhältnisse der unterschiedlich stark glykosylierten Prionproteine waren in allen Fällen gleich. Diese Eigenschaften sind offenbar charakteristisch für diese 178-Asp-Mutation.
ZR 0
SP englisch
OR Prion-Krankheiten 6
ZF kritische Zusammenfassung des Meeting Abstracts von Roland Heynkes