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Published in: Acta Neuropathologica 5/2005

01-11-2005 | Case Report

Prion disease with a 144 base pair insertion: unusual cerebellar prion protein immunoreactivity

Authors: Ellen Gelpi, Gabor G. Kovacs, Thomas Ströbel, Oskar Koperek, Till Voigtländer, Pawel P. Liberski, Herbert Budka

Published in: Acta Neuropathologica | Issue 5/2005

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Abstract

Sporadic, acquired, and genetic human prion diseases are characterized neuropathologically by distinct deposition patterns of the abnormal, disease-associated form of the prion protein (PrPsc). In addition to mutations in the prion protein gene (PRNP), PrPsc immunostaining patterns correlate with molecular phenotypes of prion diseases defined by the PRNP polymorphism at codon 129 and with protease-resistant PrP classified by Western blotting. Some point or insertional PRNP mutations share similar clinical and neuropathological phenotypes, whereas others show great variability even within the same family. Here we report a patient who presented clinically as sporadic Creutzfeldt-Jakob disease (CJD). Histologically moderate spongiform change was seen in cerebral and cerebellar cortical areas. Neuronal loss was restricted mainly to the occipital cortex and the basal ganglia. Surprisingly, numerous eosinophilic globular structures were noted in the molecular layer and the parahippocampal gyrus. These globules showed intense PrP immunopositivity using anti-PrP antibodies against different epitopes. They were stained with PAS but lacked congophilia and birefringence in polarized light. Ultrastructurally, globules were composed of 21-nm-thick intermingled filaments without dense core. Genetic analysis revealed a PRNP 144 base pair insertion. Our case reinforces the importance of molecular genetic diagnosis, especially in those patients who lack a family history of prion disease and show unusual neuropathological changes. It also widens the phenotypic spectrum of prion diseases. The phenotypic variability within the same mutation suggests further, yet uncharacterized, genetic or epigenetic influence on phenotype in these diseases.
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Metadata
Title
Prion disease with a 144 base pair insertion: unusual cerebellar prion protein immunoreactivity
Authors
Ellen Gelpi
Gabor G. Kovacs
Thomas Ströbel
Oskar Koperek
Till Voigtländer
Pawel P. Liberski
Herbert Budka
Publication date
01-11-2005
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 5/2005
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-005-1073-x

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