Comprehensive Neuropathologic Analysis of Genetic Prion Disease Associated With the E196K Mutation in PRNP Reveals Phenotypic Heterogeneity
2011 | journal article. A publication with affiliation to the University of Göttingen.
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Comprehensive Neuropathologic Analysis of Genetic Prion Disease Associated With the E196K Mutation in PRNP Reveals Phenotypic Heterogeneity
Eigenbrod, S.; Frick, P.; Giese, A.; Schelzke, G.; Zerr, I. & Kretzschmar, H. A. (2011)
Journal of Neuropathology and Experimental Neurology, 70(3) pp. 192-200. DOI: https://doi.org/10.1097/NEN.0b013e31820cd8a4
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- Authors
- Eigenbrod, Sabina; Frick, Petra; Giese, Armin; Schelzke, Gabi; Zerr, Inga; Kretzschmar, Hans A.
- Abstract
- The genetic forms of human transmissible spongiform encephalopathies (TSEs) are linked to mutations in the gene encoding the prion protein (PRNP) and account for 10% to 15% of human TSE cases. Some are distinct with respect to clinical signs, disease onset/duration, and diagnostic findings, whereas others closely resemble sporadic Creutzfeldt-Jakob disease (sCJD). We report a comprehensive analysis of 4 patients carrying the rare E196K (GAG -> AAG) mutation who presented with clinical features of CJD. To date, information on this PRNP mutation is limited to clinical and genetic data. Consequently, the E196K mutation could not be unequivocally assigned to human prion disease. We report histopathologic and biochemical findings in addition to clinical observations, thus providing a more comprehensive analysis of this presumably genetic prion disease. Our data indicate that (i) the E196K mutation is causally linked to human prion disease, (ii) there is a complex phenotypic spectrum of this mutation that includes nonspecific symptoms at onset and features typical of sCJD during disease progression, and (iii) the corresponding histologic picture comprises both cases with atypical neuropathology and cases that closely resemble subtypes of sCJD corresponding to the classification of Parchi et al, with subtle modifications in hippocampal regions CA1-4.
- Issue Date
- 2011
- Status
- published
- Publisher
- Lippincott Williams & Wilkins
- Journal
- Journal of Neuropathology and Experimental Neurology
- ISSN
- 0022-3069
- Sponsor
- Federal Ministry of Health (Bundesgesundheitsministerium) [1369-340]