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Simon Mead, PhD, MRCP; Susan Joiner, MSc; Melanie Desbruslais, BSc; Jonathan A. Beck, BSc; Michael O’Donoghue, PhD; Peter Lantos, FRCP; Jonathan D. F. Wadsworth, PhD; John Collinge, FRS

Arch Neurol. 2007;64(12):1780-1784.

Background  Variant Creutzfeldt-Jakob disease (vCJD) is an acquired prion disease causally related to bovine spongiform encephalopathy that has occurred predominantly in young adults. All clinical cases studied have been methionine homozygotes at codon 129 of the prion protein gene (PRNP) with distinctive neuropathological findings and molecular strain type (PrP^Sc type 4). Modeling studies in transgenic mice suggest that other PRNP genotypes will also be susceptible to infection with bovine spongiform encephalopathy prions but may develop distinctive phenotypes.

Objective  To describe the histopathologic and molecular investigation in a young British woman with atypical sporadic CJD and valine homozygosity at PRNP codon 129.

Design  Case report, autopsy, and molecular analysis.

Setting  Specialist neurology referral center, together with the laboratory services of the MRC [Medical Research Council] Prion Unit.

Subject  Single hospitalized patient.

Main Outcome Measures  Autopsy findings and molecular investigation results.

Results  Autopsy findings were atypical of sporadic CJD, with marked gray and white matter degeneration and widespread prion protein (PrP) deposition. Lymphoreticular tissue was not available for analysis. Molecular analysis of PrP^Sc (the scrapie isoform of PrP) from cerebellar tissue demonstrated a novel PrP^Sc type similar to that seen in vCJD (PrP^Sc type 4). However, this could be distinguished from the typical vCJD pattern by an altered protease cleavage site in the presence of the metal ion chelator EDTA.

Conclusions  Further studies will be required to characterize the prion strain seen in this patient and to investigate its etiologic relationship with bovine spongiform encephalopathy. This case illustrates the importance of molecular analysis of prion disease, including the use of EDTA to investigate the metal dependence of protease cleavage patterns of PrP^Sc.

Author Affiliations: MRC [Medical Research Council] Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, London, England (Drs Mead, Wadsworth, and Collinge; Mss Joiner and Desbruslais; and Mr Beck); and Institute of Psychiatry, King's College London (Dr Lantos). Dr O’Donoghue is now with the Department of Clinical Neurology, Nottingham University Hospitals NHS [National Health Service] Trust, Nottingham, England.

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