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Volume 20, Number 12—December 2014
Research

Variably Protease-Sensitive Prionopathy, a Unique Prion Variant with Inefficient Transmission Properties

Abigail B. Diack1, Diane Ritchie1, Alexander H. Peden, Deborah Brown, Aileen Boyle, Laura Morabito, David Maclennan, Paul Burgoyne, Casper Jansen, Richard S. Knight, Pedro Piccardo, James W. Ironside1, and Jean C. Manson1Comments to Author 
Author affiliations: The Roslin Institute, University of Edinburgh, Easter Bush, Scotland, UK (A.B. Diack, D. Brown, A, Boyle, L. Morabito, D. Maclennan, P. Burgoyne, J.C. Manson); School of Clinical Sciences, University of Edinburgh, Edinburgh, Scotland, UK (D.L. Ritchie, A.H. Peden, R.S. Knight, J.W. Ironside); Food and Drug Administration, Rockville, Maryland, USA (P. Piccardo); University Medical Centre Utrecht, Utrecht, the Netherlands (C. Jansen)

Main Article

Table 1

Characteristics of patients with variably protease-sensitive prionopathy whose brain samples were selected for transmission studies*

Patient, sex
 Age at death, y
 Disease duration, mo
 Clinical signs and symptoms
 Neuropathologic features
 PrPres type
NL-VV, M†
 57
 20
 Progressive dementia, spastic paraplegia, sensorimotor polyneuropathy
 Mild to moderate spongiform change in basal ganglia, and cerebral and cerebellar cortices. Coarse granular deposits of PrP in cerebral cortex, basal ganglia, and thalamus. PrP microplaques present within molecular layer of cerebellar cortex
 Faint ladder-like appearance of protease-resistant fragments with a prominent low–molecular weight fragment
UK-VV, F‡
 59
 42
 Progressive dementia, emotional and obsessive behavior (early), very occasional myoclonus (late)
 Mild to moderate spongiform change in basal ganglia, thalamus, and cerebral and cerebellar cortices. Widespread granular accumulations of PrP in all brain regions. PrP microplaques present within molecular layer of cerebellar cortex
 Faint, ladder-like appearance of protease-resistant fragments with a prominent low–molecular weight fragment
UK-MV, M§ 76 12 Forgetfulness, visuospatial perceptual problems, difficulties walking, action tremor, akinetic mutism Spongiform change most prominent in the frontal cortex. PrP microplaques, synaptic and granular accumulations of PrP restricted to cerebral cortex, basal ganglia, and thalamus. Diffuse Lewy body and tau pathology observed, with
amyloid-β plaques and a widespread amyloid angiopathy Faint ladder-like appearance of protease-resistant fragments including a low–molecular weight fragment

*PrP, prion protein; PrPres, protease-resistant isoform of the disease-specific PrP.
†NL-VV, patient from the Netherlands who was homozygous for valine at codon 129 of the PrP gene (PRNP). Case report, Jansen et al. (6).
‡UK-VV, patient from the United Kingdom who was homozygous for valine at PRNP codon 129. Case report, Head et al. (5).
§UK-MV, patient from the United Kingdom who was heterozygous for methionine/valine at PRNP codon 129. Case report, Head et al. (17).

Main Article

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Main Article

1These authors contributed equally to this article.

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Page updated: November 18, 2014
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