Human prion diseases in the Netherlands (1998-2009): Clinical, genetic and molecular aspects

Casper Jansen, Piero Parchi, Sabina Capellari, Carla A. Ibrahim-Verbaas, Maaike Schuur, Rosaria Strammiello, Patrizia Corrado, Matthew T. Bishop, Willem A. van Gool, Marcel M. Verbeek, Frank Baas, Wesley van Saane, Wim G M Spliet, Gerard H. Jansen, Cornelia M. van Duijn, Annemieke J M Rozemuller

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Abstract

Prion diseases are rare and fatal neurodegenerative disorders that can be sporadic, inherited or acquired by infection. Based on a national surveillance program in the Netherlands we describe here the clinical, neuropathological, genetic and molecular characteristics of 162 patients with neuropathologically confirmed prion disease over a 12-year period (1998-2009). Since 1998, there has been a relatively stable mortality of Creutzfeldt-Jakob disease (CJD) in the Netherlands, ranging from 0.63 to 1.53 per million inhabitants per annum. Genetic analysis of the codon 129 methionine/valine (M/V) polymorphism in all patients with sporadic CJD (sCJD) showed a trend for under-representation of VV cases (7.0%), compared with sCJD cohorts in other Western countries, whereas the MV genotype was relatively over-represented (22,4%). Combined PrPSc and histopathological typing identified all sCJD subtypes known to date, except for the VV1 subtype. In particular, a "pure" phenotype was demonstrated in 60.1% of patients, whereas a mixed phenotype was detected in 39.9% of all sCJD cases. The relative excess of MV cases was largely accounted for by a relatively high incidence of the MV 2K subtype. Genetic analysis of the prion protein gene (PRNP) was performed in 161 patients and showed a mutation in 9 of them (5.6%), including one FFI and four GSS cases. Iatrogenic CJD was a rare phenomenon (3.1%), mainly associated with dura mater grafts. Three patients were diagnosed with new variant CJD (1.9%) and one with variably protease-sensitive prionopathy (VPSPr). Post-mortem examination revealed an alternative diagnosis in 156 patients, most commonly Alzheimer's disease (21.2%) or vascular causes of dementia (19.9%). The mortality rates of sCJD in the Netherlands are similar to those in other European countries, whereas iatrogenic and genetic cases are relatively rare. The unusual incidence of the VV2 sCJD subtype compared to that reported to date in other Western countries deserves further investigation.

Original languageEnglish
Article numbere36333
JournalPLoS One
Volume7
Issue number4
DOIs
Publication statusPublished - Apr 30 2012

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Jansen, C., Parchi, P., Capellari, S., Ibrahim-Verbaas, C. A., Schuur, M., Strammiello, R., Corrado, P., Bishop, M. T., van Gool, W. A., Verbeek, M. M., Baas, F., van Saane, W., Spliet, W. G. M., Jansen, G. H., van Duijn, C. M., & Rozemuller, A. J. M. (2012). Human prion diseases in the Netherlands (1998-2009): Clinical, genetic and molecular aspects. PLoS One, 7(4), [e36333]. https://doi.org/10.1371/journal.pone.0036333