Giuseppe
Emeritus
[Source: PLoS ONE, full text: (LINK). Abstract, edited.]
Human Prion Diseases in The Netherlands (1998?2009): Clinical, Genetic and Molecular Aspects
Casper Jansen<SUP>1</SUP><SUP>#</SUP><SUP>*</SUP>, Piero Parchi<SUP>2</SUP><SUP>#</SUP>, Sabina Capellari<SUP>2</SUP>, Carla A. Ibrahim-Verbaas<SUP>3</SUP><SUP>,</SUP><SUP>4</SUP>, Maaike Schuur<SUP>3</SUP>, Rosaria Strammiello<SUP>2</SUP>, Patrizia Corrado<SUP>2</SUP>, Matthew T. Bishop<SUP>5</SUP>, Willem A. van Gool<SUP>6</SUP>, Marcel M. Verbeek<SUP>7</SUP>, Frank Baas<SUP>6</SUP><SUP>,</SUP><SUP>8</SUP>, Wesley van Saane<SUP>1</SUP>, Wim G. M. Spliet<SUP>1</SUP>, Gerard H. Jansen<SUP>9</SUP>, Cornelia M. van Duijn<SUP>4</SUP>, Annemieke J. M. Rozemuller<SUP>1</SUP><SUP>,</SUP><SUP>10</SUP><SUP>,</SUP><SUP>11</SUP>
1 Dutch Surveillance Centre for Prion Diseases, University Medical Centre Utrecht, Utrecht, The Netherlands, 2 Istituto delle Scienze Neurologiche and Dipartimento di Scienze Neurologiche, Universit? di Bologna, Bologna, Italy, 3 Department of Neurology, Erasmus University Medical Centre, Rotterdam, The Netherlands, 4 Dutch National Prion Disease Registry, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands, 5 National Creutzfeldt-Jakob Disease Surveillance Unit, University of Edinburgh, Edinburgh, United Kingdom, 6 Department of Neurology, Academic Medical Centre, Amsterdam, The Netherlands, 7 Radboud University Nijmegen Medical Centre, Departments of Neurology and Laboratory Medicine, Donders Institute for Brain Cognition and Behavior, Alzheimer Centre Nijmegen, Nijmegen, The Netherlands, 8 Department of Genome Analysis, Academic Medical Centre, Amsterdam, The Netherlands, 9 Creutzfeldt-Jakob Disease Surveillance System, Prion Diseases Program, Public Health Agency of Canada, Ottawa, Ontario, Canada, 10 Netherlands Brain Bank, Amsterdam, The Netherlands, 11 Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
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 PrP<SUP>Sc</SUP> 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.
Citation: Jansen C, Parchi P, Capellari S, Ibrahim-Verbaas CA, Schuur M, et al. (2012) Human Prion Diseases in The Netherlands (1998?2009): Clinical, Genetic and Molecular Aspects. PLoS ONE 7(4): e36333. doi:10.1371/journal.pone.0036333
Editor: Mathias Toft, Oslo University Hospital, Norway
Received: December 2, 2011; Accepted: April 1, 2012; Published: April 30, 2012
Copyright: ? 2012 Jansen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors have no support or funding to report.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: c.jansen@umcutrecht.nl
# These authors contributed equally to this work.
- ------Casper Jansen<SUP>1</SUP><SUP>#</SUP><SUP>*</SUP>, Piero Parchi<SUP>2</SUP><SUP>#</SUP>, Sabina Capellari<SUP>2</SUP>, Carla A. Ibrahim-Verbaas<SUP>3</SUP><SUP>,</SUP><SUP>4</SUP>, Maaike Schuur<SUP>3</SUP>, Rosaria Strammiello<SUP>2</SUP>, Patrizia Corrado<SUP>2</SUP>, Matthew T. Bishop<SUP>5</SUP>, Willem A. van Gool<SUP>6</SUP>, Marcel M. Verbeek<SUP>7</SUP>, Frank Baas<SUP>6</SUP><SUP>,</SUP><SUP>8</SUP>, Wesley van Saane<SUP>1</SUP>, Wim G. M. Spliet<SUP>1</SUP>, Gerard H. Jansen<SUP>9</SUP>, Cornelia M. van Duijn<SUP>4</SUP>, Annemieke J. M. Rozemuller<SUP>1</SUP><SUP>,</SUP><SUP>10</SUP><SUP>,</SUP><SUP>11</SUP>
1 Dutch Surveillance Centre for Prion Diseases, University Medical Centre Utrecht, Utrecht, The Netherlands, 2 Istituto delle Scienze Neurologiche and Dipartimento di Scienze Neurologiche, Universit? di Bologna, Bologna, Italy, 3 Department of Neurology, Erasmus University Medical Centre, Rotterdam, The Netherlands, 4 Dutch National Prion Disease Registry, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands, 5 National Creutzfeldt-Jakob Disease Surveillance Unit, University of Edinburgh, Edinburgh, United Kingdom, 6 Department of Neurology, Academic Medical Centre, Amsterdam, The Netherlands, 7 Radboud University Nijmegen Medical Centre, Departments of Neurology and Laboratory Medicine, Donders Institute for Brain Cognition and Behavior, Alzheimer Centre Nijmegen, Nijmegen, The Netherlands, 8 Department of Genome Analysis, Academic Medical Centre, Amsterdam, The Netherlands, 9 Creutzfeldt-Jakob Disease Surveillance System, Prion Diseases Program, Public Health Agency of Canada, Ottawa, Ontario, Canada, 10 Netherlands Brain Bank, Amsterdam, The Netherlands, 11 Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
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 PrP<SUP>Sc</SUP> 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.
Citation: Jansen C, Parchi P, Capellari S, Ibrahim-Verbaas CA, Schuur M, et al. (2012) Human Prion Diseases in The Netherlands (1998?2009): Clinical, Genetic and Molecular Aspects. PLoS ONE 7(4): e36333. doi:10.1371/journal.pone.0036333
Editor: Mathias Toft, Oslo University Hospital, Norway
Received: December 2, 2011; Accepted: April 1, 2012; Published: April 30, 2012
Copyright: ? 2012 Jansen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors have no support or funding to report.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: c.jansen@umcutrecht.nl
# These authors contributed equally to this work.