• Online Features  This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on Web of Science (3)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Neurology  • Neurogenetics  • Prion Diseases  • Genetic Disorders  • Alert me on articles by topic  Social Bookmarking   What's this?

Ana Lukic, MD, MRCP; Jonathan Beck, BSc; Susan Joiner, BSc; Julian Fearnley, FRCP; Steve Sturman, FRCP; Sebastian Brandner, FRCP; Jonathan D. F. Wadsworth, PhD; John Collinge, FRS; Simon Mead, PhD, MRCP

Arch Neurol. 2010;67(8):1021-1023. doi:10.1001/archneurol.2010.184

Background  Genetic variants of the prion protein gene (PRNP) strongly determine susceptibility to prion diseases. All tested patients with definite variant Creutzfeldt-Jakob disease (vCJD) are homozygous for methionine at a common polymorphism at codon 129. A further genetic polymorphism at codon 219, a common variant in several Asian populations, is considered protective against sporadic CJD.

Objective  To report a finding of heterozygosity at codon 219 in 2 patients with vCJD.

Design  Case reports.

Setting  MRC (Medical Research Council) Prion Unit and Department of Neurodegenerative Disease, University College London Institute of Neurology, and National Prion Clinic, National Hospital for Neurology and Neurosurgery.

Patients  Two patients with clinical and investigation findings consistent with the diagnoses of probable vCJD.

Main Outcome Measures  Clinical and genetic findings.

Results  A 34-year-old man had a 15-month history of behavioral change progressing to ataxia, dysarthria, involuntary choreiform movements, and severe cognitive impairment. Cerebrospinal fluid analysis was positive for 14-3-3 protein, electroencephalography showed generalized slowing, and magnetic resonance imaging revealed thalamic high signal bilaterally, typical of vCJD. A 31-year-old woman had a 16-month history of cognitive decline, ataxia, involuntary choreiform movements, and myoclonic jerks. Magnetic resonance imaging showed bilateral pulvinar high signal. The diagnosis was confirmed by a tonsillar biopsy demonstrating abnormal prion protein deposition in a typical pattern for vCJD. PRNP sequencing showed a methionine homozygous codon 129 genotype and an E219K polymorphism in both patients.

Conclusions  The E219K polymorphism is neutral or may even confer susceptibility to vCJD. The observations are interpretable in the context of the conformational selection model of prion replication. A barrier to prion disease transmission depends on the degree to which permitted pathologic conformations of the prion protein overlap between the inoculum and the host.

Author Affiliations: MRC (Medical Research Council) Prion Unit (Drs Lukic, Wadsworth, Collinge, and Mead; Mr Beck; and Ms Joiner) and Department of Neurodegenerative Disease (Drs Brandner, Collinge, and Mead), University College London Institute of Neurology, London; National Prion Clinic, National Hospital for Neurology and Neurosurgery, London (Drs Lukic, Collinge, and Mead); The Barts and Royal London Hospital National Health Service Trust, London (Dr Fearnley); and Queen Elizabeth Neuroscience Unit, University Hospital Birmingham National Health Service Trust, Birmingham (Dr Sturman), United Kingdom.

CiteULike    Connotea    Delicious    Digg    Facebook    Reddit    Technorati    Twitter     What's this?