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Research

Variant Creutzfeldt-Jakob disease: prion protein genotype analysis of positive appendix tissue samples from a retrospective prevalence study

BMJ 2006; 332 doi: https://doi.org/10.1136/bmj.38804.511644.55 (Published 18 May 2006) Cite this as: BMJ 2006;332:1186

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  1. James W Ironside, professor of clinical neuropathology (james.ironside{at}ed.ac.uk)1,
  2. Matthew T Bishop, geneticist1,
  3. Kelly Connolly, genetics technician1,
  4. Doha Hegazy, research technician2,
  5. Suzanne Lowrie, biomedical scientist1,
  6. Margaret Le Grice, biomedical scientist1,
  7. Diane L Ritchie, research assistant1,
  8. Linda M McCardle, biomedical scientist1,
  9. David A Hilton, consultant neuropathologist2
  1. 1 National Creutzfeldt-Jakob Disease Surveillance Unit, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU
  2. 2 Department of Histopathology, Derriford Hospital, Plymouth PL6 8DSH
  1. Correspondence to: J W Ironside

    Abstract

    Objective To perform prion protein gene (PRNP) codon 129 analysis in DNA extracted from appendix tissue samples that had tested positive for disease associated prion protein.

    Design Reanalysis of positive cases identified in a retrospective anonymised unlinked prevalence study of variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom.

    Study samples Three positive appendix tissue samples out of 12 674 samples of appendix and tonsil tested for disease associated prion protein. The patients from whom these samples were obtained were aged 20-29 years at the time of surgery, which took place in 1996-9.

    Setting Pathology departments in two tertiary centres in England and Scotland.

    Results Adequate DNA was available for analysis in two of the three specimens, both of which were homozygous for valine at codon 129 in the PRNP.

    Conclusions This is the first indication that the valine homozygous subgroup at codon 129 in the PRNP is susceptible to vCJD infection. All tested clinical cases of vCJD have so far occurred in the methionine homozygous subgroup, and a single case of probable iatrogenic vCJD infection has been identified in one patient who was a methionine/valine heterozygote at this genetic locus. People infected with vCJD with a valine homozygous codon 129 PRNP genotype may have a prolonged incubation period, during which horizontal spread of the infection could occur either from blood donations or from contaminated surgical instruments used on these individuals during the asymptomatic phase of the illness.

    Footnotes

    • Contributors JWI (guarantor) and DAH were responsible for the prevalence study and the analysis of the results, including the selection of the cases for analysis, and drafted and modified the manuscript. MTB established the methods for DNA extraction and analysis, designed and executed the validation study, and drafted and modified the manuscript. KC and DH performed the DNA extraction on the test materials and in the validation study and modified the manuscript. MLeG, SL, DLR, and LMcC identified cases for the validation study and prepared the paraffin sections for DNA analysis and modified the manuscript.

    • Funding The prevalence study was funded by the Department of Health (1216963 DAH; 1216982 JWI).

    • Competing interests None declared.

    • Ethical approval The prevalence study received approval from the South and West multi-centre research ethics committee (MREC reference 99/6/32) and for each of the centres included, appropriate local research ethics committee approval.

      Editorial by Wilson and Ricketts

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