NR AXOZ
AU Ironside,J.W.; Bishop,M.; McCardle,L.; Ritchie,D.L.; Head,M.W.
TI PRNP Codon 129 Genotype and PrPres Isoform are Major Phenotypic Determinants in hGH Iatrogenic CJD Cases in the UK
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.131
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: Around 200 cases of iCJD have occurred since 1985 in recipients of hGH world-wide, yet little has been reported on the pathological phenotype of this disorder and its determinants. We present an analysis of 37 cases of iCJD in hGH recipients in the UK in whom pathological material was available for investigation.
Objectives: The aims of this study were to establish the pathological phenotype in UK hGH cases of iCJD, and to relate this to the PRNP codon 129 polymorphism and the PrPres isoform in the brain, which are known to be major pathological phenotypic determinants in sCJD.
Methods: Detailed neuropathological analysis and prion protein immunohistochemistry was performed on a series of 37 cases of hGH iCJD that were referred to the National CJD Surveillance Unit in the UK since 1991, which is the largest series of its type. In addition to histological analysis, the PrPres isoform was studied by Western blot analysis of frozen brain tissue whenever available, and the PRNP codon 129 polymorphism was analysed in DNA extracted from brain tissue or blood. Non-neural tissues were also analysed whenever available for the presence of PrPres and the results were compared to basic clinical data available at the time of autopsy.
Results: The cases were classified according to PRNP genotype as follows in 26/37 cases: 13 MV, 11 VV and 2 MM. PrPres isoform analysis in 20 of these cases found 7 VV2, 6 MV2, 3 MV1 and 1 MM1 cases. 3 cases had multiple PrPres isoforms present: 2 MV1+2 and 1 VV1+2. PRNP homozygosity did not predominate in this series, and the codon 129 polymorphism had a major bearing on disease duration (6.2 months for VV,
13.5 months for MV). The pathological phenotype resembled that of kuru, and varied according to the PRNP codon 129 polymorphism and PrPres isoform in the brain: for example, kuru-type plaques were confirmed to the MV2 subgroup. Conclusions: The pathological phenotype in iCJD in hGH recipients in UK has some similarities to kuru, and is substantially influenced by PRNP codon 129 genotype and brain PrPres isoform. The former also appears to influence the disease duration in these patients. The presence of PrPres type 1, type 2 and mixed isoforms suggest that more than one source of infection (presumably undiagnosed sCJD cases) may have been responsible for this outbreak.
AD J. Ironside, M. Bishop, L. McCardle, D. Ritchie, M. Head, University of Edinburgh, National CJD Surveillance Unit
SP englisch
PO Schottland
EA pdf-Datei und Poster (Posterautoren: J.W. Ironside, D.L. Ritchie, L. McCardle, C.A. McKenzie, J. Mackenzie, D. Everington und M.W. Head)