NR AOXZ
AU Poulter,M.; Beck,J.A.; Campbell,T.A.; Uphill,J.B.; Adamson,G.; Mead,S.; Collinge,J.
TI Small Pool PCR to test for somatic octapeptide repeat variation in sporadic CJD patients
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - DG-65
PT Konferenz-Poster
AB The aetiology of human prion diseases can be inherited, sporadic or acquired. Inherited cases constitute ~15% of cases and acquired cases (Kuru, iatrogenic and vCJD) are rare although the extent of any epidemic resulting from consumption of BSE contaminated meat is still difficult to quantify. At present most human cases are sporadic. The hypothesis that sCJD cases arise as a result of exposure to an environmental source of prions is not supported by epidemiological evidence and the exact aetiology remains obscure and may well be heterogeneous. Genetic variation in addition to codon 129 genotype may be a susceptibility factor. It has been postulated that sCJD could arise due to somatic mutation within the PrP gene ORF resulting in cells producing protein predisposed to alter conformation and spontaneously convert to PrPsc. Somatic mutation may involve only a small proportion of cells in a susceptible cell type such as neurones which could remain undetected by the usual techniques used to identify germ line mutations. These mutations are likely to occur non-randomly at mutation hotspots within the ORF of the PrP gene. The most likely location for such a hotspot is the octapeptide repeat region where octapeptide repeat insertions (OPRI) account for 50% of all pathogenic mutations characterised to date. OPRI are also more favoured candidates due to the ability of germline OPRI cases to transmit to mice more readily than point mutation cases in the same way that sCJD cases do. In addition, molecular and biological strain typing studies show a close similarity between prion strains seen in sCJD and germline OPRI cases. We have used small pool PCR (sp-PCR) to screen 60,000 genomes for each of 15 brain samples from sCJD patients for evidence of somatic octapeptide repeat insertions (OPRI) variants. No clear evidence was found to support somatic mutation of the octapeptide repeat region of PRNP as a possible aetiology of sCJD.
AD M. Poulter, J.A. Beck, T.A. Campbell, J.B. Uphill, G. Adamson, S. Mead, J. Collinge, MRC Prion Unit, UK
SP englisch
PO Deutschland