NR AWKH
AU Mitrova,E.
TI Characterization of Creutzfeldt-Jakob disease with mutation E200K (CJDE200K) of Central European type
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions GEN-18
PT Konferenz-Poster
AB Creutzfeldt -Jakob disease (CJD) with the prion gene (PRNP) mutation E200K (CJDE200K) is the most common human genetic prion disease (gPD). It is randomly distributed worldwide and accumulated in geographic (Slovakia) and ethnic (Israel) clusters. Analysis in CJDE200K of different origin revealed Mediterranean, Japanese, Western European and Central European (CE) haplotypes. These types may differ in penetrance, transmissibility etc. CE haplotype shows the highest occurrence in Slovak CJDE200K clusters, causing in Slovakia the highest incidence (65%) of gPDs in Europe. Studied were: 183 definite CJD, 357 relatives of genetic CJD (gCJD) and 950 healthy corneal donors, histopathology, immunochemistry, genetic testing, epidemiology, genealogy. The mean CJD annual incidence in 1975-2005 was 1,45/mill (CJDE200K 0.88/mill, sporadic CJD (sCJD) 0.57/mill).CJDE200K represents 65% of all cases, 50.42% of which are familial.The mean age at onset in two generations differed (14.9 yrs) significantly. E200K mutation was found in 34.73 % of "healthy" relatives. Genetic testing of corneal donors revealed 2 asymptomatic carriers (AC). Penetrance of the E200K mutation is 59%. CJDE200K experimental transmission results resembled sCJD.The mutated allele co-segregates with methionine at codon 129. Distribution of M129V polymorphism in CJDE200K patients is MM 78.6%, MV 21.40%, in carriers MM 64%, MV 36%. Methionine homozygosity significantly reduced the disease duration. Genealogical studies showed a spread of CJDE200K to Hungary, Bohemia, Poland, also to Belgium, France, USA, Canada. Farmers are most represented in gCJD and even their percentage is decreasing, it is significantly higher than in employed population. CE type of E200K characterize: incomplete penetrance, transmissibility comparable to sCJD, 50% of familial pattern, generation gap at onset indicating anticipation, short clinical course in methionine homozygots. Data may serve for comparison to other subtypes of CJDE200K and as basis for future studies of genetic and exogenous (Cu/Mn, infection) factors, co-influencing manifestation of CJD in AC - the gCJD-risk group, which is at risk to develop and to transmit the disorder and at present the only one available for specific prevention of prion disease.
AD Eva J. Mitrová, Department of Prion Diseases, Slovak Medical University, Bratislava, Slovakia. E-mail: eva.mitrova@szu.sk
SP englisch
PO Italien