No differences between our dura-CJD cases and typical cases of sporadic CJD were found with respect to clinicopathologic findings, except history of dura mater transplantation.
We identified two different rare mutations in codon 188 of the prion protein gene (PRNP) in four patients suffering from a disease clinically very similar to the major subtype of sporadic CJD.
We have compared clinicpathological patient profiles including geographic and gender distribution, age at disease onset, duration of disease, clinical symptoms, and recognized or hypothetical risk factors for CJD, genetic risk factors, biochemical and histopathological data for two cohorts of Swiss sporadic CJD patients from years of regular sporadic CJD incidence (1996-2000, mean incidence 1.3 cases/10(6) inhabitants, n = 47) to Swiss sporadic CJD patients from years of elevated sporadic CJD incidence (2001-2004, mean incidence 2.3 cases/10(6) inhabitants, n = 73).
In order to investigate whether single nucleotide polymorphisms within regulatory region of PRNP may modulate genetic susceptibility to sporadic CJD we examined an association of the C/G polymorphism at position -101 with the sCJD.
These results support a clinicopathologic classification system whereby both PrPres type and codon 129 genotype are utilized to most accurately depict phenotypic subtypes or strains of sporadic CJD.
Despite the clinical diversity and atypical laboratory findings seen in familial CJD with the codon 200 mutation, these neuroimaging studies suggest that common regional distributions and a common pathogenesis might underlie the clinical progression both in sporadic CJD and in familial CJD with the codon 200 mutation in the prion protein gene.
Western blot analysis of PrP(Sc) in the brain in vCJD tissue shows a uniform isotype, with a glycoform ratio characterized by predominance of the diglycosylated band, distinct from sporadic CJD.
Furthermore, polymorphic codon 129 of the PRNP gene encodes either methionine or valine and appears to influence the susceptibility of patients to iatrogenic and sporadic CJD as well as the neuropathological phenotype in these forms of CJD.
Based on the genotype at codon 129 on both PRNP alleles, the size of protease resistant PrP(Sc) fragments and disease phenotype, we divide sporadic CJD into six subtypes: sCJDMM1/sCJDMV1, sCJDVV2, sCJDMV2, sCJDMM2, sCJDVV1, and sporadic fatal insomnia (sFI).
This patient is the first case of sporadic CJD with plaque-forming MM1-type PrP, suggesting either a shared prion strain with the plaque-forming subset of dural graft-associated CJD or shared host genetic factors that are unrelated to the PrP genotype.
The pattern of PrP(Sc) deposition in the brains of Tg mice was similar to that caused by sCJD but different from that associated with fCJD(E200K) or FFI.
We analysed PrP27-30 glycotypes in a large number of TSE-affected patients: 50 sporadic CJD (sCJD), 1 iatrogenic CJD, 1 Gerstmann-Sträussler-Scheinker syndrome (GSS) with the Pro102Leu mutation of PrP, 3 familial CJD (fCJD) with the Glu200Lys mutation and, for the first time, 7 fCJD with the Val210ll3e mutation.
Our finding suggests that type A PrPres isoform is specifically found in the patients with GSS carrying codon 102 mutation, and there are at least two different PrPres isoforms in the patients with sporadic CJD.
In most cases of sporadic CJD immunohistochemistry for PrP shows widespread granular deposits of the scrapie isoform of the prion protein (PrPSc) in the cerebellar cortex.
Within the group of sporadic CJD patients (lacking PRNP mutations), we confirmed that the genotype distribution with respect to the common methionine/valine (Met/Val) polymorphism at codon 129 within PRNP was significantly different from the normal Caucasian population.
The appearance of spontaneous neurodegeneration in PrP transgenic mice carrying a human mutation has raised the possibility that the origin of sporadic CJD is solely genetic.
The sensitivity values of RT-QuIC for the diagnosis of sCJD are comparable or higher than those of the other tests (EEG, MRI, detection of 14-3-3 or tau proteins in cerebrospinal fluid) but with a specificity close to 100%.
The accessory examinations of magnetic resonance imaging (MRI), electroencephalography (EEG), 14-3-3 protein in cerebrospinal fluid and S100 protein in serum support the diagnosis of sporadic CJD (sCJD).