Protease-resistant PrP was found in both patients with fatal familial insomnia, but the size and number of protease-resistant fragments differed from those in Creutzfeldt-Jakob disease.
A group of 43 patients from seven families affected by Creutzfeldt-Jakob disease (CJD) with the codon 178Asn mutation of the PRNP amyloid precursor gene is compared to a group of 211 patients with the sporadic form of the disease.
We describe 2 patients of Jewish Libyan descent, who presented with a clinical syndrome compatible with Creutzfeldt-Jakob disease and who were found to have a mutation of codon 200 in the prion protein.
Fatal familial insomnia (FFI) and a subtype of familial Creutzfeldt-Jakob disease (CJD), two clinically and pathologically distinct diseases, are linked to the same mutation at codon 178 (Asn178) of the prion protein gene.
Examination of the prion protein genes of all these cases and of a single case of gonadotropin-related CJD showed that 4 had the uncommon valine 129 homozygous genotype indicating genetic susceptibility to prion infection.
Despite their experimental transmissibility, missense and insertional mutations in the prion protein gene are associated with both GSS and familial CJD, demonstrating that the human familial cases are autosomal dominant diseases.
Creutzfeld-Jacob disease and Gerstmann-Sträussler syndrome are rare degenerative disorders of the nervous system which have been genetically linked to the prion protein (PrP) gene.
The PRNP gene, encoding the amyloid precursor protein that is centrally involved in Creutzfeldt-Jakob disease (CJD), has an unstable region of five variant tandem octapeptide coding repeats between codons 51 and 91.
Cases of familial Creutzfeldt-Jakob disease (CJD) with mutations in the PRNP gene were analyzed for distinctive clinico-pathological and experimental transmission characteristics.
Molecular genetic studies disclosed a new G-to-A mutation in codon 178 of the PRNP gene (resulting in a substitution of asparagine for aspartic acid) in the DNA of eight family members with CJD but not in any of ten currently healthy first degree relatives of the patients, or 86 controls.
Analysis of this and other families with similar inserts suggests that such mutations in the PRNP gene not only predispose to CJD, but also modify its phenotypic expression.
In the prion protein genotype analysis of other patients with CJD, the Leu102 allele was revealed to be carried heterozygously by 6 of 7 patients who had CJD with congophilic kuru plaques, yet no patient with CJD without congophilic kuru plaques had this allele.
The polymerase chain reaction was used to screen DNA samples from 12 unrelated individuals with various familial dementias and ataxias for mutation in part of the prion protein (PrP) gene, an abnormality that occurs in individuals with the spongiform encephalopathies, Gerstmann-Sträussler syndrome (GSS) and Creutzfeldt-Jakob disease.
The prion protein (PrP) is found in amyloid of animals with scrapie and humans with Creutzfeldt-Jakob disease; the beta protein is present in amyloid deposits in Alzheimer disease and Down syndrome patients.
In the present paper a family from an areal focal accumulation of CJD in Central Slovakia with 1 histopathologically verified case of Creutzfeldt-Jakob disease and 2 case of retinitis pigmentosa is described.
In keeping with findings of previous studies using other lines of PrP-less mice inoculated with scrapie agents, no PrP-/- mice showed any sign of the disease for 460 days after inoculation, while all of the PrP+/- and control PrP+/+ mice developed CJD-like symptoms and died.
We found a significant correlation between valine at codon 129 of the prion protein gene and the presence of plaque in CJD and a later age of onset in CJD cases possessing the Apo E2 allele.