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.
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.
The spongiform encephalopathy Creutzfeldt-Jakob disease (CJD) has been transmitted to man via administration of growth hormone and gonadotropin extracted from large pooled batches of human cadaveric pituitary glands.
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.
These observations, together with data on published British patients with 11 and 14 repeats, strongly suggest that the occurrence of 10 or more octapeptide repeats in the encoded amyloid precursor protein predisposes to CJD.
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.