NR AIND
AU Monari,L.; Chen,S.G.; Brown,P.; Parchi,P.; Petersen,R.B.; Mikol,J.; Gray,F.; Cortelli,P.; Montagna,P.; Ghetti,B.; Goldfarb,L.G.; Gajdusek,D.C.; Lugaresi,E.; Gambetti,P.; Autilio-Gambetti,L.
TI Fatal familial insomnia and familial Creutzfeldt-Jakob disease: different prion proteins determined by a DNA polymorphism.
QU Proceedings of the National Academy of Sciences of the United States of America 1994 Mar 29; 91(7): 2839-42
PT journal article
AB Fatal familial insomnia and a subtype of Creutzfeldt-Jakob disease, two clinically and pathologically distinct diseases, are linked to the same mutation at codon 178 (Asp-178 ->Asn) but segregate with different genotypes determined by this mutation and the methionine-valine polymorphism at codon 129 of the prion protein gene. The abnormal isoforms of the prion protein in these two diseases were found to differ both in the relative abundance of glycosylated forms and in the size of the protease-resistant fragments. The size difference was consistent with a different protease cleavage site, suggesting a different conformation of the protease-resistant prion protein present in the two diseases. These differences are likely to be responsible for the type and location of the lesions that characterize these two diseases. Therefore, the combination of the mutation at codon 178 and the polymorphism at codon 129 determines the disease phenotype by producing two altered conformations of the prion protein.
IN Die fatale erbliche Schlaflosigkeit und ein erblicher Subtyp der Creutzfeldt-Jakob-Krankheit entstehen beide durch die Mutation der Aminosäure 178 des Prionproteins von Asparaginsäure zu Asparagin. Die Krankheitsbilder unterscheiden sich, weil sich die Kranken hinsichtlich der polymorphen Aminosäure129 des selben Prionproteins unterscheiden. An dieser Position kann entweder ein Methionin oder ein Valin stehen. Dieser Unterschied führt zu Prionproteinen mit unterschiedlichen Zuckerketten, die durch Proteasen in verschieden große und wahrscheinlich auch verschieden gefaltete Fragmente zerlegt werden. Diese Unterschiede scheinen den Unterschieden der beiden Krankheiten zugrunde zu liegen.
MH Codon; Comparative Study; Creutzfeldt-Jakob Syndrome/*genetics; Endopeptidase K; Human; Peptide Fragments/chemistry; Phenotype; *Polymorphism (Genetics); PrPsc Proteins; Prion Diseases/*genetics; Prions/chemistry/drug effects/*genetics; Serine Endopeptidases/metabolism; Sleep Initiation and Maintenance Disorders/*genetics; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Division of Neuropathology, Case Western Reserve University, Cleveland, OH 44106.
SP englisch
PO USA