NR ABVJ
AU Brown,P.; Goldfarb,L.G.; Gibbs,C.J.Jr.; Gajdusek,D.C.
TI The phenotypic expression of different mutations in transmissible familial Creutzfeldt-Jakob disease
QU European Journal of Epidemiology 1991 Sep; 7(5): 469-76
PT journal article
AB Cases of familial Creutzfeldt-Jakob disease (CJD) with mutations in the PRNP gene were analyzed for distinctive clinico-pathological and experimental transmission characteristics. An insert mutation within the region of codons 51 to 91 was associated with a markedly early age at onset and prolonged course of illness. Point mutations at codons 178 and 200 were also associated with ages at onset, durations of illness, and clinical symptom profiles that differed from sporadic CJD. The age at onset of illness in each group was correlated with the length of incubation periods in primates inoculated with their brain tissue, suggesting that the early onset of familial CJD results not from a time shift of the initiating event, but from an accelerated pre-clinical (incubation) phase of disease, perhaps due to a more rapid formation of amyloid induced by a mutationally-altered precursor protein template.
IN Die Art der Mutation des Prionproteins beeinflußt die Inkubationszeit und die Symptome. Mit Hirnmaterial von familiären und sporadischen Creutzfeldt-Jakob-Fällen gelang den Autoren die intrazerebrale Übertragung auf Totenkopfäffchen (Saimiri sciureus, squirrel monkey). Hirnhomogenat von Patienten mit erblicher Creutzfeldt-Jakob-Krankheit ließ außerdem Kapuzineraffen (Cebus capucinus, Capuchin monkey), Klammeraffen (Ateles x, Spider monkey), Schimpansen (Pan troglodytes, Chimpanzee), Rhesus-Affen (Macaca mulatta, Rhesus monkey) und grüne Meerkatze (Cercopithecus aethiops, African green monkey) erkranken. Nach einer Übertragung auf Affen waren die Inkubationszeiten der Affen umso kürzer, je jünger die "Spenderpatienten" gestorben waren.
MH Adult; Aged; Animal; Brain/microbiology/pathology; Codon; Creutzfeldt-Jakob Syndrome/*genetics/pathology/transmission; DNA, Viral/analysis; Gene Expression; Human; Macaca; Middle Age; *Mutation; Phenotype; Polymerase Chain Reaction; PrPc Proteins; Primates; Prions/*genetics; Protein Precursors/*genetics
AD Paul Brown (pwb@codon.nih.gov), Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
SP englisch
PO Italien
OR Prion-Krankheiten 2