NR ABVG
AU Brown,P.; Goldfarb,L.G.; McCombie,W.R.; Nieto,A.; Squillacote,D.; Sheremata,W.; Little,B.W.; Godec,M.S.; Gibbs,C.J.Jr.; Gajdusek,D.C.
TI Atypical Creutzfeldt-Jakob disease in an American family with an insert mutation in the PRNP amyloid precursor gene
QU Neurology 1992 Feb; 42(2): 422-7
PT journal article
AB An American family of English origin with an unusually early onset and long-duration form of Creutzfeldt-Jakob disease (CJD) had a heterozygous insert mutation in the region of repeating octapeptide coding sequences between codons 51 and 91 of the PRNP gene on chromosome 20. Affected members were 23 to 35 years old at the onset of illnesses that lasted from 4 to 13 years, yet experimental transmission of disease from the proband (11-year duration) produced a typically brief incubation period and duration of illness in each of three inoculated primates. Also, the PrP amyloid protein that accumulates in CJD brain was only barely detectable in extracted brain tissue from one case with massive spongiform change and was undetectable in another case with no spongiform change, perhaps because of epitope shielding by a configurational change in the protein induced by the mutation. 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 Bei einer amerikanischen Familie englischer Abstammung beginnen die Symptome der Creutzfeldt-Jakob-Krankheit mit 23-35 Jahren ungewöhnlich früh und das Leiden zieht sich mit 4-13 Jahren besonders lange hin. Die Familie ist durch eine Insertion in der Region der Oktapeptidwiderholungen zwischen den Codons 51 und 91 in einem der beiden Gene für das Prionprotein auf dem Chromosom 20 gekennzeichnet. Gehirnhomogenat eines Patienten übertrug die Krankheit mit kurzer Inkubationszeit auf 3 Affen.
MH Adult; Amino Acid Sequence; Amyloid beta-Protein Precursor/*genetics; Animal; Base Sequence; Blotting, Western; Brain/pathology; Case Report; Cebus; Creutzfeldt-Jakob Syndrome/*genetics/pathology/transmission; Female; Human; Male; Molecular Sequence Data; Mutation/*genetics; Pan troglodytes; Pedigree; Saimiri; United States
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 USA