Atypical Creutzfeldt-Jakob disease in an American family with an insert mutation in the PRNP amyloid precursor gene

Brown, P., Goldfarb, L. G., McCombie, W. R., Nieto, A., Squillacote, D., Sheremata, W., Little, B. W., Godec, M. S., Gibbs Jr, C. J., Gajdusek, D. C. (1992) Atypical Creutzfeldt-Jakob disease in an American family with an insert mutation in the PRNP amyloid precursor gene. Neurology, 42 (2). pp. 422-427. ISSN 00283878 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/1736177
DOI: 10.1212/WNL.42.2.422

Abstract

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.

Item Type: Paper
Uncontrolled Keywords: amyloid protein octapeptide protein precursor adult animal model article brain spongiosis case report chromosome 20 creutzfeldt jakob disease disease transmission family female gene insertion gene mutation human human tissue nonhuman onset age primate priority journal united states Amino Acid Sequence Amyloid beta-Protein Precursor Animal Base Sequence Blotting, Western Brain Cebus Creutzfeldt-Jakob Syndrome Male Molecular Sequence Data Mutation Pan troglodytes Pedigree Saimiri
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
diseases & disorders > mental disorders > genetic disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
CSHL Authors:
Communities: CSHL labs > McCombie lab
Depositing User: Matt Covey
Date Deposited: 25 Apr 2013 20:19
Last Modified: 25 Apr 2013 20:19
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28194

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