Fatal familial insomnia and familial Creutzfeldt-Jakob disease: Different prion proteins determined by a DNA polymorphism

Lucia Monari, Shu G. Chen, Paul Brown, Piero Parchi, Robert B. Petersen, Jacqueline Mikol, Franscoise Gray, Pietro Cortelli, Pasquale Montagna, Bernardino Ghetti, Lev G. Goldfarb, D. Carleton Gajdusek, Elio Lugaresi, Pierluigi Gambetti, Lucila Autilio-Gambetti

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2839-2842
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number7
DOIs
StatePublished - Mar 29 1994

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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. (1994). Fatal familial insomnia and familial Creutzfeldt-Jakob disease: Different prion proteins determined by a DNA polymorphism. Proceedings of the National Academy of Sciences of the United States of America, 91(7), 2839-2842. https://doi.org/10.1073/pnas.91.7.2839