Journal ArticleDOI
Novel PRNP sequence variant associated with familial encephalopathy.
Larisa Cervenakova,Cathrin Buetefisch,Hee-Suk Lee,Inna Taller,Gary Stone,Clarence J. Gibbs,Paul Brown,Mark Hallett,Lev G. Goldfarb +8 more
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TLDR
A novel H187R mutation has been identified in affected, but not in unaffected, family members or unrelated controls suggesting a pathogenic role for this mutation.Abstract:
Human transmissible spongiform encephalopathies (TSEs) are a group of chronic progressive neurodegenerative disorders that may be hereditary, infectious, or sporadic. Hereditary TSEs are associated with mutations in the PRNP gene on chromosome 20p12-pter. We report on a family in which seven patients developed limb and truncal ataxia, dysarthria, myoclonic jerks, and cognitive decline. The age of onset in the 30s, 40s, or 50s, prolonged disease duration, cerebellar atrophy on imaging, and the presence of synchronic periodic discharges on electroencephalogram suggested a familial encephalopathy resembling Gerstmann-Straussler-Scheinker disease. A novel H187R mutation has been identified in affected, but not in unaffected, family members or unrelated controls suggesting a pathogenic role for this mutation. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:653-656, 1999. Published 1999 Wiley-Liss, Inc.read more
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Checking the pH-induced conformational transition of prion protein by molecular dynamics simulations: effect of protonation of histidine residues.
TL;DR: Simulations reveal a significant loss of alpha-helix content under mildly acidic conditions, due to destructuration of the C-terminal part of HB (thus suggesting a possible involvement of HB into the conformational transition leading to the pathogenic isoform) and a transient lengthening of the native beta-sheet.
Journal ArticleDOI
Genetic prion disease: Experience of a rapidly progressive dementia center in the United States and a review of the literature.
Leonel T. Takada,Mee-Ohk Kim,Ross W. Cleveland,Katherine Wong,Sven Forner,Ignacio Illán Gala,Jamie Fong,Michael D. Geschwind +7 more
TL;DR: The UCSF gPrD cohort is presented, including 129 symptomatic patients referred to and/or seen at UCSF between 2001 and 2016, and clinical features of the gPrDs from 22 mutations identified in this cohort are compared with data from the literature, as well as perform a literature review on most other mutations not represented in the cohort.
Journal ArticleDOI
Influence of pH on the human prion protein: insights into the early steps of misfolding.
TL;DR: Detailed molecular-dynamics simulations of the recombinant PrP protein in water at three different pH regimes provide a molecular basis for the initial steps in the misfolding process and are consistent with experimental data.
Journal ArticleDOI
Copper(II) complexes of peptide fragments of the prion protein. Conformation changes induced by copper(II) and the binding motif in C-terminal protein region
David R. Brown,Valeria Guantieri,Giulia Grasso,Giuseppe Impellizzeri,Giuseppe Pappalardo,Enrico Rizzarelli +5 more
TL;DR: The similarity of the EPR parameters suggests that the anchoring imidazole residue drives the copper(II) coordination environment towards a common binding motif in different regions of the prion protein.
Journal ArticleDOI
Genetic PrP Prion Diseases.
TL;DR: This review classification of genetic prion diseases as rapid, slow, or mixed types based on their typical rate of progression and duration, and the broad spectrum of phenotypes manifested by these diseases are reviewed.
References
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Journal ArticleDOI
Linkage of a prion protein missense variant to Gerstmann–Sträussler syndrome
Karen Hsiao,Harry F. Baker,Timothy J. Crow,Mark Poulter,Frank Owen,Joseph D. Terwilliger,David Westaway,Jurg Ott,Jurg Ott,Stanley B. Prusiner +9 more
TL;DR: It is shown here that PrP codon 102 is linked to the putative gene for the syndrome in two pedigrees, providing the best evidence to date that this familial condition is inherited despite also being infectious, and that substitution of leucine for proline at PrPcodon 102 may lead to the development of Gerstmann–Sträussler syndrome.
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Experimental Transmission of a Kuru-like Syndrome to Chimpanzees
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Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease
Paul D. Brown,C. J. Gibbs,Pamela Rodgers-Johnson,D. M. Asher,Sulima Mp,A. Bacote,L. G. Goldfarb,D. C. Gajdusek +7 more
TL;DR: Incubation periods as well as the durations and character of illness showed great variability, even in animals receiving the same inoculum, mirroring the spectrum of clinical profiles seen in human disease.
Journal ArticleDOI
Creutzfeldt-Jakob Disease (Spongiform Encephalopathy): Transmission to the Chimpanzee
C. J. Gibbs,D. C. Gajdusek,David M. Asher,Michael P. Alpers,Elizabeth Beck,Peter M. Daniel,W. B. Matthews +6 more
TL;DR: Biopsy material taken from the brain of a patient with CreutzfeldtJakob disease with status spongiosus induced a similar fatal encephalopathy in a chimpanzee 13 months after inoculation.
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Creutzfeldt‐Jakob disease: Patterns of worldwide occurrence and the significance of familial and sporadic clustering
TL;DR: The worldwide epidemiology of Creutzfeldt‐Jakob disease (CJD) is presented from an analysis of 1,435 patients, and fifteen percent of the cases were of the familial type, suggesting a genetic susceptibility to infection.