Gerstmann-Sträussler-Scheinker disease and the Indiana kindred

Bernardino Ghetti, Stephen Dlouhy, Giorgio Giaccone, Orso Bugiani, Bias Frangione, Martin Farlow, Fabrizio Tagliavini

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Gerstmann-Sträussler-Scheinker disease is an autosomal dominant disorder with a wide spectrum of clinical presentations including ataxia, spastic paraparesis, extrapyramidal signs, and dementia. The patients present with symptoms in the third to sixth decade of life and the mean duration of illness is five years. Mutations at codons 102, 105, 117, 145, 198 and 217 of the open reading frame of the prion protein gene have been associated with GSS disease. As a result of the mutations, a substitution at the corresponding residues of the prion protein occurs, or as in the case of the STOP mutation at codon 145, a truncated protein is produced. Neuropathologically, the common denominator is a cerebral prion protein amyloidosis; however, there is significant variability in the pattern of amyloid deposition in regions of the central nervous system among reported families. Amyloidosis coexists with severe spongiform degeneration in patients with the mutation at codon 102, and with neurofibrillary degeneration in the patients with mutation at codons 145, 198 and 217. The development of a transmissible spongiform encephalopathy in animals inoculated with brain tissue from affected subjects with mutation at codon 102 suggests that in some formsofgenetically-determined Gerstmann-Sträussler-Scheinker disease, and particularly those characterized by severe spongiosis, amyloidogenesis and production of an infectious "agent" occur concomitantly via mechanisms that are only partially understood.

Original languageEnglish
Pages (from-to)61-75
Number of pages15
JournalBrain Pathology
Volume5
Issue number1
StatePublished - 1995

Fingerprint

Codon
Mutation
Amyloidosis
Spastic Paraparesis
Prion Diseases
Ataxia
Amyloid
Open Reading Frames
Dementia
Central Nervous System
Brain
Genes
Prion Proteins
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Ghetti, B., Dlouhy, S., Giaccone, G., Bugiani, O., Frangione, B., Farlow, M., & Tagliavini, F. (1995). Gerstmann-Sträussler-Scheinker disease and the Indiana kindred. Brain Pathology, 5(1), 61-75.

Gerstmann-Sträussler-Scheinker disease and the Indiana kindred. / Ghetti, Bernardino; Dlouhy, Stephen; Giaccone, Giorgio; Bugiani, Orso; Frangione, Bias; Farlow, Martin; Tagliavini, Fabrizio.

In: Brain Pathology, Vol. 5, No. 1, 1995, p. 61-75.

Research output: Contribution to journalArticle

Ghetti, B, Dlouhy, S, Giaccone, G, Bugiani, O, Frangione, B, Farlow, M & Tagliavini, F 1995, 'Gerstmann-Sträussler-Scheinker disease and the Indiana kindred', Brain Pathology, vol. 5, no. 1, pp. 61-75.
Ghetti, Bernardino ; Dlouhy, Stephen ; Giaccone, Giorgio ; Bugiani, Orso ; Frangione, Bias ; Farlow, Martin ; Tagliavini, Fabrizio. / Gerstmann-Sträussler-Scheinker disease and the Indiana kindred. In: Brain Pathology. 1995 ; Vol. 5, No. 1. pp. 61-75.
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