Linkage of the Indiana kindred of Gerstmann-Sträussler-Scheinker disease to the prion protein gene

Stephen Dlouhy, Karen Hsiao, Martin Farlow, Tatiana Foroud, P. Michael Conneally, Patricia Johnson, Stanley B. Prusiner, M. E. Hodes, Bernardino Ghetti

Research output: Contribution to journalArticle

175 Citations (Scopus)

Abstract

The Indiana kindred variant of Gerstmann-Sträussler-Scheinker disease has amyloid plaques that contain prion protein (PrP), but is atypical because neurofibrillary tangles like those of Alzheimer disease are present. To map the position of the disease causing gene, we used three markers for linkage analyses. A missense mutation at codon 198 of the PrP gene (PRNP) is found in all definitely affected individuals and yields a maximum lod score of 6.37 (θ= 0). The disease also is concordant with the two other PRNP-region markers. These results demonstrate tight linkage of the disease-causing gene to PRNP and support the hypothesis that the codon 198 mutation is the cause of IK-GSS. Our studies also suggest that methionine/valine heterozygotes at PRNP codon 129 have a later age of onset of the disease than codon 129 valine/valine homozygotes.

Original languageEnglish
Pages (from-to)64-67
Number of pages4
JournalNature Genetics
Volume1
Issue number1
StatePublished - Apr 1992

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Prion Diseases
Codon
Valine
Genes
Lod Score
Neurofibrillary Tangles
Amyloid Plaques
Homozygote
Missense Mutation
Heterozygote
Age of Onset
Methionine
Alzheimer Disease
Mutation
Prion Proteins

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Linkage of the Indiana kindred of Gerstmann-Sträussler-Scheinker disease to the prion protein gene. / Dlouhy, Stephen; Hsiao, Karen; Farlow, Martin; Foroud, Tatiana; Conneally, P. Michael; Johnson, Patricia; Prusiner, Stanley B.; Hodes, M. E.; Ghetti, Bernardino.

In: Nature Genetics, Vol. 1, No. 1, 04.1992, p. 64-67.

Research output: Contribution to journalArticle

Dlouhy, Stephen ; Hsiao, Karen ; Farlow, Martin ; Foroud, Tatiana ; Conneally, P. Michael ; Johnson, Patricia ; Prusiner, Stanley B. ; Hodes, M. E. ; Ghetti, Bernardino. / Linkage of the Indiana kindred of Gerstmann-Sträussler-Scheinker disease to the prion protein gene. In: Nature Genetics. 1992 ; Vol. 1, No. 1. pp. 64-67.
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