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

Nature Genetics volume 1, pages 64–67 (1992)Cite this article

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.

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Authors and Affiliations

  1. Departments of Medical and Molecular Genetics, Pathology and/or Neurology, Indiana University School of Medicine, Indianapolis, Indiana, 46202-5251, USA

    Stephen R. Dlouhy, Martin R. Farlow, Tatiana Foroud, P. Michael Conneally, Patricia Johnson, M. E. Hodes & Bernardino Ghetti

  2. Departments of Neurology and/or Biochemistry and Biophysics, University of California, San Francisco, California, 94143, USA

    Karen Hsiao & Stanley B. Prusiner

Authors
  1. Stephen R. Dlouhy
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  2. Karen Hsiao
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  3. Martin R. Farlow
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  4. Tatiana Foroud
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  5. P. Michael Conneally
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  6. Patricia Johnson
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  7. Stanley B. Prusiner
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  8. M. E. Hodes
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  9. Bernardino Ghetti
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Dlouhy, S., Hsiao, K., Farlow, M. et al. Linkage of the Indiana kindred of Gerstmann-Sträussler-Scheinker disease to the prion protein gene. Nat Genet 1, 64–67 (1992). https://doi.org/10.1038/ng0492-64

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  • DOI: https://doi.org/10.1038/ng0492-64

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