Linkage of the Indiana kindred of Gerstmann-Sträussler-Scheinker disease to the prion protein gene
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 (theta = 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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Some forms of prion disease can overlap with AD.
“Finally, not only can the neuropathologic changes of prion disease be co-morbid with AD, but some forms of prion disease can overlap with AD and need to be distinguished with special stains [23].”
From National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach (2012) · cites this paper as [23]
Prion disease neuropathologic changes can be co-morbid with AD.
“Finally, not only can the neuropathologic changes of prion disease be co-morbid with AD, but some forms of prion disease can overlap with AD and need to be distinguished with special stains [23].”
From National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach (2012) · cites this paper as [23]
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References 18 · Cited by 203
- Authors
- Dlouhy, S. R., Hsiao, K., Farlow, M. R., Foroud, T., Conneally, P. M., Johnson, P., Prusiner, S. B., Hodes, M. E., & Ghetti, B.
- Affiliations
- Indiana University Indianapolis (US)
- University of California, San Francisco (US)
- Venue
- Nature Genetics
- Published
- 1992-04
- Volume
- 1
- Issue
- 1
- Pages
- 64-67
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2025437195
- Cited by
- 203
- References
- 18
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 4 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 4 · 2014: 2 · 2013: 3 · 2012: 8
- FWCI
- 6.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Amyloidosis: Diagnosis, Treatment, Outcomes
- Keywords
- Gerstmann-Sträussler-Scheinker disease, prion protein gene, codon 129 polymorphism, genetic linkage, neurofibrillary tangles, amyloid plaques, age of onset, hereditary prion disease
- MeSH terms
- Adult, Age Factors, Aged, Amino Acid Sequence, Base Sequence, DNA, Female, Genetic Markers, Humans, Indiana, Genetic Linkage, Male, Middle Aged, Molecular Sequence Data, Pedigree, Prions, Gerstmann-Straussler-Scheinker Disease, Point Mutation, PrPSc Proteins
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