Linkage of the Indiana kindred of Gerstmann-Sträussler-Scheinker disease to the prion protein gene.
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.
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis 46202-5251.
S R
SR
Dlouhy
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K
Hsiao
M R
MR
Farlow
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Foroud
P M
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Conneally
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Johnson
S B
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Prusiner
M E
ME
Hodes
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Ghetti
D000328:Adult; D000367:Age Factors; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D016098:Gerstmann-Straussler-Scheinker Disease / Q000235:genetics*; D006801:Humans; D007196:Indiana; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D018620:PrPSc Proteins; D011328:Prions / Q000235:genetics*
D005819:Genetic Markers; D018620:PrPSc Proteins; D011328:Prions; D004247:DNA