Journal
NEUROLOGY
Volume 71, Issue 18, Pages 1431-1438Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/01.wnl.0000330237.94742.fa
Keywords
-
Categories
Funding
- NIH [NIH R01 NS46037, NIH R01 NS051480]
- Brain Research Foundation, Chicago, IL
- John Miko Foundation
- Pioneer Fund
Ask authors/readers for more resources
Objective: To define the clinicopathologic, genetic, and pathogenic prion protein (PrPSc) characteristics associated with a novel mutation of the prion protein gene (PRNP). Methods: The coding segment of PRNP from the proband and family members was sequenced and the brain of the proband was histologically studied. The Western blot profile of the proteinase K (PK) resistant fraction of PrPSc, an approximation of its conformation, or PrPSc-type, was determined. Results: We detected a novel mutation at codon 105 of PRNP that results in a serine (S) substitution of proline (P) (P105S), in a young woman who developed progressive aphasia, behavioral changes, dementia, and parkinsonism, lasting 10 years to her death. Histopathologic findings included an intense focus of multicentric PrP-plaques within the hippocampus, punctate plaques scattered throughout the cerebellum, and intense spongiform degeneration focally within the putamen, suggesting a variant of Gerstmann-Straussler-Scheinker syndrome (GSS). However, PrPSc-typing revealed two PK-resistant PrPSc fragments (similar to 21 and 26 kDa), a pattern not previously detected in GSS. Conclusions: This mutation is the third sequence variation at codon 105 of PRNP. The unusual phenotype and PrPSc-type distinguishes this genetic prion disease from typical Gerstmann-Straussler-Scheinker syndrome and other codon 105 substitutions, suggesting that, in addition to the loss of proline at this position, the PrPSc conformation and phenotype is dependent on the specific amino acid substitution. Neurology (R) 2008;71:1431-1438
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available