Journal article
An inherited prion disease with a PrP P105L mutation: Clinicopathologic and PrP heterogeneity
Neurology, Vol.53(1), pp.181-188
1999
DOI: 10.1212/WNL.53.1.181
PMID: 10408557
Abstract
Objective: To clarify a clinical and neuropathologic phenotype of an inherited prion disease associated with a missense mutation at codon 105 in the prion protein (PrP) gene that was originally described as a variant of Gerstmann–Sträussler–Scheinker disease demonstrating spastic paraparesis.
Methods: Two siblings from a Japanese family are described. PrP gene analyses, neuropathologic studies with immunohistochemistry, and Western blot analysis of the PrP were performed.
Results: Both patients showed a missense (proline→leucine) mutation at codon 105 and a methionine/valine polymorphism at codon 129 of the PrP gene. Clinically, Patient 1 presented with progressive spastic paraparesis, ataxia, and dementia. Patient 2, the sister of Patient 1, showed prominent action myoclonus and dementia. Neuropathologically, multiple PrP-positive amyloid plaques and diffuse PrP deposition in the deep cortical layers were found in the cerebral cortex with primarily frontal dominant atrophy in both patients. Tau-positive pathologic structures including neurofibrillary tangles, neuropil threads, and dystrophic neurites around the plaques were abundant in the brain of Patient 2. In contrast, the tau pathology was scarce in Patient 1. Western blot analysis of the brain showed different patterns of detergent-insoluble PrP fragments between the patients.
Conclusions: Despite the identical codon 105 mutation and codon 129 polymorphism of the PrP gene, remarkable clinical and neuropathologic differences, and PrP heterogeneity were present between the affected siblings. The phenotypic variability might be related to PrP heterogeneity.
Details
- Title: Subtitle
- An inherited prion disease with a PrP P105L mutation: Clinicopathologic and PrP heterogeneity
- Creators
- M YAMADA - Tokyo Medical and Dental UniversityY ITOH - Department of Internal Medicine, Yokufukai Geriatric Hospital, Tokyo, JapanT KITAMOTO - Department of Neurological Science, Tohoku University School of Medicine, JapanE OTOMO - Department of Internal Medicine, Yokufukai Geriatric Hospital, Tokyo, JapanM MATSUSHITA - Department of Neuropathology, Tokyo Institute of Psychiatry, JapanH MIZUSAWA - Department of Neurology, Faculty of Medicine, Tokyo, JapanA INABA - Department of Neurology, Faculty of Medicine, Tokyo, JapanY WADA - Department of Neurology, Faculty of Medicine, Tokyo, JapanM TAKASHIMA - Department of Neurology, Faculty of Medicine, Tokyo, JapanS SATOH - Department of Neurology, Faculty of Medicine, Tokyo, JapanT KAMATA - Department of Neurology, Faculty of Medicine, Tokyo, JapanR OKEDA - Department of Neuropathology, Medical Research Institute, Tokyo, JapanT KAYANO - Department of Oral Pathology, Faculty of Dentistry, Tokyo Medical and Dental University, Tokyo, JapanN SUEMATSU - Department of Pathology, Yokufukai Geriatric Hospital, Tokyo, Japan
- Resource Type
- Journal article
- Publication Details
- Neurology, Vol.53(1), pp.181-188
- Publisher
- Lippincott Williams & Wilkins; Hagerstown, MD
- DOI
- 10.1212/WNL.53.1.181
- PMID
- 10408557
- ISSN
- 0028-3878
- eISSN
- 1526-632X
- Language
- English
- Date published
- 1999
- Academic Unit
- Iowa Neuroscience Institute; Anesthesia; Neuroscience and Pharmacology
- Record Identifier
- 9984071707502771
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