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Updated: Jun 6, 2026
Detection of Abnormal Prion Protein by Immunohistochemistry
Published on: May 5, 2023
Pathologic evidence that the T188R mutation in PRNP is associated with prion disease
Maria Carmela Tartaglia1, Julie N Thai, Tricia See
1Memory and Aging Center, University of California, San Francisco, San Francisco, California, USA. mtartaglia@memory.ucsf.edu
Abstract:
Human prion diseases can be caused by mutations in the prion protein gene PRNP. Prion disease with mutations at codon 188 has been reported in 6 cases, but only 1 had the T188R mutation and it was not pathologically confirmed. We report the clinical, neuropsychologic, imaging, genetic, and neuropathologic features of a patient with familial Creutzfeldt-Jakob disease, associated with a very rare PRNP mutation at T188R. The patient presented with prominent behavioral changes in addition to the more typical cognitive and motorimpairments seen in sporadic Creutzfeldt-Jakob disease. The autopsy confirmed prion disease pathology. This case supports the pathogenicity of the T188 PRNP mutation, demonstrates the variability of clinical phenotypes associated with certain mutations, and emphasizes the importance of testing for genetic prion disease in cases of apparently sporadic atypical dementia.
Insights
A rare T188R mutation in the prion protein gene (PRNP) causes familial Creutzfeldt-Jakob disease. This case highlights the mutation
Area of Science:
- Neuroscience
- Genetics
- Pathology
Background:
- Human prion diseases are linked to mutations in the prion protein gene (PRNP).
- Mutations at codon 188 of PRNP have been reported in six cases, but only one involved the T188R mutation, which lacked pathological confirmation.
Observation:
- A patient presented with familial Creutzfeldt-Jakob disease (CJD) and a rare PRNP mutation at T188R.
- Clinical manifestations included prominent behavioral changes alongside typical cognitive and motor impairments.
- Neuropathological examination confirmed prion disease pathology.
Findings:
- This case provides pathological confirmation for the T188R PRNP mutation.
- The study demonstrates significant clinical phenotype variability associated with specific PRNP mutations.
- The findings support the pathogenicity of the T188R PRNP mutation.
Implications:
- Genetic testing for prion disease is crucial in atypical dementia cases that appear sporadic.
- Understanding PRNP mutation pathogenicity aids in diagnosing and managing prion diseases.
- This research expands knowledge of genotype-phenotype correlations in human prion diseases.
