Pathologic Evidence That the T188R Mutation in PRNP Is Associated With Prion Disease.
Tartaglia, Maria Carmela MD; Thai, Julie N. MSc; See, Tricia ScM; Kuo, Amy BSc; Harbaugh, Robert MD; Raudabaugh, Benjamin BSc; Cali, Ignazio MS; Sattavat, Mamta MS; Sanchez, Henry MD, PhD; DeArmond, Stephen J. MD, PhD; Geschwind, Michael D. MD, PhD
Journal of Neuropathology & Experimental Neurology.
69(12):1220-1227, December 2010.
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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 itwasnot 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 variabilityof clinical phenotypes associated with certain mutations, and emphasizes the importance of testing for genetic prion disease in casesof apparently sporadic atypical dementia.
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