Pathologic Evidence That the T188R Mutation in PRNP Is Associated With Prion Disease

作者：Tartaglia Maria Carmela^*; Thai Julie N; See Tricia; Kuo Amy; Harbaugh Robert; Raudabaugh Benjamin; Cali Ignazio; Sattavat Mamta; Sanchez Henry; DeArmond Stephen J; Geschwind Michael D

来源：Journal of Neuropathology and Experimental Neurology, 2010, 69(12): 1220-1227.

DOI：10.1097/NEN.0b013e3181ffc39c

• Codon 188
• Creutzfeldt-Jakob disease
• Dementia
• Genetic
• Prion

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 motor impairments 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.

• 出版日期2010-12