Pathologic evidence that the T188R mutation in PRNP is associated with prion disease.
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.
Memory and Aging Center, University of California, San Francisco, San Francisco, California, USA. mtartaglia@memory.ucsf.edu
Maria Carmela
MC
Tartaglia
Julie N
JN
Thai
Tricia
T
See
Amy
A
Kuo
Robert
R
Harbaugh
Benjamin
B
Raudabaugh
Ignazio
I
Cali
Mamta
M
Sattavat
Henry
H
Sanchez
Stephen J
SJ
DeArmond
Michael D
MD
Geschwind
D001120:Arginine / Q000235:genetics*; D007562:Creutzfeldt-Jakob Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology; D003704:Dementia / Q000150:complications / Q000235:genetics / Q000473:pathology; D017809:Fatal Outcome; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D017096:Prion Diseases / Q000150:complications / Q000235:genetics / Q000473:pathology; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*; D013912:Threonine / Q000235:genetics*
C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D013912:Threonine; D001120:Arginine