A patient with Creutzfeldt-Jakob disease with an insertion of 7 octa-repeats in the PRNP gene: molecular characteristics and clinical features.
BACKGROUND
We evaluated the features of neuropathology, abnormal prion protein (PrP) molecules, and clinical data of a Chinese woman diagnosed with familiar Creutzfeldt-Jakob disease (CJD), having 7 octa-repeats inserted with codon 129 methionine homozygote in the PRNP gene.


METHODS
Neuropathologic characteristics of the brain were analyzed by hemotoxylin-eosin stain and electronic microscopy. The presence of abnormal PrP in brains was detected by proteinase K and PrP molecules were evaluated by deglycosylation assay.


RESULTS
Spongiform degeneration, with diffuse neuronal loss and mild astrocytic gliosis, as well as with profound degeneration of neurons and astrocytes was observed. Proteinase K-resistant PrP was deposited widely in various regions of the brain. Calculation of the glycosylation ratios of proteinase K-resistant PrP molecules identified that the monoglycosyl isomer was predominant. PrP deglycosylation tests allowed for the identification of a predominant 19-kDa PrP signal that represents a partially proteolytic C-terminal segment, a 27-kDa band that represents the full-length wild-type PrP molecule, and a 30-kDa band that probably corresponds to the full-length mutant PrP molecule.


CONCLUSIONS
: Sporadic CJD-like neuropathologic changes and deposits of proteinase K-resistant PrP have been identified in this familiar CJD case with a 168 base pair nucleotide insertion. The clinical features differ from previously reported cases that had 7 octa-repeat insertion, but bear similarities to sporadic CJD.
Guo
Yan-Jun
YJ
Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.
Wang
Xiao-Fan
XF
Han
Jun
J
Zhang
Bao-Yun
BY
Zhao
Wei-Qin
WQ
Shi
Qi
Q
Wan
Yan-Zhen
YZ
Gao
Chen
C
Li
Ji-Mei
JM
Wang
De-Xin
DX
Dong
Xiao-Ping
XP
D002540:Cerebral Cortex / Q000737:chemistry / Q000473:pathology; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid
D011328:Prions