OBJECTIVETo study the conversion of mutant D178N prion protein in RT-QuIC assay.

METHODSThe D178N mutant prion PRNP was generated by the method of single site mutation. The mutant PRNP gene was inserted into plasmids of pET24. The full and N-truncated recombinant human prion proteins were expressed and purified. The fibril formations of these proteins were real-time monitored by the method of RT-QuIC. The ability to resist proteinase K (PK) of these fibrils was analyzed.

RESULTSWe succeed to construct human PrP-D178N plamids. The N-truncated human prion protein with D178N (PrP90-231-D178N) can convert spontaneously in RT-QuIC, while full length of human prion D178N protein (PrP23-231-D178N) fails to convert spontaneously. The spontaneously generated fibril has been domenstrated it is partily PK-resistant.

CONCLUSIONThe N-terminal of prion protein (23-90) plays an important role for the D178N mutant protein spontaneously conversion, which provide the clues for study the pathogenesis of genetic CJD.

Creutzfeldt-Jakob Syndrome ; etiology ; Humans ; Mutant Proteins ; genetics ; Nucleic Acid Amplification Techniques ; methods ; Prions ; genetics

OBJECTIVETo investigate epidemiological, clinical and genetic features of the first Chinese case of Creutzfeldt-Jakob disease (CJD ) with mutation of E200K in PRNP.

METHODSThe general epidemiological and clinical data were collected; CSF 14-3-3 protein was analyzed by Western blot; The PRNP was amplified by PCR and analyzed.

RESULTSA missense mutation in codon 200 (E200K) of the PRNP was identified in this patient; CSF 14-3-3 protein was positive; sleep disturbance was the initial sign and the other symptoms gradually appeared, including memory loss, dizziness and ataxia.

CONCLUSIONThe CJD patient who was first reported in China has a missense mutation in codon 200 (E200K) of the PRNP, and the codon 129 is a methionine homozygous genotype.

Asian Continental Ancestry Group ; China ; Creutzfeldt-Jakob Syndrome ; genetics ; Humans ; Male ; Middle Aged ; Mutation, Missense ; Prion Proteins ; Prions ; genetics

Human genetic prion diseases (gPrDs) are directly associated with mutations and insertions in the PRNP (Prion Protein) gene. We collected and analyzed the data of 218 Chinese gPrD patients identified between Jan 2006 and June 2020. Nineteen different subtypes were identified and gPrDs accounted for 10.9% of all diagnosed PrDs within the same period. Some subtypes of gPrDs showed a degree of geographic association. The age at onset of Chinese gPrDs peaked in the 50-59 year group. Gerstmann-Sträussler-Scheinker syndrome (GSS) and fatal familial insomnia (FFI) cases usually displayed clinical symptoms earlier than genetic Creutzfeldt-Jakob disease (gCJD) patients with point mutations. A family history was more frequently recalled in P105L GSS and D178N FFI patients than T188K and E200K patients. None of the E196A gCJD patients reported a family history. The gCJD cases with point mutations always developed clinical manifestations typical of sporadic CJD (sCJD). EEG examination was not sensitive for gPrDs. sCJD-associated abnormalities on MRI were found in high proportions of GSS and gCJD patients. CSF 14-3-3 positivity was frequently detected in gCJD patients. Increased CSF tau was found in more than half of FFI and T188K gCJD cases, and an even higher proportion of E196A and E200K gCJD patients. 63.6% of P105L GSS cases showed a positive reaction in cerebrospinal fluid RT-QuIC. GSS and FFI cases had longer durations than most subtypes of gCJD. This is one of the largest studies of gPrDs in East Asians, and the illness profile of Chinese gPrDs is clearly distinct. Extremely high proportions of T188K and E196A occur among Chinese gPrDs; these mutations are rarely reported in Caucasians and Japanese.
14-3-3 Proteins/cerebrospinal fluid* ; China ; Creutzfeldt-Jakob Syndrome/genetics* ; Humans ; Mutation/genetics* ; Prion Diseases/genetics* ; Prion Proteins/genetics* ; Prions/genetics* ; tau Proteins/cerebrospinal fluid*

Aged ; Asian Continental Ancestry Group ; Creutzfeldt-Jakob Syndrome ; cerebrospinal fluid ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Insomnia, Fatal Familial ; cerebrospinal fluid ; genetics ; Male ; Middle Aged ; Mutation ; genetics

Creutzfeldt-Jakob disease (CJD) is an uncommon neurodegenerative disorder with an incidence of 1 per 1000,000 per year typically characterized by rapidly progressive dementia, ataxia, myoclonus and behavioral changes. Genetic prion diseases, which develop due to a mutations in the prion protein gene (PRNP), account for an estimated 10 to 15% of all CJD cases. We report a 75-yr-old woman with familial CJD carrying a V180I mutation which features late onset, slow progression, no periodic sharp wave complexes on electroencephalography, and extensive cortical ribboning with spared the cerebellum and the medial occipital lobes posterior to the parieto-occipital sulcus on MRI. To our knowledge, this is the first documented case of a point mutation at codon 180 in South Korea.
Aged ; Base Sequence ; Codon ; Creutzfeldt-Jakob Syndrome/*genetics/physiopathology ; DNA Mutational Analysis ; Female ; Humans ; Neuropsychological Tests ; *Point Mutation ; Prions/*genetics ; Republic of Korea

OBJECTIVETo describe the incidence condition and characteristic of Creutzfeldt-Jakob disease (CJD) in China.

METHODSThe clinical and epidemical information of patients from China CJD surveillance network was analyzed. Blood and cerebrospinal fluid (CSF) specimens from these patients were differently collected to be used to detect the 14-3-3 protein in the CSF and to analyze the PRNP gene.

RESULTSTen possible and 8 probable clinically diagnosed CJD patients were found. These patients had sporadic CJD. There were no geographic clustering and occupational risk with these patients. The mean age at onset of disease was approximately 60 years. The male to female ratio was approximately 1:1; rapidly progressive dementia was the main early symptom, which was present in 44% of patients.

CONCLUSIONThe geographic distribution, occupation, the ratio of male to female and the mean age of onset were consistent with the characteristics of sporadic CJD.

14-3-3 Proteins ; cerebrospinal fluid ; Adult ; Aged ; Blotting, Western ; China ; epidemiology ; Creutzfeldt-Jakob Syndrome ; cerebrospinal fluid ; epidemiology ; genetics ; Female ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Population Surveillance ; Prion Proteins ; Prions ; genetics