Absence of association between the incidence of BK virus and sporadic Creutzfeldt-Jakob disease.

BACKGROUND: Many studies suggest that the virus-like particles are required for the infection of Creutzfeldt-Jakob disease (CJD). OBJECTIVE: To determine the relationship between BK polyomavirus (BKV) and sporadic CJD. MATERIALS AND METHODS: We investigated the prevalence of BKV in urine samples from 94 sporadic CJD patients and 54 other neurological disease (OND) patients using polymerase chain reaction. RESULTS: BKV DNA was detected in 16 (17%) and 9 (16.7%) urine samples from sporadic CJD and OND patients, respectively. There was no significant difference in the incidence of BKV infection between Korean sporadic CJD and OND patients (p = 0.9558). In order to investigate the genotypes of BKV, we analyzed 22 BKV isolates obtained from Korean patients by DNA sequencing and nucleotide sequence analysis. Three distinct subtypes, namely I, III, and IV, were found in 66.7, 22.2, and 11.1% of 9 BKV isolates from OND patients, whereas subtypes I and IV were detected in 76.9 and 23.1% of 13 BKV isolates from sporadic CJD patients. Interestingly, subtype III was not detected in sporadic CJD patients. Significant differences in the frequency of BKV genotypes were not observed between sporadic CJD and OND patients. CONCLUSIONS: These results indicate that BKV may not play an important role in the pathogenesis of prion diseases.

Familial Creutzfeldt-Jakob disease with a mutation at codon 180 presenting with an atypical phenotype.

The clinical features of familial Creutzfeldt-Jakob disease (fCJD) with a mutation at codon 180 (V180I) are less typical than those of patients with sporadic CJD. We describe a patient with pathologically confirmed CJD carrying the V180I mutation who had atypical cerebrospinal fluid and electroencephalography findings. Similar to other prion protein mutations, this report suggests that the V180I mutation is not the exclusive determinant of the phenotype.

Dura mater graft-associated Creutzfeldt-Jakob disease: the first case in Korea.

Since 1987, dura mater graft-associated iatrogenic Creutzfeldt-Jakob disease (dCJD) has been reported in many countries. We report the first case of dCJD in Korea. A 54-yr-old woman, who underwent resection of the meningioma in the left frontal region and received a dura mater graft 23 yr ago presented with dysesthesia followed by psychiatric symptoms and ataxia. Her neurological symptoms rapidly progressed to such an extent that she exhibited myoclonus, dementia, and pyramidal and extrapyramidal signs within 8 weeks. The 14-3-3 protein was detected in her cerebrospinal fluid; however, an electroencephalogram did not reveal characteristic positive sharp wave complexes. Diffusion-weighted magnetic resonance images, obtained serially over 64 days, revealed the rapid progression of areas of high signal intensity in the caudate nucleus and cingulate gyrus to widespread areas of high signal intensity in the cortex and basal ganglia. Pathological examination of brain biopsy specimens confirmed the presence of spongiform changes and deposition of prion protein in the neurons and neuropils.

Absence of association between two HECTD2 polymorphisms and sporadic Creutzfeldt-Jakob disease.

BACKGROUND: HECT (homologous to E6-AP carboxyl terminus) E3 ubiquitin ligases are fundamental components of the eukaryotic ubiquitin-proteasome system and are involved in the pathogenesis of several human diseases, including polyglutamine diseases. HECTD2, an E3 ubiquitin ligase, has been linked to the incubation time of prion disease in mice, and its polymorphisms have been associated with sporadic Creutzfeldt-Jakob disease (CJD) in the British population. OBJECTIVE: To investigate whether 2 HECTD2 polymorphisms, -247G→A (rs7081363) and +16066T→A (rs12249854), are associated with sporadic CJD in the Korean population. METHODS: We compared the genotype, allele and haplotype frequencies of the 2 HECTD2 polymorphisms in 205 sporadic CJD patients to those of 208 healthy Koreans. RESULTS AND CONCLUSION: Our study does not show significant differences in the genotype and allele frequencies of these 2 polymorphisms between sporadic CJD and normal controls. Significant differences in the haplotype frequencies of these 2 polymorphisms were not observed between sporadic CJD and normal controls either. Our results indicate that these 2 HECTD2 polymorphisms are not associated with genetic susceptibility to sporadic CJD in a Korean population. This is the first genetic association study of HECTD2 with sporadic CJD in an Asian population.

Familial Creutzfeldt-Jakob disease with V180I mutation.

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.

Involvement of peptidylarginine deiminase-mediated post-translational citrullination in pathogenesis of sporadic Creutzfeldt-Jakob disease.

Peptidylarginine deiminases (PADs)-mediated post-translational citrullination processes play key roles in protein functions and structural stability through the conversion of arginine to citrulline in the presence of excessive calcium concentrations. In brain, PAD2 is abundantly expressed and can be involved in citrullination in disease. Recently, we have reported pathological characterization of PAD2 and citrullinated proteins in scrapie-infected mice, but the implication of protein citrullination in the pathophysiology in human prion disease is not clear. In the present study, we explored the molecular and biological involvement of PAD2 and the pathogenesis of citrullinated proteins in frontal cortex of patients with sporadic Creutzfeldt-Jakob disease (sCJD). We found increased expression of PAD2 in reactive astrocytes that also contained increased levels of citrullinated proteins. In addition, PAD activity was significantly elevated in patients with sCJD compared to controls. From two-dimensional gel electrophoresis and MALDI-TOF mass analysis, we found various citrullinated candidates, including cytoskeletal and energy metabolism-associated proteins such as vimentin, glial fibrillary acidic protein, enolase, and phosphoglycerate kinase. Based on these findings, our investigations suggest that PAD2 activation and aberrant citrullinated proteins could play a role in pathogenesis and have value as a marker for the postmortem classification of neurodegenerative diseases.