Genetic Studies in Human Prion Diseases

Human prion diseases are fatal neurodegenerative disorders that are characterized by spongiform changes, astrogliosis, and the accumulation of an abnormal prion protein (PrP(Sc)). Approximately 10%-15% of human prion diseases are familial variants that are caused by pathogenic mutations in the prion protein gene (PRNP). Point mutations or the insertions of one or more copies of a 24 bp repeat are associated with familial human prion diseases including familial Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome, and fatal familial insomnia. These mutations vary significantly in frequency between countries. Here, we compare the frequency of PRNP mutations between European countries and East Asians. Associations between single nucleotide polymorphisms (SNPs) of several candidate genes including PRNP and CJD have been reported. The SNP of PRNP at codon 129 has been shown to be associated with sporadic, iatrogenic, and variant CJD. The SNPs of several genes other than PRNP have been showed contradictory results. Case-control studies and genome-wide association studies have also been performed to identify candidate genes correlated with variant and/or sporadic CJD. This review provides a general overview of the genetic mutations and polymorphisms that have been analyzed in association with human prion diseases to date.

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.

Follicular stimulating hormone enhances Notch 1 expression in SK-OV-3 ovarian cancer cells / 부인종양

OBJECTIVE: Notch is known as a transmembranous receptor family with four homologous forms - Notch 1, Notch 2, Notch 3, and Notch 4 and related to cell fate regulation and angiogenesis. The purpose is to investigate the effect of follicular stimulating hormone (FSH) on the Notch 1 expression and proliferation in ovarian cancer cells. METHODS: Human ovarian cancer cell line, SK-OV-3 and FSH were used. XTT cell proliferation and cell migration assay were carried out with FSH 100 mIU/mL and Notch 1 siRNA. Western blots and reverse transcriptase-polymerase chain reactions (RT-PCR) were carried out to determine the expression level of the Notch 1 protein and mRNA with FSH treatment in 0, 1, 5, 10, 100, 200, 300 mIU/mL concentrations. Immunofluorescent (IF) stains were performed in SK-OV-3 cell cultures with FSH 100 mIU/mL. Student-t tests were used in statistical analyses. RESULTS: The SK-OV-3 have Notch 1 receptors in their natural status. FSH stimulated SK-OV-3 cells in XTT cell proliferation and cell migration assays and notch 1 siRNA inhibited. The expression level of Notch 1 protein and mRNA were increased in a dose dependent pattern according to FSH concentrations compared to untreated cells. IF stains also showed brighter Notch1 expressions in the FSH treated cells compared to the control cells. CONCLUSION: FSH enhances proliferation & migration and Notch 1 signaling in SK-OV-3 cells. The Notch signaling probably supports one of the cell proliferating mechanisms of FSH in ovarian cancer cells.

Development of Policy and Strategy for the Control of Creutzfeldt-Jakob Disease in Korea / 한국역학회지

PURPOSE: Through the understanding of the current status of transmissible spongiform encephalopathy(TSE), this study was conducted to contribute to the development of policy and strategy for the control of TSE in Korea in order to keep Korea as a bovine spongiform encephalopathy(BSE)- and variant Creutzfeldt-Jakob disease(vCJD)-free country. BSE and vCJD cases have not been found in Korea. During 2001-2004, the number of patients who have been diagnosed as a definite or probable CJD was 121, which are consisted of 62 male and 59 female(average age: 63 years old). The occurrence of the patients was 5-59 people per year until 2003 and has been gradually increasing due to the recent increase in the diagnostic rate rather than the increase of the incidence. In 2004, the annual occurrence of sporadic CJD(sCJD) in Korea was 1 people per million, which is similar to the average occurrence rate of the world. Two cases of chronic wasting disease(CWD) in deer were found in Chungcheongbuk-do, one in August 2001 and one in October 2001. After that, 4 more CWD-affected deer have been reported in Kyungsangnam-do area in November 2004. We have also examined the possibility that Korean CJD occurred as a result of dietary exposure to BSE. Fortunately, all of Korean CJD patients were not vCJD cases. However, if BSE occurs in Korea, there is a great potential for most of the Korean population to be easily infected with BSE due to their highly susceptible genotype to BSE infection as well as their traditional food habit. In 2003, the total number of people who left Korea was almost identical with the total number of people who entered Korea. However, we could not analyze the number of people who visited or stayed in the UK and Europe during 1980s~1990s, in which BSE was prevalent in Europe, because there was no statistical data available.

Clinical Presentation of Immunohistochemicially Proven Sporadic Creutzfeldt-Jakob Disease

BACKGROUND: Creutzfeldt-Jakob disease is a rapidly progressive, ultimately lethal dementing illness caused by an infectious protein named prion. We present clinical characterisitics, laboratory findings and natural courses of immuno-histochemicially proven sporadic CJD patients. METHODS: The subjects consisted of 5 patients who were confirmed by brain biopsy with immunohistochemistry. We analyzed prodromal symptoms, clinical characteristics, disease duration and laboratory findings retrospectively. RESULTS: The mean age of the patients was 60.2+/-5.8. The prodromal symptoms were variable including dizziness, ataxia, vertigo, imbalance, headache, visual hallucination, visual blurring and ble-pharospasm. The EEG findings showed periodic sharp and wave complexes in all of the patients. MRI findings of 3 patients were high signal intensity in bilateral basal ganglia on T2 weighted and FLAIR images, and DWI showed high signal intensity in temporo-occipital lobe in a patient of Heidenhain variant. CONCLUSIONS: The prodromal symptoms and laboratory findings are not so different from previous report. And we suggest that the only way to confirm the diagnosis of Creutzfeldt Jakob disease is to ascertain the PrP sc in brain tissue through immunohistochemistry. (J Korean Neurol Assoc 19(5):464~470, 2001)