title: Genomic Characteristics of Genetic Creutzfeldt-Jakob Disease Patients with V180I Mutation and Associations with Other Neurodegenerative Disorders.
abstract: Inherited prion diseases (IPDs), including genetic Creutzfeldt-Jakob disease (gCJD), account for 10-15% of cases of prion diseases and are associated with several pathogenic mutations, including P102L, V180I, and E200K, in the prion protein gene (PRNP). The valine to isoleucine substitution at codon 180 (V180I) of PRNP is the most common pathogenic mutation causing gCJD in East Asian patients. In this study, we conducted follow-up analyses to identify candidate factors and their associations with disease onset. Whole-genome sequencing (WGS) data of five gCJD patients with V180I mutation and 145 healthy individuals were used to identify genomic differences. A total of 18,648,850 candidate variants were observed in only the patient group, 29 of them were validated as variants. Four of these validated variants were nonsense mutations, six were observed in genes directly or indirectly related to neurodegenerative disorders (NDs), such as LPA, LRRK2, and FGF20. More than half of validated variants were categorized in Gene Ontology (GO) terms of binding and/or catalytic activity. Moreover, we found differential genome variants in gCJD patients with V180I mutation, including one uniquely surviving 10 years after diagnosis of the disease. Elucidation of the relationships between gCJD and Alzheimer's disease or Parkinson's disease at the genomic level will facilitate further advances in our understanding of the specific mechanisms mediating the pathogenesis of NDs and gold standard therapies for NDs.
authors.affiliation: Division of Zoonoses, Center for Immunology & Pathology, National Institute of Health, Korea Centers for Disease Control & Prevention, Cheongju-si, Chungcheongbuk-do, South Korea.|Department of Agricultural Biotechnology, Animal Biotechnology Major, Seoul National University, Seoul, South Korea.
authors.forename: Sol Moe
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Division of Bio-Medical Informatics, Center for Genome Science, National Institute of Health, Korea Centers for Disease Control & Prevention, Cheongju-si, Chungcheongbuk-do, South Korea.|Division of Molecular and Life science, Hanyang University, Seoul, South Korea.
authors.forename: Myungguen
authors.initials: M
authors.lastname: Chung
authors.affiliation: Division of Zoonoses, Center for Immunology & Pathology, National Institute of Health, Korea Centers for Disease Control & Prevention, Cheongju-si, Chungcheongbuk-do, South Korea.
authors.forename: Jae Wook
authors.initials: JW
authors.lastname: Hyeon
authors.affiliation: Division of Bio-Medical Informatics, Center for Genome Science, National Institute of Health, Korea Centers for Disease Control & Prevention, Cheongju-si, Chungcheongbuk-do, South Korea.
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Jeong
authors.affiliation: Division of Zoonoses, Center for Immunology & Pathology, National Institute of Health, Korea Centers for Disease Control & Prevention, Cheongju-si, Chungcheongbuk-do, South Korea.
authors.forename: Young Ran
authors.initials: YR
authors.lastname: Ju
authors.affiliation: Department of Agricultural Biotechnology, Animal Biotechnology Major, Seoul National University, Seoul, South Korea.
authors.forename: Heebal
authors.initials: H
authors.lastname: Kim
authors.affiliation: Division of Zoonoses, Center for Immunology & Pathology, National Institute of Health, Korea Centers for Disease Control & Prevention, Cheongju-si, Chungcheongbuk-do, South Korea.
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, Gyeonggi-do, South Korea.
authors.forename: SangYun
authors.initials: S
authors.lastname: Kim
authors.affiliation: Gachon BioNano Research Institute, Gachon University, Gyeonggi-do, South Korea.
authors.forename: Seong Soo A
authors.initials: SS
authors.lastname: An
authors.affiliation: Division of Bio-Medical Informatics, Center for Genome Science, National Institute of Health, Korea Centers for Disease Control & Prevention, Cheongju-si, Chungcheongbuk-do, South Korea.
authors.forename: Sung Beom
authors.initials: SB
authors.lastname: Cho
authors.affiliation: Division of Zoonoses, Center for Immunology & Pathology, National Institute of Health, Korea Centers for Disease Control & Prevention, Cheongju-si, Chungcheongbuk-do, South Korea.
authors.forename: Yeong Seon
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Division of Zoonoses, Center for Immunology & Pathology, National Institute of Health, Korea Centers for Disease Control & Prevention, Cheongju-si, Chungcheongbuk-do, South Korea.
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution; D003062:Codon; D019295:Computational Biology; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D004843:Epistasis, Genetic; D005260:Female; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D000072002:Prion Proteins / Q000235:genetics*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D003062:Codon; D000072002:Prion Proteins; D016875:tau Proteins