{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T10:35:54Z","timestamp":1769855754057,"version":"3.49.0"},"reference-count":33,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology of China","award":["2019YFC0118600"],"award-info":[{"award-number":["2019YFC0118600"]}]},{"name":"Ministry of Science and Technology of China","award":["81971011"],"award-info":[{"award-number":["81971011"]}]},{"name":"Ministry of Science and Technology of China","award":["D171100008217005"],"award-info":[{"award-number":["D171100008217005"]}]},{"name":"Ministry of Science and Technology of China","award":["7202060"],"award-info":[{"award-number":["7202060"]}]},{"name":"Ministry of Science and Technology of China","award":["QNPY2021001"],"award-info":[{"award-number":["QNPY2021001"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2019YFC0118600"],"award-info":[{"award-number":["2019YFC0118600"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971011"],"award-info":[{"award-number":["81971011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["D171100008217005"],"award-info":[{"award-number":["D171100008217005"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["7202060"],"award-info":[{"award-number":["7202060"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["QNPY2021001"],"award-info":[{"award-number":["QNPY2021001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Beijing Municipal Science and Technology Committee","award":["2019YFC0118600"],"award-info":[{"award-number":["2019YFC0118600"]}]},{"name":"Beijing Municipal Science and Technology Committee","award":["81971011"],"award-info":[{"award-number":["81971011"]}]},{"name":"Beijing Municipal Science and Technology Committee","award":["D171100008217005"],"award-info":[{"award-number":["D171100008217005"]}]},{"name":"Beijing Municipal Science and Technology Committee","award":["7202060"],"award-info":[{"award-number":["7202060"]}]},{"name":"Beijing Municipal Science and Technology Committee","award":["QNPY2021001"],"award-info":[{"award-number":["QNPY2021001"]}]},{"name":"Xuanwu Hospital Science Program for Fostering Young Scholars","award":["2019YFC0118600"],"award-info":[{"award-number":["2019YFC0118600"]}]},{"name":"Xuanwu Hospital Science Program for Fostering Young Scholars","award":["81971011"],"award-info":[{"award-number":["81971011"]}]},{"name":"Xuanwu Hospital Science Program for Fostering Young Scholars","award":["D171100008217005"],"award-info":[{"award-number":["D171100008217005"]}]},{"name":"Xuanwu Hospital Science Program for Fostering Young Scholars","award":["7202060"],"award-info":[{"award-number":["7202060"]}]},{"name":"Xuanwu Hospital Science Program for Fostering Young Scholars","award":["QNPY2021001"],"award-info":[{"award-number":["QNPY2021001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The majority of seven-octapeptide repeat insertion (7-OPRI) carriers exhibit relatively early onset and a slowly progressive course. We have presented three cases of 7-OPRI, including two that are rapidly progressing, and compared the clinical and ancillary characteristics of the short-term and long-term disease course, as well as factors that influence disease course. The clinical and ancillary features of three new 7-OPRI patients in a Chinese pedigree were analyzed. Global data on 7-OPRI cases were then collected by reviewing the literature, and the cases were grouped according to clinical duration as per the WHO sCJD criteria, with a two-year cut-off. A Chinese pedigree has a glycine-to-glutamate substitution within the 7-OPRI insertion, which enhances the hydrophilicity of the prion protein. Two cases in this pedigree had a short disease course (consistent with the typical clinical and ancillary features of sCJD). In addition, the members of this pedigree had a later onset (p &lt; 0.001) and shorter disease course (p &lt; 0.001) compared to previously reported 7-OPRI cases with 129 cis-M and a similar age of onset and disease course to that of cases with 129 cis-V. The 7-OPRI cases with a shorter clinical course (n = 4) had a later onset (p = 0.021), higher rate of hyperintensity on MRI (p = 0.029) and higher frequency of 129 cis-V (p = 0.066) compared to those with a longer clinical course (n = 13). The clinical presentation of 7-OPRI is significantly heterogeneous. Codon 129 cis-V and amino acid substitution within repeat insertions are possible contributors to the short-term disease course of 7-OPRI.<\/jats:p>","DOI":"10.3390\/v14102245","type":"journal-article","created":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T01:44:13Z","timestamp":1665711853000},"page":"2245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Amino Acid Substitution within Seven-Octapeptide Repeat Insertions in the Prion Protein Gene Associated with Short-Term Course"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhongyun","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haitian","family":"Nan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a033134","DOI":"10.1101\/cshperspect.a033134","article-title":"Genetic PrP Prion Diseases","volume":"10","author":"Kim","year":"2018","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11980","DOI":"10.1074\/jbc.273.19.11980","article-title":"Abnormal properties of prion protein with insertional mutations in different cell types","volume":"273","author":"Priola","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1110\/ps.051822606","article-title":"Octapeptide repeat insertions increase the rate of protease-resistant prion protein formation","volume":"15","author":"Moore","year":"2006","journal-title":"Protein Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"11576","DOI":"10.1073\/pnas.0903807106","article-title":"Functional implications of multistage copper binding to the prion protein","volume":"106","author":"Hodak","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1093\/brain\/awl226","article-title":"Inherited prion disease with six octapeptide repeat insertional mutation--molecular analysis of phenotypic heterogeneity","volume":"129","author":"Mead","year":"2006","journal-title":"Brain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/ajmg.b.32505","article-title":"Genetic prion disease: Experience of a rapidly progressive dementia center in the United States and a review of the literature","volume":"174","author":"Takada","year":"2017","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s00401-010-0656-3","article-title":"A novel seven-octapeptide repeat insertion in the prion protein gene (PRNP) in a Dutch pedigree with Gerstmann-Str\u00e4ussler-Scheinker disease phenotype: Comparison with similar cases from the literature","volume":"121","author":"Jansen","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10926","DOI":"10.1073\/pnas.88.23.10926","article-title":"Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene","volume":"88","author":"Goldfarb","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","first-page":"1306","article-title":"Recent advances in the research of Creutzfeldt-Jakob disease (CJD) and Gerstmann-Str\u00fcssler syndrome (GSS)","volume":"31","author":"Tateishi","year":"1991","journal-title":"Rinsho Shinkeigaku"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1212\/WNL.42.2.422","article-title":"Atypical Creutzfeldt-Jakob disease in an American family with an insert mutation in the PRNP amyloid precursor gene","volume":"42","author":"Brown","year":"1992","journal-title":"Neurology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1007\/s004150050603","article-title":"Familial Creutzfeldt-Jakob disease in a patient carrying both a presenilin 1 missense substitution and a prion protein gene insertion","volume":"247","author":"Dermaut","year":"2000","journal-title":"J. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1212\/01.WNL.0000065887.14609.0E","article-title":"Novel prion protein insert mutation associated with prolonged neurodegenerative illness","volume":"60","author":"Lewis","year":"2003","journal-title":"Neurology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1136\/jnnp.2007.121137","article-title":"De novo seven extra repeat expanded mutation in the PRNP gene in an Italian patient with early onset dementia","volume":"78","author":"Cannella","year":"2007","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1136\/jnnp.2007.142976","article-title":"A novel insertional mutation in the prion protein gene: Clinical and bio-molecular findings","volume":"79","author":"Mauro","year":"2008","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1136\/jnnp.2006.09433","article-title":"Creutzfeldt-Jakob disease in a Chinese patient with a novel seven extra-repeat insertion in PRNP","volume":"78","author":"Wang","year":"2007","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1097\/MAJ.0b013e3181643e50","article-title":"A patient with Creutzfeldt-Jakob disease with an insertion of 7 octa-repeats in the PRNP gene: Molecular characteristics and clinical features","volume":"336","author":"Guo","year":"2008","journal-title":"Am. J. Med. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"150","DOI":"10.3389\/fncel.2020.00150","article-title":"Case Report: Histopathology and Prion Protein Molecular Properties in Inherited Prion Disease With a De Novo Seven-Octapeptide Repeat Insertion","volume":"14","author":"Cali","year":"2020","journal-title":"Front. Cell Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s00401-010-0760-4","article-title":"Genetic Creutzfeldt-Jakob disease and fatal familial insomnia: Insights into phenotypic variability and disease pathogenesis","volume":"121","author":"Capellari","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"699836","DOI":"10.3389\/fnagi.2021.699836","article-title":"The Frequency of Genetic Mutations Associated With Behavioral Variant Frontotemporal Dementia in Chinese Han Patients","volume":"13","author":"Liu","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Gao, C., Shi, Q., Tian, C., Chen, C., Han, J., Zhou, W., Zhang, B.-Y., Jiang, H.-Y., Zhang, J., and Dong, X.-P. (2011). The epidemiological, clinical, and laboratory features of sporadic Creutzfeldt-Jakob disease patients in China: Surveillance data from 2006 to 2010. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024231"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s12264-019-00354-z","article-title":"T188K-Familial Creutzfeldt-Jacob Disease, Predominant Among Chinese, has a Reactive Pattern in CSF RT-QuIC Different from D178N-Fatal Familial Insomnia and E200K-Familial CJD","volume":"35","author":"Xiao","year":"2019","journal-title":"Neurosci. Bull."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1001\/archneur.1996.00550020074017","article-title":"Accuracy and reliability of periodic sharp wave complexes in Creutzfeldt-Jakob disease","volume":"53","author":"Steinhoff","year":"1996","journal-title":"Arch. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3162","DOI":"10.1093\/brain\/awac187","article-title":"Brain atrophy in prodromal synucleinopathy is shaped by structural connectivity and gene expression","volume":"145","author":"Rahayel","year":"2022","journal-title":"Brain"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1136\/jnnp-2021-328720","article-title":"Methionine homozygosity for PRNP polymorphism and susceptibility to human prion diseases","volume":"93","author":"Kosami","year":"2022","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1001\/jamaneurol.2015.4885","article-title":"Clinical Trial Simulations Based on Genetic Stratification and the Natural History of a Functional Outcome Measure in Creutzfeldt-Jakob Disease","volume":"73","author":"Mead","year":"2016","journal-title":"JAMA Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1212\/WNL.54.8.1641","article-title":"Neuropathologic variants of sporadic Creutzfeldt-Jakob disease and codon 129 of PrP gene","volume":"54","author":"Hauw","year":"2000","journal-title":"Neurology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1111\/j.1750-3639.1998.tb00172.x","article-title":"Clinical features of fatal familial insomnia: Phenotypic variability in relation to a polymorphism at codon 129 of the prion protein gene","volume":"8","author":"Montagna","year":"1998","journal-title":"Brain Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1136\/jnnp-2021-327247","article-title":"Clinical profile of fatal familial insomnia: Phenotypic variation in 129 polymorphisms and geographical regions","volume":"93","author":"Zhang","year":"2022","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1093\/brain\/awm063","article-title":"Creutzfeldt-Jakob disease in Germany: A prospective 12-year surveillance","volume":"130","author":"Heinemann","year":"2007","journal-title":"Brain"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1212\/01.wnl.0000267642.41594.9d","article-title":"Inherited prion disease with 5-OPRI: Phenotype modification by repeat length and codon 129","volume":"69","author":"Mead","year":"2007","journal-title":"Neurology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1097\/WAD.0b013e31818323ef","article-title":"Correlating DWI MRI with pathologic and other features of Jakob-Creutzfeldt disease","volume":"23","author":"Geschwind","year":"2009","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1212\/WNL.0b013e3181a18846","article-title":"Pathologic correlates of diffusion MRI changes in Creutzfeldt-Jakob disease","volume":"72","author":"Manners","year":"2009","journal-title":"Neurology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s00702-018-1958-1","article-title":"Disease duration in E200K familial Creutzfeldt-Jakob disease is correlated with clinical, radiological, and laboratory variables","volume":"126","author":"Cohen","year":"2019","journal-title":"J. Neural Transm."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/10\/2245\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:53:17Z","timestamp":1760143997000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/10\/2245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,13]]},"references-count":33,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["v14102245"],"URL":"https:\/\/doi.org\/10.3390\/v14102245","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,13]]}}}