{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T09:23:06Z","timestamp":1776936186371,"version":"3.51.4"},"reference-count":42,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T00:00:00Z","timestamp":1631059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","award":["1NU38CK000480"],"award-info":[{"award-number":["1NU38CK000480"]}],"id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG068359"],"award-info":[{"award-number":["AG068359"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000320","name":"Alzheimer's Society","doi-asserted-by":"publisher","award":["AS-CTF-16b-007"],"award-info":[{"award-number":["AS-CTF-16b-007"]}],"id":[{"id":"10.13039\/501100000320","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Genetic prion disease accounts for 10\u201315% of prion disease. While insertion of four or more octapeptide repeats are clearly pathogenic, smaller repeat insertions have an unclear pathogenicity. The goal of this case series was to provide an insight into the characteristics of the 2-octapeptide repeat genetic variant and to provide insight into the risk for Creutzfeldt\u2013Jakob disease in asymptomatic carriers. 2-octapeptide repeat insertion prion disease cases were collected from the National Prion Disease Pathology Surveillance Center (US), the National Prion Clinic (UK), and the National Creutzfeldt\u2013Jakob Disease Registry (Australia). Three largescale population genetic databases were queried for the 2-octapeptide repeat insertion allele. Eight cases of 2-octapeptide repeat insertion were identified. The cases were indistinguishable from the sporadic Creutzfeldt\u2013Jakob cases of the same molecular subtype. Western blot characterization of the prion protein in the absence of enzymatic digestion with proteinase K revealed that 2-octapeptide repeat insertion and sporadic Creutzfeldt\u2013Jakob disease have distinct prion protein profiles. Interrogation of large-scale population datasets suggested the variant is of very low penetrance. The 2-octapeptide repeat insertion is at most a low-risk genetic variant. Predictive genetic testing for asymptomatic blood relatives is not likely to be justified given the low risk.<\/jats:p>","DOI":"10.3390\/v13091794","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T21:28:45Z","timestamp":1631136525000},"page":"1794","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Characterization of Prion Disease Associated with a Two-Octapeptide Repeat Insertion"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1099-3440","authenticated-orcid":false,"given":"Nicholas","family":"Brennecke","sequence":"first","affiliation":[{"name":"Department of Neurology, Case Western Reserve University & University Hospitals Cleveland Medical, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignazio","family":"Cali","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tze","family":"Mok","sequence":"additional","affiliation":[{"name":"MRC Prion Unit at University College London, Institute of Prion Diseases, London W1W 7FF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Speedy","sequence":"additional","affiliation":[{"name":"MRC Prion Unit at University College London, Institute of Prion Diseases, London W1W 7FF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Genomics England Research Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laszlo","family":"Hosszu","sequence":"additional","affiliation":[{"name":"MRC Prion Unit at University College London, Institute of Prion Diseases, London W1W 7FF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8282-9151","authenticated-orcid":false,"given":"Christiane","family":"Stehmann","sequence":"additional","affiliation":[{"name":"Australian National Creutzfeldt-Jakob Disease Registry, The Florey Institute, The University of Melbourne, Melbourne, VIC 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Cracco","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, School of Medicine, Indiana University, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianfranco","family":"Puoti","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, 81100 Caserta, Italy"},{"name":"Prion Disease Diagnosis and Surveillance Center (PDDSC), University of Campania \u201cLuigi Vanvitelli\u201d, 81100 Caserta, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Prior","sequence":"additional","affiliation":[{"name":"Center for Human Genetics Laboratory, Case Western Reserve University & University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Case Western Reserve University & University Hospitals Cleveland Medical, Cleveland, OH 44106, USA"},{"name":"Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Collins","sequence":"additional","affiliation":[{"name":"Australian National Creutzfeldt-Jakob Disease Registry, The Florey Institute, The University of Melbourne, Melbourne, VIC 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4326-1468","authenticated-orcid":false,"given":"Simon","family":"Mead","sequence":"additional","affiliation":[{"name":"MRC Prion Unit at University College London, Institute of Prion Diseases, London W1W 7FF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2275-3292","authenticated-orcid":false,"given":"Brian","family":"Appleby","sequence":"additional","affiliation":[{"name":"Department of Neurology, Case Western Reserve University & University Hospitals Cleveland Medical, Cleveland, OH 44106, USA"},{"name":"Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH 44106, USA"},{"name":"Department of Psychiatry, Case Western Reserve University & University Hospitals, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/B978-0-444-64076-5.00029-6","article-title":"Prion Disease","volume":"148","author":"Takada","year":"2018","journal-title":"Handb. 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