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Overall, sCJDVV1\u20132 subjects showed mixed clinical and histopathological features, which often correlated with the relative amounts of the corresponding PrP<jats:sup>D<\/jats:sup> type. However, type-specific phenotypic characteristics were only detected when the amount of the corresponding PrP<jats:sup>D<\/jats:sup> type exceeded 20\u201325%. Overall, original features of types 1 (T1) and 2 (T2) in sCJDVV1 and -VV2, including rostrocaudal relative distribution and conformational indicators, were maintained in sCJDVV1\u20132 except for one of the two components of T1 identified by electrophoretic mobility as T1<jats:sup>21<\/jats:sup>. The T1<jats:sup>21<\/jats:sup> conformational characteristics shifted in the presence of T2, inferring a conformational effect of PrP<jats:sup>D<\/jats:sup> T2 on T1<jats:sup>21<\/jats:sup>. The prevalence of sCJDVV1\u20132 was 23% or 57% of all sCJDVV cases, depending on whether standard or highly sensitive type-detecting procedures were adopted. This study, together with previous data from sCJDMM1\u20132 (methionine homozygosity at PrP gene codon 129) establishes the type-mixed sCJD variants as an important component of sCJD, which cannot be identified with current non-tissue based diagnostic tests of prion disease.<\/jats:p>","DOI":"10.1038\/s41598-020-58446-0","type":"journal-article","created":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T11:02:57Z","timestamp":1580382177000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Co-existence of PrPD types 1 and 2 in sporadic Creutzfeldt-Jakob disease of the VV subgroup: phenotypic and prion protein characteristics"],"prefix":"10.1038","volume":"10","author":[{"given":"Ignazio","family":"Cali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco","family":"Puoti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Smucny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul Michael","family":"Curtiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Cracco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuyuki","family":"Kitamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossana","family":"Occhipinti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark Lloyd","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian Stephen","family":"Appleby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Gambetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,30]]},"reference":[{"key":"58446_CR1","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1002\/1531-8249(199908)46:2<224::AID-ANA12>3.0.CO;2-W","volume":"46","author":"P Parchi","year":"1999","unstructured":"Parchi, P. et al. 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