{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:46:44Z","timestamp":1790398004853,"version":"4.1.0"},"reference-count":30,"publisher":"BMJ","issue":"12","funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["National surveillance of Creutzfeldt-Jakob disease"],"award-info":[{"award-number":["National surveillance of Creutzfeldt-Jakob disease"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>The Glu to Lys change at codon 200 (E200K) of the <jats:italic>PRNP<\/jats:italic> gene is the most frequent mutation associated to genetic Creutzfeldt-Jakob disease (CJD) and the only one responsible for geographical clusters. Patients carrying this mutation develop disease at different ages and show variable clinical phenotypes that are not affected by the methione\/valine polymorphism at codon 129 of the <jats:italic>PRNP<\/jats:italic> gene suggesting the influence of other factors. The objective of this study is to look for genes other than <jats:italic>PRNP<\/jats:italic> that might be responsible of this variability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We searched for other genes by performing genome-wide analyses (GWA) on 19 patients with\u00a0genetic CJD and 18 healthy subjects carrying the E200K mutation of <jats:italic>PRNP<\/jats:italic> and belonging to the Calabrian cluster in Italy. We then validate this result in 32 patients with\u00a0E200K CJD from non-cluster areas and 259 patients with\u00a0sporadic CJD referred to the Italian CJD national registry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and conclusions<\/jats:title><jats:p>We identified two single nucleotide polymorphisms  on the  <jats:italic>CYP4X1<\/jats:italic>\u00a0gene locus as candidate disease modifiers in patients with\u00a0E200K CJD  of the cluster area and confirmed this finding in 32 patients with\u00a0E200K CJD  from non-cluster areas and 259 patients with\u00a0sporadic CJD.\u00a0Our results indicate that the <jats:italic>CYP4X1<\/jats:italic>\u00a0gene modulates the onset of disease in patients with\u00a0E200K genetic and sporadic CJD. This finding improves our understanding on the pathogenesis of CJD, suggests new targets for developing novel therapeutic strategies and might be useful for the stratification of patients in future preventive treatment trials.<\/jats:p><\/jats:sec>","DOI":"10.1136\/jnnp-2018-318756","type":"journal-article","created":{"date-parts":[[2018,7,21]],"date-time":"2018-07-21T16:15:23Z","timestamp":1532189723000},"page":"1243-1249","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["Age at onset of genetic (E200K) and sporadic Creutzfeldt-Jakob diseases is modulated by the <i>CYP4X1<\/i> gene"],"prefix":"10.1136","volume":"89","author":[{"given":"Anna","family":"Poleggi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"van der Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Capellari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Puopolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Ladogana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"De Pascali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Lia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Formato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Bartoletti-Stella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9444-9524","authenticated-orcid":false,"given":"Piero","family":"Parchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"van Duijn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7269-2486","authenticated-orcid":false,"given":"Maurizio","family":"Pocchiari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2018,7,21]]},"reference":[{"key":"2020050722284946000_89.12.1243.1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000160117.56690.B2"},{"key":"2020050722284946000_89.12.1243.2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh249"},{"key":"2020050722284946000_89.12.1243.3","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-005-0020-1"},{"key":"2020050722284946000_89.12.1243.4","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1007\/BF00143120","article-title":"\"Clusters\" of CJD in Slovakia: the first statistically significant temporo-spatial accumulations of rural cases","volume":"7","author":"Mitrov\u00e1","year":"1991","journal-title":"Eur J Epidemiol"},{"key":"2020050722284946000_89.12.1243.5","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000160118.26865.11"},{"key":"2020050722284946000_89.12.1243.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)61335-9"},{"key":"2020050722284946000_89.12.1243.7","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1212\/WNL.41.9.1385","article-title":"The Libyan Creutzfeldt-Jakob disease focus in Israel: an epidemiologic evaluation","volume":"41","author":"Zilber","year":"1991","journal-title":"Neurology"},{"key":"2020050722284946000_89.12.1243.8","doi-asserted-by":"crossref","unstructured":"Pocchiari M , Poleggi A , Puopolo M , et al . 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