{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:30:23Z","timestamp":1790487023363,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,5,3]],"date-time":"2019-05-03T00:00:00Z","timestamp":1556841600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004049","name":"Katholischer Akademischer Ausl\u00e4nder-Dienst","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FOR2488"],"award-info":[{"award-number":["FOR2488"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 936"],"award-info":[{"award-number":["SFB 936"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      X\u2010linked dystonia parkinsonism (XDP) is a neurodegenerative movement disorder caused by a single mutation: SINE\u2010VNTR\u2010Alu (SVA) retrotransposon insertion in\n                      <jats:italic>TAF1<\/jats:italic>\n                      . Recently, a (CCCTCT)\n                      <jats:sub>n<\/jats:sub>\n                      repeat within the SVA insertion has been reported as an age\u2010at\u2010onset (AAO) modifier in XDP. Here we investigate the role of this hexanucleotide repeat in modifying expressivity of XDP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We genotyped the hexanucleotide repeat in 355 XDP patients and correlated the repeat number (RN) with AAO (n = 295), initial clinical manifestation (n = 294), site of dystonia onset (n = 238), disease severity (n = 28), and cognitive function (n = 15). Furthermore, we investigated i) repeat instability by segregation analysis and Southern blotting using postmortem brain samples from two affected individuals and ii) relative\n                      <jats:italic>TAF1<\/jats:italic>\n                      expression in blood RNA from 31 XDP patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      RN showed significant inverse correlations with AAO and with\n                      <jats:italic>TAF1<\/jats:italic>\n                      expression and a positive correlation with disease severity and cognitive dysfunction. Importantly, AAO (and not RN) was directly associated with whether dystonia or parkinsonism will manifest at onset. RN was lower in patients affected by mouth\/tongue dystonia compared with blepharospasm. RN was unstable across germline transmissions with an overall tendency to increase in length and exhibited somatic mosaicism in brain.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      The hexanucleotide repeat within the SVA insertion acts as a genetic modifier of disease expressivity in XDP. RN\u2010dependent\n                      <jats:italic>TAF1<\/jats:italic>\n                      repression and subsequent differences in\n                      <jats:italic>TAF1<\/jats:italic>\n                      mRNA levels in patients may be potentiated in the brain through somatic variability leading to the neurological phenotype.\n                      <jats:bold>ANN NEUROL 2019;85:812\u2013822.<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.25488","type":"journal-article","created":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T00:45:17Z","timestamp":1555029917000},"page":"812-822","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":95,"title":["A hexanucleotide repeat modifies expressivity of X\u2010linked dystonia parkinsonism"],"prefix":"10.1002","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8062-6959","authenticated-orcid":false,"given":"Ana","family":"Westenberger","sequence":"first","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles Jourdan","family":"Reyes","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Saranza","sequence":"additional","affiliation":[{"name":"Department of Neurosciences College of Medicine\u2010Philippine General Hospital, University of the Philippines  Manila Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerija","family":"Dobricic","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"L\u00fcbeck Interdisciplinary Platform for Genome Analytics Institutes of Neurogenetics and Cardiogenetics, University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrike","family":"Hanssen","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Department of Neurology University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aloysius","family":"Domingo","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Center for Genomic Medicine Massachusetts General Hospital  Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn\u2010Hergen","family":"Laabs","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry and Statistics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susen","family":"Schaake","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Pozojevic","sequence":"additional","affiliation":[{"name":"Section for Functional Genetics Institute for Human Genetics, University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandar","family":"Rakovic","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Gr\u00fctz","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck 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