{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:36:01Z","timestamp":1790444161533,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,8,28]],"date-time":"2018-08-28T00:00:00Z","timestamp":1535414400000},"content-version":"vor","delay-in-days":58,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"DFG","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\/501100003390","name":"Fritz Thyssen Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003390","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    The most likely genetic cause of X\u2010linked dystonia\u2010parkinsonism, a neurodegenerative movement disorder endemic to the Philippines, is a 2672\u2010bp\u2010long retrotransposon insertion in intron 32 of the\n                    <jats:italic>TAF1<\/jats:italic>\n                    gene. The objectives of this study were to investigate whether (1)\n                    <jats:italic>TAF1<\/jats:italic>\n                    expression is altered in induced pluripotent stem cells and differentiated neuronal models and (2) excision of the retrotransposon insertion restores normal\n                    <jats:italic>TAF1<\/jats:italic>\n                    expression.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Expression of\n                    <jats:italic>TAF1<\/jats:italic>\n                    and its neuronal isoform were determined in induced pluripotent stem cells and in induced pluripotent stem cell\u2010derived cortical neurons and spiny projection neurons using quantitative PCR. Genome editing\u2010based excision of the retrotransposon insertion was performed on induced pluripotent stem cells from 3 X\u2010linked dystonia\u2010parkinsonism patients. Edited and unedited induced pluripotent stem cells from X\u2010linked dystonia\u2010parkinsonism patients and controls were differentiated into cortical neurons and spiny projection neurons, and\n                    <jats:italic>TAF1<\/jats:italic>\n                    expression was compared across groups.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    <jats:italic>TAF1<\/jats:italic>\n                    was reduced in patient\u2010derived induced pluripotent stem cells (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05) and spiny projection neurons (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.01). After genome editing, we observed higher\n                    <jats:italic>TAF1<\/jats:italic>\n                    expression in edited compared with unedited induced pluripotent stem cells (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.0001). In edited spiny projection neurons,\n                    <jats:italic>TAF1<\/jats:italic>\n                    expression was also increased, but did not reach statistical significance. No expression differences were observed in cortical neurons.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    (1)\n                    <jats:italic>TAF1<\/jats:italic>\n                    reduction in X\u2010linked dystonia\u2010parkinsonism is likely due to the retrotransposon insertion and is recapitulated in induced pluripotent stem cells and differentiated spiny projection neurons. (2)\n                    <jats:italic>TAF1<\/jats:italic>\n                    reduction is a tractable molecular phenotype of X\u2010linked dystonia\u2010parkinsonism that can be driven by excision of the retrotransposon insertion. (3) Successful rescue of the molecular phenotype in an endogenous, genome\u2010edited model serves as a proof of principle that may successfully be transferred to other inherited neurodegenerative diseases. \u00a9 2018 International Parkinson and Movement Disorder Society\n                  <\/jats:p>","DOI":"10.1002\/mds.27441","type":"journal-article","created":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T01:09:17Z","timestamp":1535591357000},"page":"1108-1118","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Genome editing in induced pluripotent stem cells rescues\n                    <i>TAF1<\/i>\n                    levels in X\u2010linked dystonia\u2010parkinsonism"],"prefix":"10.1002","volume":"33","author":[{"given":"Aleksandar","family":"Rakovic","sequence":"first","affiliation":[{"name":"Institute of Neurogenetics 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Gr\u00fctz","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonora","family":"Kulikovskaja","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Capetian","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally A.","family":"Cowley","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology University of Oxford Oxford United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Insa","family":"Lenz","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5969-6899","authenticated-orcid":false,"given":"Norbert","family":"Br\u00fcggemann","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Rosales","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Psychiatry University of Santo Tomas Manila Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5317-7369","authenticated-orcid":false,"given":"Dominic","family":"Jamora","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, College of Medicine University of the Philippines\u2010Philippine General Hospital Manila Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt","family":"Rolfs","sequence":"additional","affiliation":[{"name":"Albrecht\u2010Kossel\u2010Institute for Neuroregeneration (AKos) University of Rostock Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Seibler","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Westenberger","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of 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