{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:24:32Z","timestamp":1790778272891,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,4,14]],"date-time":"2024-04-14T00:00:00Z","timestamp":1713052800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FOR 2488"],"award-info":[{"award-number":["FOR 2488"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014381","name":"Peter und Traudl Engelhorn Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014381","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":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>X\u2010Linked dystonia\u2010parkinsonism (XDP) is an adult\u2010onset neurodegenerative disorder characterized by rapidly progressive dystonia and parkinsonism. Mosaic Divergent Repeat Interruptions affecting motif Length and Sequence (mDRILS) were recently found within the <jats:italic>TAF1<\/jats:italic> SVA repeat tract and were shown to associate with repeat stability and age at onset in XDP, specifically the AGGG [5\u2032\u2010SINE\u2010VNTR\u2010Alu(<jats:italic>AGAGGG<\/jats:italic>)<jats:sub>2<\/jats:sub><jats:italic>AGGG<\/jats:italic>(<jats:italic>AGAGGG<\/jats:italic>)<jats:sub>n<\/jats:sub>] mDRILS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to investigate the stability of mDRILS frequencies and stability of (<jats:italic>AGAGGG<\/jats:italic>)<jats:sub>n<\/jats:sub> repeat length during transmission in parent\u2013offspring pairs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fifty\u2010six families (n\u2009=\u2009130) were investigated for generational transmission of repeat length and mDRILS. The mDRILS stability of 16 individuals was assessed at two sampling points 1\u2009year apart. DNA was sequenced with long\u2010read technologies after long\u2010range polymerase chain reaction amplification of the <jats:italic>TAF1<\/jats:italic> SVA. Repeat number and mDRILS were detected with Noise\u2010Cancelling Repeat Finder (NCRF).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>When comparing the repeat domain, 51 of 65 children had either contractions or expansions of the repeat length. The AGGG frequency remained stable across generations at 0.074 (IQR: 0.069\u20130.078) (<jats:italic>z<\/jats:italic>\u2009=\u2009\u22120.526; <jats:italic>P<\/jats:italic>\u2009=\u20090.599). However, the median AGGG frequency in children with an expansion (0.072 [IQR: 0.066\u20130.076]) was lower compared with children with retention or contraction (0.080 [IQR: 0.073\u20130.083]) (<jats:italic>z<\/jats:italic>\u2009=\u2009\u22120.007; <jats:italic>P<\/jats:italic>\u2009=\u20090.003). In a logistic regression model, the AGGG frequency predicted the outcome of either expansion or retention\/contraction when including repeat number and sex as covariates (\u03b2\u2009=\u200980.7; <jats:italic>z<\/jats:italic>\u2010score\u2009=\u20092.63; <jats:italic>P<\/jats:italic>\u2009=\u20090.0085). The AGGG frequency varied slightly over 1\u2009year (0.070 [IQR: 0.063\u20130.080] to 0.073 [IQR: 0.069\u20130.078]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results show that a higher AGGG frequency may stabilize repeats across generations. This highlights the importance of further investigating mDRILS as a disease\u2010modifying factor with generational differences. \u00a9 2024 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29809","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T01:11:21Z","timestamp":1713143481000},"page":"1145-1153","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Stability of Mosaic Divergent Repeat Interruptions in X\u2010Linked Dystonia\u2010Parkinsonism"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2422-8486","authenticated-orcid":false,"given":"Joshua","family":"La\u00df","sequence":"first","affiliation":[{"name":"Institute of Neurogenetics, University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"L\u00fcth","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Schl\u00fcter","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, 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":"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":"Christoph","family":"Much","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5317-7369","authenticated-orcid":false,"given":"Roland Dominic","family":"Jamora","sequence":"additional","affiliation":[{"name":"Department of Neurosciences College of Medicine\u2010Philippine General Hospital, University of the Philippines Manila  Manila Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond L.","family":"Rosales","sequence":"additional","affiliation":[{"name":"Department of Neurology and Psychiatry University of Santo Tomas and the CNS\u2010Metropolitan Medical Center, Manila, Philippines Section of Neurology  Manila Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8322-4226","authenticated-orcid":false,"given":"Gerard","family":"Saranza","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Chong Hua Hospital  Cebu Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cid Czarina E.","family":"Diesta","sequence":"additional","affiliation":[{"name":"Department of Neurosciences Movement Disorders Clinic, Makati Medical Center  Makati City Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E.","family":"Pearson","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics University of Toronto  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inke R.","family":"K\u00f6nig","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry and Statistics, University of L\u00fcbeck  L\u00fcbeck 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