{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:36:08Z","timestamp":1790444168284,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T00:00:00Z","timestamp":1600992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>X\u2010linked dystonia\u2010parkinsonism is a rare neurological disease endemic to the Philippines. Dystonic symptoms appear in males at the mean age of 40\u2009years and progress to parkinsonism with degenerative pathology in the striatum. A retrotransposon inserted in intron 32 of the <jats:italic>TAF1<\/jats:italic> gene leads to alternative splicing in the region and a reduction of the full\u2010length mRNA transcript.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The objective of this study was to discover cell\u2010based and biofluid\u2010based biomarkers for X\u2010linked dystonia\u2010parkinsonism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>RNA from patient\u2010derived neural progenitor cells and their secreted extracellular vesicles were used to screen for dysregulation of <jats:italic>TAF1<\/jats:italic> expression. Droplet\u2010digital polymerase chain reaction was used to quantify the expression of <jats:italic>TAF1<\/jats:italic> mRNA fragments 5\u2032 and 3\u2032 to the retrotransposon insertion and the disease\u2010specific splice variant TAF1\u201032i in whole\u2010blood RNA. Plasma levels of neurofilament light chain were measured using single\u2010molecule array.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In neural progenitor cells and their extracellular vesicles, we confirmed that the <jats:italic>TAF1<\/jats:italic>\u20103\u2032\/5\u2032 ratio was lower in patient samples, whereas <jats:italic>TAF1<\/jats:italic>\u201032i expression is higher relative to controls. In whole\u2010blood RNA, both TAF1\u20103\u2032\/5\u2032 ratio and TAF1\u201032i expression can differentiate patient (n = 44) from control samples (n = 18) with high accuracy. Neurofilament light chain plasma levels were significantly elevated in patients (n = 43) compared with both carriers (n = 16) and controls (n = 21), with area under the curve of 0.79.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>TAF1<\/jats:italic> dysregulation in blood serves as a disease\u2010specific biomarker that could be used as a readout for monitoring therapies targeting <jats:italic>TAF1<\/jats:italic> splicing. Neurofilament light chain could be used in monitoring neurodegeneration and disease progression in patients. \u00a9 2020 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.28305","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T08:30:58Z","timestamp":1601022658000},"page":"206-215","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["<scp><i>TAF1<\/i><\/scp> Transcripts and Neurofilament Light Chain as Biomarkers for X\u2010linked Dystonia\u2010Parkinsonism"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6301-9903","authenticated-orcid":false,"given":"Jamal","family":"Al Ali","sequence":"first","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital and Harvard Medical 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