{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:50:29Z","timestamp":1791395429875,"version":"4.3.3"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Although many individuals with dystonia present with features indicative of single\u2010gene etiologies, obtaining definitive genetic diagnoses can be challenging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We assessed the value of nanopore\u2010based long\u2010read sequencing (LRS) in achieving molecular clarification of dystonic syndromes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>From a large dystonia cohort with short\u2010read sequencing (SRS) data, 14 cases with unclear, difficult\u2010to\u2010evaluate, or missing causative variants were recruited. Long\u2010read whole\u2010genome sequencing was performed according to Oxford Nanopore Technologies (ONT) protocols.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ONT sequencing produced long\u2010range haplotypes, variant calls inaccessible to short\u2010read technology, as well as methylation data. Phase inference allowed for changes in variant classification, establishing compound heterozygosity of causative variants in four cases. We illustrate an important advantage of LRS compared with SRS in (re)defining the identity of dystonia\u2010causing structural variants and repeat expansions for seven individuals. One patient was found to harbor a novel exonic LINE\u20101 insertion in\n                      <jats:italic>SGCE<\/jats:italic>\n                      , expanding the genetic mechanism in myoclonus\u2010dystonia. ONT data also provided unexpected insights into apparent mosaic expanded repeats in\n                      <jats:italic>FMR1<\/jats:italic>\n                      in a subject with isolated focal dystonia. We further showed that LRS outperformed SRS in avoiding erroneous calls resulting from confounding pseudogene sequences and in discovering pathogenic alterations missed by conventional pipeline utilization (three cases). Moreover, simultaneous methylome analysis aided in directing the interpretation of three variants, including a\n                      <jats:italic>KMT2B<\/jats:italic>\n                      variant of uncertain significance that was reclassified as causal by LRS\u2010based episignature profiling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      ONT\u2010based LRS uniquely improves analysis of dystonia\u2010associated variations that had not previously been resolved by SRS, implying broad utility for future exploration of the molecular origins of the condition. \u00a9 2025 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70072","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T04:30:39Z","timestamp":1759293039000},"page":"70-83","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Integrating Long\u2010Read Nanopore Sequencing for Precision Resolution of Genomic Variants in Dystonia"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8139-6198","authenticated-orcid":false,"given":"Ugo","family":"Sorrentino","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, School of Medicine and Health Technical University of Munich  Munich Germany"},{"name":"Institute of Neurogenomics Helmholtz Zentrum M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Pavlov","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine and Health 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