{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T10:05:00Z","timestamp":1789380300049,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82450115"],"award-info":[{"award-number":["82450115"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82330037"],"award-info":[{"award-number":["82330037"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neurodegenerative disorders are clinically and genetically heterogeneous, characterized by progressive neuronal loss and multidomain functional decline. Despite a presumed genetic etiology, a substantial proportion of cases remain molecularly undiagnosed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The aim was to identify the genetic cause of an early\u2010onset neurodegenerative disorder presenting with ataxia and cognitive impairment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Rare copy\u2010number variants were detected via short\u2010read whole\u2010genome sequencing (WGS), with candidate structural models inferred using long\u2010read WGS. We performed transcriptomic profiling of peripheral blood leukocytes by RNA sequencing, with validation using reverse transcription\u2013quantitative polymerase chain reaction (RT\u2010qPCR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified a de novo copy\u2010number gain at 16p13.3. Combined copy\u2010number profiling and long\u2010read WGS suggested a candidate model comprising a triplicated segment in tandem with a proximal duplication, joined to a distal duplication via an inverted junction. Transcriptomic analysis demonstrated significant upregulation of\n                      <jats:italic>ATP6V0C<\/jats:italic>\n                      ,\n                      <jats:italic>AMDHD2<\/jats:italic>\n                      , and\n                      <jats:italic>PDPK1<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings support a role for structural variation in early\u2010onset neurodegeneration and highlight the value of combining short\u2010read copy\u2010number profiling with long\u2010read WGS to detect and characterize complex genomic rearrangements. \u00a9 2026 International Parkinson and Movement Disorder Society.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70540","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:27:55Z","timestamp":1789378075000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A De Novo 16p13.3 Triplication Underlying Early\u2010Onset Complex Neurodegeneration"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6883-3226","authenticated-orcid":false,"given":"Ze\u2010Hong","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Neurology, Fujian Institute of Neurology The First Affiliated Hospital, Fujian Medical University  Fuzhou China"},{"name":"Department of Rare Diseases, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University  Fuzhou China"},{"name":"Fujian Key Laboratory of Molecular Neurology, Institute of Neuroscience Fujian Medical University  Fuzhou 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