{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T09:01:19Z","timestamp":1788080479372,"version":"build-2784847793"},"reference-count":43,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,11,5]],"date-time":"2023-11-05T00:00:00Z","timestamp":1699142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21ak0101112"],"award-info":[{"award-number":["21ak0101112"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K14966"],"award-info":[{"award-number":["17K14966"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K17047"],"award-info":[{"award-number":["19K17047"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21H04820"],"award-info":[{"award-number":["21H04820"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22H04925"],"award-info":[{"award-number":["22H04925"]}],"id":[{"id":"10.13039\/501100001691","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":[[2023,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Parkin RBR E3 ubiquitin\u2010protein ligase<\/jats:italic>\n (\n PRKN<\/jats:italic>\n ) mutations are the most common cause of young onset and autosomal recessive Parkinson's disease (PD).\n PRKN<\/jats:italic>\n is located in FRA6E, which is one of the common fragile sites in the human genome, making this region prone to structural variants. However, complex structural variants such as inversions of\n PRKN<\/jats:italic>\n are seldom reported, suggesting that there are potentially unrevealed complex pathogenic\n PRKN<\/jats:italic>\n structural variants.\n <\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n \n To identify complex structural variants in\n PRKN<\/jats:italic>\n using long\u2010read sequencing.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We investigated the genetic cause of monozygotic twins presenting with a young onset dystonia\u2010parkinsonism using targeted sequencing, whole exome sequencing, multiple ligation probe amplification, and long\u2010read sequencing. We assessed the presence and frequency of complex inversions overlapping\n PRKN<\/jats:italic>\n using whole\u2010genome sequencing data of Accelerating Medicines Partnership Parkinson's disease (AMP\u2010PD) and United Kingdom (UK)\u2010Biobank datasets.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Multiple ligation probe amplification identified a heterozygous exon three deletion in\n PRKN<\/jats:italic>\n and long\u2010read sequencing identified a large novel inversion spanning over 7\u2009Mb, including a large part of the coding DNA sequence of\n PRKN<\/jats:italic>\n . We could diagnose the affected subjects as compound heterozygous carriers of\n PRKN<\/jats:italic>\n . We analyzed whole genome sequencing data of 43,538 participants of the UK\u2010Biobank and 4941 participants of the AMP\u2010PD datasets. Nine inversions in the UK\u2010Biobank and two in AMP PD were identified and were considered potentially damaging and likely to affect\n PRKN<\/jats:italic>\n expression.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n This is the first report describing a large 7\u2009Mb inversion involving breakpoints outside of\n PRKN<\/jats:italic>\n . This study highlights the importance of using long\u2010read sequencing for structural variant analysis in unresolved young\u2010onset PD cases. \u00a9 2023 The Authors.\n Movement Disorders<\/jats:italic>\n published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mds.29610","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T00:41:28Z","timestamp":1699231288000},"page":"2249-2257","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Long\u2010Read Sequencing Resolves a Complex Structural Variant in\n \n PRKN<\/i>\n <\/scp>\n Parkinson's Disease"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9177-9587","authenticated-orcid":false,"given":"Kensuke","family":"Daida","sequence":"first","affiliation":[{"name":"Integrative Neurogenomics Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health Bethesda Maryland USA"},{"name":"Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda Maryland USA"},{"name":"Department of Neurology, Faculty of Medicine Juntendo University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7412-3631","authenticated-orcid":false,"given":"Manabu","family":"Funayama","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine Juntendo University Tokyo Japan"},{"name":"Research Institute for Diseases of Old Age, Graduate School of Medicine Juntendo University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8003-4029","authenticated-orcid":false,"given":"Kimberley J.","family":"Billingsley","sequence":"additional","affiliation":[{"name":"Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laksh","family":"Malik","sequence":"additional","affiliation":[{"name":"Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Miano\u2010Burkhardt","sequence":"additional","affiliation":[{"name":"Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hampton L.","family":"Leonard","sequence":"additional","affiliation":[{"name":"Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda Maryland USA"},{"name":"Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health Bethesda Maryland USA"},{"name":"Data Tecnica International LLC Washington DC USA"},{"name":"German Center for Neurodegenerative Diseases (DZNE) T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7978-1051","authenticated-orcid":false,"given":"Mary B.","family":"Makarious","sequence":"additional","affiliation":[{"name":"Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health Bethesda Maryland USA"},{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology London United Kingdom"},{"name":"UCL Movement Disorders Centre University College London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8982-7885","authenticated-orcid":false,"given":"Hirotaka","family":"Iwaki","sequence":"additional","affiliation":[{"name":"Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health Bethesda Maryland USA"},{"name":"Data Tecnica International LLC Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhui","family":"Ding","sequence":"additional","affiliation":[{"name":"Computational Biology Group, Laboratory of Neurogenetics, National Institute on Aging, NIH, PorterNeuroscience Research Center Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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