{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T16:15:59Z","timestamp":1786637759449,"version":"build-2736575974"},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["RN127580\u2010260005"],"award-info":[{"award-number":["RN127580\u2010260005"]}],"id":[{"id":"10.13039\/501100000024","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":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Hereditary spastic paraplegias (HSPs) are neurodegenerative disorders characterized by lower\u2010limb spasticity. Pathogenic variants in\n                      <jats:italic>CPT1C<\/jats:italic>\n                      have been implicated in HSP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      The objective of this study was to assess whether\n                      <jats:italic>CPT1C<\/jats:italic>\n                      loss\u2010of\u2010function (LOF) variants are causally associated with HSP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed whole\u2010genome sequencing data from UK Biobank (UKBB), whole\u2010exome sequencing data from a Canadian HSP cohort (Can\u2010HSP), and genetic data from the GENESIS cohort\u2014a large international cohort of patients with rare hereditary diseases, including HSP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among &gt;170\n                      <jats:italic>CPT1C<\/jats:italic>\n                      LOF carriers in the UKBB (n\u2009=\u2009150,119), none exhibited HSP phenotypes. Among 585 HSP patients from Can\u2010HSP, we did not find patients with\n                      <jats:italic>CPT1C<\/jats:italic>\n                      LOF variants. In the GENESIS cohort (n\u2009=\u200921,217), three individuals carrying\n                      <jats:italic>CPT1C<\/jats:italic>\n                      LOF variants were also diagnosed with HSP; however, all three also carry pathogenic variants in established HSP\u2010associated genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study does not support a causal role for\n                      <jats:italic>CPT1C<\/jats:italic>\n                      LOF variants in HSP. \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.70144","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T10:06:58Z","timestamp":1764324418000},"page":"779-784","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Loss\u2010of\u2010Function Variants in\n                    <scp>\n                      <i>CPT1C<\/i>\n                    <\/scp>\n                    : No Support for a Causal Role in Hereditary Spastic Paraplegia"],"prefix":"10.1002","volume":"41","author":[{"given":"Rui","family":"Zhu","sequence":"first","affiliation":[{"name":"The Neuro (Montreal Neurological Institute\u2010Hospital), McGill University  Montreal Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lang","family":"Liu","sequence":"additional","affiliation":[{"name":"The Neuro (Montreal Neurological Institute\u2010Hospital), McGill University  Montreal Qu\u00e9bec Canada"},{"name":"Department of Human Genetics McGill University  Montreal Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehrdad A.","family":"Estiar","sequence":"additional","affiliation":[{"name":"The Neuro (Montreal Neurological Institute\u2010Hospital), McGill University  Montreal Qu\u00e9bec Canada"},{"name":"Department of Human Genetics McGill University  Montreal Qu\u00e9bec Canada"},{"name":"Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farnaz","family":"Asayesh","sequence":"additional","affiliation":[{"name":"The Neuro (Montreal Neurological Institute\u2010Hospital), McGill University  Montreal Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamil","family":"Ahmad","sequence":"additional","affiliation":[{"name":"The Neuro (Montreal Neurological Institute\u2010Hospital), McGill University  Montreal Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meron","family":"Teferra","sequence":"additional","affiliation":[{"name":"The Neuro (Montreal Neurological Institute\u2010Hospital), McGill University  Montreal Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Yoon","sequence":"additional","affiliation":[{"name":"Divisions of Neurology and Clinical and Metabolic Genetics, Department of Paediatrics University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Tarnopolsky","sequence":"additional","affiliation":[{"name":"Department of Pediatrics McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kym M.","family":"Boycott","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Dupre","sequence":"additional","affiliation":[{"name":"Neuroscience Axis, CHU de Qu\u00e9bec Universit\u00e9 Laval  Qu\u00e9bec City Qu\u00e9bec Canada"},{"name":"Department of Medicine, Faculty of Medicine Universit\u00e9 Laval  Qu\u00e9bec City Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick A.","family":"Dion","sequence":"additional","affiliation":[{"name":"The Neuro (Montreal Neurological Institute\u2010Hospital), McGill University  Montreal Qu\u00e9bec Canada"},{"name":"Department of Human Genetics McGill University  Montreal Qu\u00e9bec Canada"},{"name":"Department of Neurology and Neurosurgery McGill University  Montreal Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oksana","family":"Suchowersky","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology) and Medical Genetics University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albena","family":"Jordanova","sequence":"additional","affiliation":[{"name":"Molecular Neurogenomics Group, VIB Center for Molecular Neurology, VIB  Antwerp Belgium"},{"name":"Molecular Neurogenomics Group, Department of Biomedical Sciences University of Antwerp  Antwerp Belgium"},{"name":"Department of Medical Chemistry and Biochemistry Medical University\u2010Sofia  Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0102-164X","authenticated-orcid":false,"given":"Yi\u2010Chung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Department of Neurology National Yang\u2010Ming University School of Medicine  Taipei Taiwan"},{"name":"Brain Research Center, National Yang\u2010Ming University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9368-8657","authenticated-orcid":false,"given":"Giovanni","family":"Stevanin","sequence":"additional","affiliation":[{"name":"University of Bordeaux INCIA, UMR5287, CNRS, EPHE  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Zuchner","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics University of Miami Miller School of Medicine  Miami Florida USA"},{"name":"John P. Hussman Institute for Human Genomics University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8403-1418","authenticated-orcid":false,"given":"Guy A.","family":"Rouleau","sequence":"additional","affiliation":[{"name":"The Neuro (Montreal Neurological Institute\u2010Hospital), McGill University  Montreal Qu\u00e9bec Canada"},{"name":"Department of Human Genetics McGill University  Montreal Qu\u00e9bec Canada"},{"name":"Department of Neurology and Neurosurgery McGill University  Montreal Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0332-234X","authenticated-orcid":false,"given":"Ziv","family":"Gan\u2010Or","sequence":"additional","affiliation":[{"name":"The Neuro (Montreal Neurological Institute\u2010Hospital), McGill University  Montreal Qu\u00e9bec Canada"},{"name":"Department of Human Genetics McGill University  Montreal Qu\u00e9bec Canada"},{"name":"Department of Neurology and Neurosurgery McGill University  Montreal Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70258-8"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-020-04981-7"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2009.01176.x"},{"key":"e_1_2_9_5_1","volume-title":"GeneReviews(\u00ae)","author":"Hedera P","year":"1993"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.4769"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.717"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.15385"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.52288"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2025.107946"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2015.11.004"},{"key":"e_1_2_9_12_1","doi-asserted-by":"crossref","unstructured":"EstiarMA YuE SalemIH et al.Evidence for non\u2010mendelian inheritance in spastic paraplegia 7. medRxiv 2020:2020.2009.2025.20176032.","DOI":"10.1101\/2020.09.25.20176032"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2024.114978"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04965-x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0974-4"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.03.004"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1071"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000244413.49258.f5"}],"updated-by":[{"DOI":"10.1002\/mds.70320","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000}}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70144","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mds.70144","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T15:17:15Z","timestamp":1786634235000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.70144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,28]]},"references-count":19,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/mds.70144"],"URL":"https:\/\/doi.org\/10.1002\/mds.70144","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,28]]},"assertion":[{"value":"2025-09-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}