{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:10:45Z","timestamp":1789873845649,"version":"4.0.1"},"reference-count":17,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,15]],"date-time":"2020-01-15T00:00:00Z","timestamp":1579046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hereditary spastic paraplegias (HSP) are neurodegenerative disorders characterized by lower limb spasticity and weakness, with or without additional symptoms. Mutations in <jats:italic>ATP13A2,<\/jats:italic> known to cause Kufor\u2013Rakeb syndrome (KRS), have been recently implicated in HSP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010exome sequencing was done in a Canada\u2010wide HSP cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three additional patients with homozygous <jats:italic>ATP13A2<\/jats:italic> mutations were identified, representing 0.7% of all HSP families. Spastic paraplegia was the predominant feature, all patients suffered from psychiatric symptoms, and one patient had developed seizures. Of the identified mutations, c.2126G&gt;C;(p.[Arg709Thr]) is novel, c.2158G&gt;T;(p.[Gly720Trp]) has not been reported in ATP13A2\u2010related diseases, and c.2473_2474insAAdelC;p.[Leu825Asnfs*32]) has been previously reported in KRS but not in HSP. Structural analysis of the mutations suggested a disruptive effect, and enrichment analysis suggested the potential involvement of specific pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study suggests that in HSP patients with psychiatric symptoms, <jats:italic>ATP13A2<\/jats:italic> mutations should be suspected, especially if they also have extrapyramidal symptoms.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1052","type":"journal-article","created":{"date-parts":[[2020,1,15]],"date-time":"2020-01-15T17:23:50Z","timestamp":1579109030000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Clinical and genetic analysis of <i>ATP13A2<\/i> in hereditary spastic paraplegia expands the phenotype"],"prefix":"10.1002","volume":"8","author":[{"given":"Mehrdad A.","family":"Estiar","sequence":"first","affiliation":[{"name":"Department of Human Genetics McGill University Montr\u00e9al QC Canada"},{"name":"Montreal Neurological Institute and Hospital McGill University Montr\u00e9al QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Leveille","sequence":"additional","affiliation":[{"name":"Faculty of Medicine McGill University Montr\u00e9al QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Spiegelman","sequence":"additional","affiliation":[{"name":"Montreal Neurological Institute and Hospital McGill University Montr\u00e9al QC Canada"},{"name":"Department of Neurology and Neurosurgery McGill University Montr\u00e9al QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Dupre","sequence":"additional","affiliation":[{"name":"Department of Medicine Faculty of Medicine Universit\u00e9 Laval Quebec City QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Trempe","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Therapeutics McGill University Montr\u00e9al QC Canada"},{"name":"Centre for Structural Biology McGill University Montr\u00e9al QC Canada"}],"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":"Department of Human Genetics McGill University Montr\u00e9al QC Canada"},{"name":"Montreal Neurological Institute and Hospital McGill University Montr\u00e9al QC Canada"},{"name":"Department of Neurology and Neurosurgery McGill University Montr\u00e9al QC 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":"Department of Human Genetics McGill University Montr\u00e9al QC Canada"},{"name":"Montreal Neurological Institute and Hospital McGill University Montr\u00e9al QC Canada"},{"name":"Department of Neurology and Neurosurgery McGill University Montr\u00e9al QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000122"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx070"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2011.01745.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2019.05.025"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww307"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/342359"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1590\/0004-282x20170160"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.02.009"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww111"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22122"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv320"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26243"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1884"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr606"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz041"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-019-0203-9"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.42"}],"container-title":["Molecular Genetics &amp; 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