{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T04:26:01Z","timestamp":1745987161477,"version":"3.40.4"},"reference-count":10,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017026","name":"Spastic Paraplegia Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008440","name":"International Parkinson and Movement Disorder Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Biallelic loss\u2010of\u2010function variants in <jats:italic>AP4S1<\/jats:italic> cause childhood\u2010onset hereditary spastic paraplegia. A recent report suggested that heterozygous <jats:italic>AP4S1<\/jats:italic> variants lead to a syndrome of lower limb spasticity and dysregulation of sphincter function. We critically evaluate this claim against clinical observations in 28 heterozygous carriers of the same <jats:italic>AP4S1<\/jats:italic> variant (NM_007077.3: c.289C&gt;T, p.Arg97Ter). In these 14 males and 14 females (mean age: 37.6\u2009\u00b1\u20094.9\u2009years [SD], range: 30\u201350\u2009years), we ascertain no increased prevalence of neurological manifestations. Alternative causes should be considered when evaluating patients with heterozygous <jats:italic>AP4S1<\/jats:italic> variants and neurological symptoms, as misattribution of pathogenicity can impact clinical care and genetic counseling.<\/jats:p>","DOI":"10.1002\/acn3.52302","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T08:39:14Z","timestamp":1737967154000},"page":"851-854","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Heterozygous variants in <scp><i>AP4S1<\/i><\/scp> are not associated with a neurological phenotype"],"prefix":"10.1002","volume":"12","author":[{"given":"Vicente","family":"Quiroz","sequence":"first","affiliation":[{"name":"Movement Disorders Program, Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Umar","family":"Zubair","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Schierbaum","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2072-3436","authenticated-orcid":false,"given":"Amy","family":"Tam","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Battaglia","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua","family":"Rong","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Habibah A. P.","family":"Agianda","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian E.","family":"Alecu","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Yang","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0026-4714","authenticated-orcid":false,"given":"Darius","family":"Ebrahimi\u2010Fakhari","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"volume-title":"GeneReviews\u00ae","year":"2018","author":"Ebrahimi\u2010Fakhari D","key":"e_1_2_9_2_1"},{"issue":"10","key":"e_1_2_9_3_1","first-page":"2929","article-title":"Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4\u2010associated hereditary spastic paraplegia","volume":"143","author":"Ebrahimi\u2010Fakhari D","year":"2020","journal-title":"Brain"},{"doi-asserted-by":"publisher","key":"e_1_2_9_4_1","DOI":"10.1212\/WNL.0000000000012836"},{"doi-asserted-by":"publisher","key":"e_1_2_9_5_1","DOI":"10.1093\/hmg\/ddz310"},{"doi-asserted-by":"publisher","key":"e_1_2_9_6_1","DOI":"10.1212\/NXG.0000000000200140"},{"doi-asserted-by":"publisher","key":"e_1_2_9_7_1","DOI":"10.1056\/NEJMsr1406261"},{"doi-asserted-by":"publisher","key":"e_1_2_9_8_1","DOI":"10.1038\/gim.2015.30"},{"doi-asserted-by":"publisher","key":"e_1_2_9_9_1","DOI":"10.1016\/j.ajhg.2018.06.009"},{"doi-asserted-by":"publisher","key":"e_1_2_9_10_1","DOI":"10.1002\/ana.24611"},{"doi-asserted-by":"publisher","key":"e_1_2_9_11_1","DOI":"10.1001\/jama.2018.14900"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.52302","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T02:15:08Z","timestamp":1745979308000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.52302"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,27]]},"references-count":10,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/acn3.52302"],"URL":"https:\/\/doi.org\/10.1002\/acn3.52302","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"type":"print","value":"2328-9503"},{"type":"electronic","value":"2328-9503"}],"subject":[],"published":{"date-parts":[[2025,1,27]]},"assertion":[{"value":"2024-10-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}