{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:17:26Z","timestamp":1786976246265,"version":"build-2736575974"},"reference-count":14,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"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\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["1U54NS148312"],"award-info":[{"award-number":["1U54NS148312"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["5K08NS123552"],"award-info":[{"award-number":["5K08NS123552"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006823","name":"Boston Children's Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006823","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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Adaptor protein complex 4\u2013associated hereditary spastic paraplegia (AP\u20104\u2010HSP), a childhood\u2010onset neurogenetic disorder and frequent mimic of cerebral palsy, is caused by biallelic variants in the adaptor protein complex 4 (AP\u20104) subunit genes (\n                    <jats:italic>AP4B1<\/jats:italic>\n                    [for SPG47],\n                    <jats:italic>AP4M1<\/jats:italic>\n                    [for SPG50],\n                    <jats:italic>AP4E1<\/jats:italic>\n                    [for SPG51], and\n                    <jats:italic>AP4S1<\/jats:italic>\n                    [for SPG52]). Diagnosis is often confounded by variants of uncertain significance. We evaluated the ATG9A ratio, a measure of ATG9A mislocalization in patient\u2010derived fibroblasts, as a functional assay of AP\u20104 deficiency. In six of eight individuals with suspected AP\u20104\u2010HSP, the assay demonstrated loss of AP\u20104 function, establishing pathogenicity of novel variants. These findings support the ATG9A ratio as a clinically useful diagnostic tool for confirming AP\u20104\u2010HSP and aiding the classification of novel variants.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                    identifier: NCT06948019, NCT05518188, NCT06692712, NCT04712812\n                  <\/jats:p>","DOI":"10.1002\/acn3.70308","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T05:11:57Z","timestamp":1767676317000},"page":"834-839","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Diagnostic Utility of the\n                    <scp>ATG9A<\/scp>\n                    Ratio in\n                    <scp>AP<\/scp>\n                    \u20104\u2013Associated Hereditary Spastic Paraplegia"],"prefix":"10.1002","volume":"13","author":[{"given":"Habibah A. P.","family":"Agianda","sequence":"first","affiliation":[{"name":"Movement Disorders Program, Department of Neurology and F.M. Kirby Neurobiology Center Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo\u2010Min","family":"Kim","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology and F.M. Kirby Neurobiology Center Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Battaglia","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology and F.M. Kirby Neurobiology Center Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Rong","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology and F.M. Kirby Neurobiology Center Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 and F.M. Kirby Neurobiology Center Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0031-2756","authenticated-orcid":false,"given":"Enrique","family":"Gonzalez Saez\u2010Diez","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology and F.M. Kirby Neurobiology Center Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius F.","family":"Boerkoel","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afshin","family":"Saffari","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Metabolic Medicine, Department of Pediatrics I, Medical Faculty Heidelberg, Center for Pediatrics and Adolescent Medicine University Hospital Heidelberg, Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Quiroz","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology and F.M. Kirby Neurobiology Center Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Schierbaum","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology and F.M. Kirby Neurobiology Center Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zainab","family":"Zaman","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology and F.M. Kirby Neurobiology Center Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Bernardi","sequence":"additional","affiliation":[{"name":"Movement Disorders Program, Department of Neurology and F.M. Kirby Neurobiology Center Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 and F.M. Kirby Neurobiology Center Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"Spastic Paraplegia \u2013 Centers of Excellence Research Network (SP\u2010CERN), Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012836"},{"issue":"10","key":"e_1_2_10_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"},{"key":"e_1_2_10_4_1","volume-title":"GeneReviews","author":"Alecu J.","year":"2025"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz310"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28609-w"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06172-7"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-44264-1"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44321-024-00148-5"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E19-11-0658"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1615302"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007363"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI164575"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcab221"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03078-4"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.70308","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acn3.70308","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.70308","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:16:58Z","timestamp":1776053818000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.70308"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,5]]},"references-count":14,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/acn3.70308"],"URL":"https:\/\/doi.org\/10.1002\/acn3.70308","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,5]]},"assertion":[{"value":"2025-10-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}