{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T20:50:28Z","timestamp":1771015828363,"version":"3.50.1"},"reference-count":18,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP22K15646"],"award-info":[{"award-number":["JP22K15646"]}],"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":["JP23K27520"],"award-info":[{"award-number":["JP23K27520"]}],"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":["JP24K02230"],"award-info":[{"award-number":["JP24K02230"]}],"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":["JP24K10637"],"award-info":[{"award-number":["JP24K10637"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["JPMH23FC1010"],"award-info":[{"award-number":["JPMH23FC1010"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP23dk0207066h0001"],"award-info":[{"award-number":["JP23dk0207066h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24dk0207066h0002"],"award-info":[{"award-number":["JP24dk0207066h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24ek0109617"],"award-info":[{"award-number":["JP24ek0109617"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24ek0109648"],"award-info":[{"award-number":["JP24ek0109648"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24ek0109674"],"award-info":[{"award-number":["JP24ek0109674"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24ek0109677"],"award-info":[{"award-number":["JP24ek0109677"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24ek0109760"],"award-info":[{"award-number":["JP24ek0109760"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Heterozygous variants of sequestosome\u20101 gene (<jats:italic>SQSTM1<\/jats:italic>) have been reported in patients with various neurological disorders, whereas biallelic pathogenic variants of <jats:italic>SQSTM1<\/jats:italic> can cause child\u2010onset and multisystem neurodegeneration, including cerebellar ataxia, dystonia, and vertical gaze palsy (NADGP). Here, we describe two cases of NADGP in a Japanese family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed clinical and genetic laboratory evaluations of the two patients and their healthy parents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>By whole\u2010exome sequencing, we identified compound heterozygous variants in <jats:italic>SQSTM1<\/jats:italic>(NM_003900.5): c.1A&gt;G p.(Met1?) in the initial codon, and c.969G&gt;A, located at the 3\u2032 end of exon 6, which is novel and seemingly a synonymous but is actually a truncating variant causing aberrant splicing. An SQSTM1 protein expression assay using urine\u2010derived cells (UDCs) demonstrated that both variants (c.1A&gt;G and c.969G&gt;A) were unable to induce normal splicing of premessenger RNA. Cerebellar ataxia is a characteristic manifestation of this disorder; however, brain magnetic resonance imaging studies have not shown significant cerebellar atrophy. Our patients experienced chorea during adolescence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Only a few reports have highlighted the presence of chorea; however, our findings suggest that NADGP should be considered as a differential diagnosis of hereditary chorea. This study also demonstrates the utility of UDCs, obtained using noninvasive approaches, in functionally analyzing genetic diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70044","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T06:38:51Z","timestamp":1732603131000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Novel Synonymous Variant in <i>SQSTM1<\/i> Causes Neurodegeneration With Ataxia, Dystonia, and Gaze Palsy Revealed by Urine\u2010Derived Cells\u2010Based Functional Analysis"],"prefix":"10.1002","volume":"12","author":[{"given":"Shinji","family":"Masuko","sequence":"first","affiliation":[{"name":"Department of Medicine (Neurology &amp; Rheumatology) Shinshu University School of Medicine  Matsumoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuto","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology &amp; Rheumatology) Shinshu University School of Medicine  Matsumoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2342-1089","authenticated-orcid":false,"given":"Katsuya","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology &amp; Rheumatology) Shinshu University School of Medicine  Matsumoto Japan"},{"name":"Center for Medical Genetics Shinshu University Hospital  Matsumoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kohei","family":"Hamanaka","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoko","family":"Miyatake","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Inaba","sequence":"additional","affiliation":[{"name":"Division of Neuropediatrics Nagano Children's Hospital  Azumino Japan"},{"name":"Life Science Research Center, Nagano Children's Hospital  Azumino Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8344-7507","authenticated-orcid":false,"given":"Tomoki","family":"Kosho","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Shinshu University Hospital  Matsumoto Japan"},{"name":"Department of Medical Genetics Shinshu University School of Medicine  Matsumoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9846-6500","authenticated-orcid":false,"given":"Naomichi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiki","family":"Sekijima","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology &amp; Rheumatology) Shinshu University School of Medicine  Matsumoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000001864"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.14025"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8050627"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.716471"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.06.026"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0b013e31827f0fe5"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2021.06.001"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1042\/EBC20170035"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/340731"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005869"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13104\u2010015\u20101686\u20107"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201029240\u2010w"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3791\/60840"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.12.2581"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/13816810.2019.1666414"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864\u2010017\u20103671\u20100"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2017.4791"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2018.12.031"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70044","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T07:00:13Z","timestamp":1732690813000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.70044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":18,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1002\/mgg3.70044"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.70044","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11]]},"assertion":[{"value":"2024-07-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70044"}}