{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T07:48:49Z","timestamp":1791791329552,"version":"4.3.4"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR001881"],"award-info":[{"award-number":["UL1TR001881"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["X01NS141718"],"award-info":[{"award-number":["X01NS141718"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R35NS127253"],"award-info":[{"award-number":["R35NS127253"]}],"id":[{"id":"10.13039\/100000065","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":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Spinocerebellar ataxia 4 (SCA4) is a late\u2010onset dominant ataxia with neuropathy caused by exonic GGC repeat expansion in the\n                      <jats:italic>ZFHX3<\/jats:italic>\n                      gene thought to originate from a Swedish founder event. The GC\u2010rich expansion is highly thermodynamically stable, posing challenges for standard clinical genetic testing methods. Development of a high\u2010throughput relatively inexpensive detection method would benefit both clinical diagnostic testing and large\u2010scale research applications.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Using a cost\u2010effective high\u2010throughput polymerase chain reaction (PCR) assay, we assessed the frequency of SCA4 repeat expansion in an undiagnosed US ataxia cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      Primers flanking the\n                      <jats:italic>ZFHX3<\/jats:italic>\n                      repeat region were used under optimized PCR conditions to assess for expanded GGC repeats in 687 undiagnosed ataxia patients. Repeat size was determined by fragment analysis and orthogonally confirmed with long\u2010read sequencing (Oxford Nanopore Technologies).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified pathogenic SCA4 expansions in three families with cerebellar ataxia and sensory\/autonomic neuropathy. The pathogenic alleles were confirmed to be of Swedish ancestry using comprehensive haplotype analysis of 14 single nucleotide polymorphisms (SNPs) previously associated with\n                      <jats:italic>ZFHX3<\/jats:italic>\n                      expansion. Two families carried all 14 SNPs, suggesting this may represent an ancestral haplotype. Utilizing a minimal haplotype present in all reported patients, we bioinformatically assessed 852 additional subjects, for a total of 1539 screened, but did not identify additional SCA4 patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Using a high\u2010throughput cost\u2010effective PCR assay, we identified three SCA4 families in a large US ataxia cohort. Haplotype analysis supports a common Swedish founder allele, consistent with previously reported SCA4 cases. SCA4 diagnostic testing is recommended for all patients of Swedish ancestry with undiagnosed ataxia. \u00a9 2026 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.70387","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T01:47:26Z","timestamp":1780537646000},"page":"2476-2489","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Frequency of\n                    <scp>\n                      <i>ZFHX3<\/i>\n                    <\/scp>\n                    \u2010Mediated Spinocerebellar Ataxia 4 in a US Undiagnosed Ataxia Cohort"],"prefix":"10.1002","volume":"41","author":[{"given":"Annie","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology David Geffen School of Medicine, University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udbhav","family":"Avadhani","sequence":"additional","affiliation":[{"name":"Department of Neurology David Geffen School of Medicine, University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathie","family":"Ngo","sequence":"additional","affiliation":[{"name":"Department of Neurology David Geffen School of Medicine, University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario I.","family":"Corona","sequence":"additional","affiliation":[{"name":"Department of Human Genetics David Geffen School of Medicine, University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George de V. Carvalho","family":"Neto","sequence":"additional","affiliation":[{"name":"Department of Human Genetics David Geffen School of Medicine, University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla P.","family":"Figueroa","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Undiagnosed Diseases Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Perlman","sequence":"additional","affiliation":[{"name":"Department of Neurology David Geffen School of Medicine, University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan M.","family":"Pulst","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley F.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Neurology David Geffen School of Medicine, University of California, Los Angeles  Los Angeles California USA"},{"name":"Department of Human Genetics David Geffen School of Medicine, University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darice","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Neurology David Geffen School of Medicine, University of California, Los Angeles  Los Angeles California USA"},{"name":"Clinical Neurogenomics Research Center, UCLA Department of Neurology David Geffen School of Medicine, University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent L.","family":"Fogel","sequence":"additional","affiliation":[{"name":"Department of Neurology David Geffen School of Medicine, University of California, Los Angeles  Los Angeles California USA"},{"name":"Department of Human Genetics David Geffen School of Medicine, University of California, Los Angeles  Los Angeles California USA"},{"name":"Clinical Neurogenomics Research Center, UCLA Department of Neurology David Geffen School of Medicine, University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29738"},{"issue":"2","key":"e_1_2_10_3_1","first-page":"392","article-title":"Autosomal dominant spinocerebellar ataxia with sensory axonal neuropathy (SCA4): clinical description and genetic localization to chromosome 16q22.1","volume":"59","author":"Flanigan K","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00702-005-0362-9"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/JOIM.13815"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.11.008"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41588-024-01719-5"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/MDS.29704"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00415-024-12600-0"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/MDS.30077"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/MDS.30242"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/JAMANEUROL.2014.1944"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/S12311-023-01537-1"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/HUMU.23946"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0672-1"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000200133"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/BIOINFORMATICS\/BTP324"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/HUMU.24382"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41587-023-02057-3"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/BIOINFORMATICS\/BTR509"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/BIOINFORMATICS\/BTP352"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/BIOINFORMATICS\/BTY191"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/BIOINFORMATICS\/BTAB705"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/BIOINFORMATICS\/BTAD311"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xhgg.2022.100146"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1754"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/g3journal\/jkae268"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/BIOINFORMATICS\/BTR330"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1525-1578(10)60594-6"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2017.130"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/BRAIN\/AWAF318"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70387","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mds.70387","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70387","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T07:25:52Z","timestamp":1791789952000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.70387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":30,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/mds.70387"],"URL":"https:\/\/doi.org\/10.1002\/mds.70387","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]},"assertion":[{"value":"2026-01-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}