{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:29:06Z","timestamp":1790630946486,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020692","name":"Memphis Research Consortium","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020692","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":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spinocerebellar ataxia type 4 (SCA4) is an autosomal dominant ataxia with invariable sensory neuropathy originally described in a family with Swedish ancestry residing in Utah more than 25\u2009years ago. Despite tight linkage to the 16q22 region, the molecular diagnosis has since remained elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Inspired by pathogenic structural variation implicated in other 16q\u2010ataxias with linkage to the same locus, we revisited the index SCA4 cases from the Utah family using novel technologies to investigate structural variation within the candidate region.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We adopted a targeted long\u2010read sequencing approach with adaptive sampling on the Oxford Nanopore Technologies (ONT) platform that enables the detection of segregating structural variants within a genomic region without\n                      <jats:italic>a priori<\/jats:italic>\n                      assumptions about any variant features.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Using this approach, we found a heterozygous (GGC)\n                      <jats:sub>n<\/jats:sub>\n                      repeat expansion in the last coding exon of the zinc finger homeobox 3 (\n                      <jats:italic>ZFHX3<\/jats:italic>\n                      ) gene that segregates with disease, ranging between 48 and 57 GGC repeats in affected probands. This finding was replicated in a separate family with SCA4. Furthermore, the estimation of this GGC repeat size in short\u2010read whole genome sequencing (WGS) data of 21,836 individuals recruited to the 100,000 Genomes Project in the UK and our in\u2010house dataset of 11,258 exomes did not reveal any pathogenic repeats, indicating that the variant is ultrarare.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings support the utility of adaptive long\u2010read sequencing as a powerful tool to decipher causative structural variation in unsolved cases of inherited neurological disease. \u00a9 2024 The Authors.\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.29704","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T03:38:45Z","timestamp":1704857925000},"page":"486-497","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Adaptive Long\u2010Read Sequencing Reveals\n                    <scp>GGC<\/scp>\n                    Repeat Expansion in\n                    <scp>\n                      <i>ZFHX3<\/i>\n                    <\/scp>\n                    Associated with Spinocerebellar Ataxia Type 4"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6668-7202","authenticated-orcid":false,"given":"Zhongbo","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurodegenerative Disease Queen Square Institute of Neurology, University College London  London United Kingdom"},{"name":"Department of Genetics and Genomic Medicine Great Ormond Street Institute of Child Health, University College London  London United Kingdom"},{"name":"NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil K.","family":"Gustavsson","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Medicine Great Ormond Street Institute of Child Health, University College London  London United Kingdom"},{"name":"NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Macpherson","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease Queen Square Institute of Neurology, University College London  London United Kingdom"},{"name":"Department of Genetics and Genomic Medicine Great Ormond Street Institute of Child Health, University College London  London 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