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Most reported patients involve single-nucleotide variants, whereas copy number variants (CNVs) have been described only once in the PubMed-listed literature. The therapeutic potential of deep-brain stimulation (DBS) in\n                    <jats:italic>KIF1C<\/jats:italic>\n                    -related disease has not yet been evaluated.\u00a0We report a patient presenting with spasticity, ataxia, dystonia, and head tremor, in whom prior exome sequencing was inconclusive. A multi-omics approach was applied, including optical genome mapping (OGM), genome sequencing, and transcriptome sequencing. The clinical effect of DBS was assessed.\u00a0OGM revealed a homozygous\n                    <jats:italic>KIF1C<\/jats:italic>\n                    Exon 17\u201318 deletion, retrospectively detectable in exome and genome data but initially missed by sequence analysis. Transcriptome sequencing demonstrated significantly reduced\n                    <jats:italic>KIF1C<\/jats:italic>\n                    expression and absence of normally spliced transcripts around those exons, consistent with a loss-of-function mechanism. DBS led to partial clinical improvement, with notable reduction of dystonia and head tremor.\u00a0Structural variants may be an underrecognized cause of complex movement disorders involving spasticity, ataxia, and dystonia. Diagnostic methods specifically targeting structural variation, such as OGM or CNV analysis of short-read data, can be essential for diagnosis. Transcriptome data add valuable functional insight. This report also suggests that DBS may offer symptomatic benefit in\n                    <jats:italic>KIF1C<\/jats:italic>\n                    -associated disease, particularly for dystonic signs.\n                  <\/jats:p>","DOI":"10.1007\/s12311-026-01963-x","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T07:33:15Z","timestamp":1774337595000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multi-Omics Characterization of a KIF1C Structural Variant in a Patient with a Complex Movement Disorder Partially Responsive to Deep Brain Stimulation"],"prefix":"10.1007","volume":"25","author":[{"given":"Mirja","family":"Thomsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Borsche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente A.","family":"Y\u00e9pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Rasche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian K.","family":"Ullrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Tadic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad M.","family":"Abdelwakeel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hauke","family":"Busch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f6ren","family":"Franzenburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Trinh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Lohmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Br\u00fcggemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"issue":"6","key":"1963_CR1","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/s41576-023-00683-w","volume":"25","author":"KD Kernohan","year":"2024","unstructured":"Kernohan KD, Boycott KM. The expanding diagnostic toolbox for rare genetic diseases. Nat Rev Genet. 2024;25(6):401\u201315. https:\/\/doi.org\/10.1038\/s41576-023-00683-w.","journal-title":"Nat Rev Genet"},{"issue":"12","key":"1963_CR2","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1038\/s41431-020-0675-z","volume":"28","author":"JM Moreno-Cabrera","year":"2020","unstructured":"Moreno-Cabrera JM, Del Valle J, Castellanos E, et al. Evaluation of CNV detection tools for NGS panel data in genetic diagnostics. Eur J Hum Genet. 2020;28(12):1645\u201355. https:\/\/doi.org\/10.1038\/s41431-020-0675-z.","journal-title":"Eur J Hum Genet"},{"key":"1963_CR3","doi-asserted-by":"publisher","first-page":"103174","DOI":"10.1016\/j.jbi.2019.103174","volume":"94","author":"W Whitford","year":"2019","unstructured":"Whitford W, Lehnert K, Snell RG, Jacobsen JC. Evaluation of the performance of copy number variant prediction tools for the detection of deletions from whole genome sequencing data. J Biomed Inf. 2019;94:103174. https:\/\/doi.org\/10.1016\/j.jbi.2019.103174.","journal-title":"J Biomed Inf"},{"issue":"12","key":"1963_CR4","doi-asserted-by":"publisher","first-page":"1958","DOI":"10.3390\/genes12121958","volume":"12","author":"P Dremsek","year":"2021","unstructured":"Dremsek P, Schwarz T, Weil B, Malashka A, Laccone F, Neesen J. Optical genome mapping in routine human genetic Diagnostics-Its advantages and limitations. Genes (Basel). 2021;12(12):1958. https:\/\/doi.org\/10.3390\/genes12121958.","journal-title":"Genes (Basel)"},{"issue":"3","key":"1963_CR5","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1002\/mds.26944","volume":"32","author":"M Synofzik","year":"2017","unstructured":"Synofzik M, Sch\u00fcle R. Overcoming the divide between ataxias and spastic paraplegias: shared phenotypes, genes, and pathways. 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C.K. is a consultant for Centogene and Biogen and received speakers\u2019 honoraria from Bial and royalties from Oxford University Press and Springer Nature.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Financial Disclosures"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"41"}}