{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T12:38:49Z","timestamp":1786451929039,"version":"build-2736575974"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":73,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Institute of Health","award":["2023ER050602"],"award-info":[{"award-number":["2023ER050602"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hereditary spastic paraplegia (HSP) is a genetically neurodegenerative disorder with limited epidemiological data in Korea. This study aimed to characterize the genetic landscape of HSP in a large Korean cohort. We analyzed 657 patients with suspected HSP using Sanger sequencing and a targeted next-generation sequencing (NGS) panel covering 54 HSP-related genes. Variants were classified according to American College of Medical Genetics and Genomics\/Association for Molecular Pathology guidelines, and copy number variations (CNVs) were detected using in-house methods and multiplex ligation-dependent probe amplification. Pathogenic or likely pathogenic variants were identified in 121 patients (18%), with\n                    <jats:italic>SPAST<\/jats:italic>\n                    (83%) and\n                    <jats:italic>ATL1<\/jats:italic>\n                    (6%) being the most frequently mutated genes. Notably, 5% of\n                    <jats:italic>SPAST<\/jats:italic>\n                    mutations were CNVs, underscoring the importance of CNV detection. Among the identified variants, 23 novel mutations were discovered, primarily in\n                    <jats:italic>SPAST<\/jats:italic>\n                    (19),\n                    <jats:italic>REEP1<\/jats:italic>\n                    (3), and\n                    <jats:italic>SACS<\/jats:italic>\n                    (1), expanding the mutational spectrum of HSP. The diagnostic yield was higher with NGS (25%) compared to Sanger sequencing (16%), reflecting the panel\u2019s broader gene coverage. This study highlights the predominance of\n                    <jats:italic>SPAST<\/jats:italic>\n                    and\n                    <jats:italic>ATL1<\/jats:italic>\n                    mutations in Korean HSP patients and emphasizes the utility of targeted NGS panels, particularly for detecting CNVs and novel variants. Despite these advances, the majority of cases remain unresolved, suggesting the need for broader sequencing approaches to uncover additional genetic factors. These findings provide a foundation for improved diagnostic strategies and personalized treatment in HSP.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-53107-0","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T05:47:01Z","timestamp":1780292821000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic landscape of hereditary spastic paraplegias in the Korean population"],"prefix":"10.1038","volume":"16","author":[{"given":"Mi-Ae","family":"Jang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ja-Hyun","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byoung Joon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duk Hyun","family":"Sung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"53107_CR1","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1007\/s11910-019-0930-2","volume":"19","author":"M Boutry","year":"2019","unstructured":"Boutry, M., Morais, S. & Stevanin, G. Update on the genetics of spastic paraplegias. Curr. Neurol. Neurosci. Rep. 19, 18. https:\/\/doi.org\/10.1007\/s11910-019-0930-2 (2019).","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"53107_CR2","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1159\/000358801","volume":"42","author":"L Ruano","year":"2014","unstructured":"Ruano, L., Melo, C., Silva, M. C. & Coutinho, P. The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology 42, 174\u2013183. https:\/\/doi.org\/10.1159\/000358801 (2014).","journal-title":"Neuroepidemiology"},{"key":"53107_CR3","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.neurol.2015.02.017","volume":"171","author":"S Klebe","year":"2015","unstructured":"Klebe, S., Stevanin, G. & Depienne, C. Clinical and genetic heterogeneity in hereditary spastic paraplegias: from SPG1 to SPG72 and still counting. Rev. Neurol. (Paris). 171, 505\u2013530. https:\/\/doi.org\/10.1016\/j.neurol.2015.02.017 (2015).","journal-title":"Rev. Neurol. (Paris)"},{"key":"53107_CR4","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1007\/s00439-015-1536-7","volume":"134","author":"C Tesson","year":"2015","unstructured":"Tesson, C., Koht, J. & Stevanin, G. Delving into the complexity of hereditary spastic paraplegias: how unexpected phenotypes and inheritance modes are revolutionizing their nosology. Hum. Genet. 134, 511\u2013538. https:\/\/doi.org\/10.1007\/s00439-015-1536-7 (2015).","journal-title":"Hum. Genet."},{"key":"53107_CR5","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.parkreldis.2021.10.006","volume":"92","author":"SL Hsu","year":"2021","unstructured":"Hsu, S. L. et al. Investigating ABCD1 mutations in a Taiwanese cohort with hereditary spastic paraplegia phenotype. Parkinsonism Relat. Disord. 92, 7\u201312. https:\/\/doi.org\/10.1016\/j.parkreldis.2021.10.006 (2021).","journal-title":"Parkinsonism Relat. Disord"},{"key":"53107_CR6","doi-asserted-by":"publisher","first-page":"e1065","DOI":"10.1002\/mgg3.1065","volume":"8","author":"WJ Luo","year":"2020","unstructured":"Luo, W. J. et al. Spastic paraplegia as the predominant phenotype in a cohort of Chinese patients with adrenoleukodystrophy. Mol. Genet. Genomic Med. 8, e1065. https:\/\/doi.org\/10.1002\/mgg3.1065 (2020).","journal-title":"Mol. Genet. Genomic Med."},{"key":"53107_CR7","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.jns.2015.07.024","volume":"357","author":"H Park","year":"2015","unstructured":"Park, H. et al. Mutational spectrum of the SPAST and ATL1 genes in Korean patients with hereditary spastic paraplegia. J. Neurol. Sci. 357, 167\u2013172. https:\/\/doi.org\/10.1016\/j.jns.2015.07.024 (2015).","journal-title":"J. Neurol. Sci."},{"key":"53107_CR8","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1093\/brain\/awab386","volume":"145","author":"JL M\u00e9reaux","year":"2022","unstructured":"M\u00e9reaux, J. L. et al. Clinical and genetic spectra of 1550 index patients with hereditary spastic paraplegia. Brain 145, 1029\u20131037. https:\/\/doi.org\/10.1093\/brain\/awab386 (2022).","journal-title":"Brain"},{"key":"53107_CR9","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.parkreldis.2019.11.007","volume":"69","author":"Z Zhu","year":"2019","unstructured":"Zhu, Z. et al. Novel mutations in the SPAST gene cause hereditary spastic paraplegia. Parkinsonism Relat. Disord. 69, 125\u2013133. https:\/\/doi.org\/10.1016\/j.parkreldis.2019.11.007 (2019).","journal-title":"Parkinsonism Relat. Disord"},{"key":"53107_CR10","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1080\/23808993.2019.1599685","volume":"4","author":"N Martinez-Martin","year":"2019","unstructured":"Martinez-Martin, N. & Magnus, D. Privacy and ethical challenges in next-generation sequencing. Expert Rev. Precis Med. Drug Dev. 4, 95\u2013104. https:\/\/doi.org\/10.1080\/23808993.2019.1599685 (2019).","journal-title":"Expert Rev. Precis Med. Drug Dev."},{"key":"53107_CR11","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1038\/gim.2013.73","volume":"15","author":"RC Green","year":"2013","unstructured":"Green, R. C. et al. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet. Med. 15, 565\u2013574. https:\/\/doi.org\/10.1038\/gim.2013.73 (2013).","journal-title":"Genet. Med."},{"key":"53107_CR12","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1038\/15472","volume":"23","author":"J Hazan","year":"1999","unstructured":"Hazan, J. et al. Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia. Nat. Genet. 23, 296\u2013303. https:\/\/doi.org\/10.1038\/15472 (1999).","journal-title":"Nat. Genet."},{"key":"53107_CR13","doi-asserted-by":"publisher","unstructured":"Liu, Q., Zhang, G., Ji, Z. & Lin, H. Molecular and cellular mechanisms of spastin in neural development and disease (Review). Int. J. Mol. Med. 48 https:\/\/doi.org\/10.3892\/ijmm.2021.5051 (2021).","DOI":"10.3892\/ijmm.2021.5051"},{"key":"53107_CR14","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.jsb.2012.03.002","volume":"179","author":"JL Taylor","year":"2012","unstructured":"Taylor, J. L., White, S. R., Lauring, B. & Kull, F. J. Crystal structure of the human spastin AAA domain. J. Struct. Biol. 179, 133\u2013137. https:\/\/doi.org\/10.1016\/j.jsb.2012.03.002 (2012).","journal-title":"J. Struct. Biol."},{"key":"53107_CR15","doi-asserted-by":"publisher","first-page":"e3","DOI":"10.1093\/brain\/awv247","volume":"139","author":"E Panza","year":"2016","unstructured":"Panza, E. et al. ALDH18A1 gene mutations cause dominant spastic paraplegia SPG9: loss of function effect and plausibility of a dominant negative mechanism. Brain 139, e3. https:\/\/doi.org\/10.1093\/brain\/awv247 (2016).","journal-title":"Brain"},{"key":"53107_CR16","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s13023-019-1008-6","volume":"14","author":"IC Huffnagel","year":"2019","unstructured":"Huffnagel, I. C. et al. Disease progression in women with X-linked adrenoleukodystrophy is slow. Orphanet J. Rare Dis. 14, 30. https:\/\/doi.org\/10.1186\/s13023-019-1008-6 (2019).","journal-title":"Orphanet J. Rare Dis."},{"key":"53107_CR17","doi-asserted-by":"publisher","first-page":"1131888","DOI":"10.3389\/fneur.2023.1131888","volume":"14","author":"MY Chun","year":"2023","unstructured":"Chun, M. Y. et al. Case report: Cerebrotendinous xanthomatosis with a novel mutation in the CYP27A1 gene mimicking behavioral variant frontotemporal dementia. Front. Neurol. 14, 1131888. https:\/\/doi.org\/10.3389\/fneur.2023.1131888 (2023).","journal-title":"Front. Neurol."},{"key":"53107_CR18","doi-asserted-by":"publisher","first-page":"1085228","DOI":"10.3389\/fneur.2023.1085228","volume":"14","author":"A Ikeda","year":"2023","unstructured":"Ikeda, A. et al. Genetic and clinical features of pediatric-onset hereditary spastic paraplegia: a single-center study in Japan. Front. Neurol. 14, 1085228. https:\/\/doi.org\/10.3389\/fneur.2023.1085228 (2023).","journal-title":"Front. Neurol."},{"key":"53107_CR19","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1002\/mds.29728","volume":"39","author":"Y Cao","year":"2024","unstructured":"Cao, Y. et al. Clinical and Genetic Spectrum in a Large Cohort of Hereditary Spastic Paraplegia. Mov. Disord. 39, 651\u2013662. https:\/\/doi.org\/10.1002\/mds.29728 (2024).","journal-title":"Mov. Disord"},{"key":"53107_CR20","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.ejpn.2025.06.001","volume":"57","author":"VL Colona","year":"2025","unstructured":"Colona, V. L. et al. Genotype variability in early-onset Hereditary Spastic Paraplegia: a single-center study. Eur. J. Paediatr. Neurol. 57, 82\u201390. https:\/\/doi.org\/10.1016\/j.ejpn.2025.06.001 (2025).","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"53107_CR21","doi-asserted-by":"publisher","first-page":"1239725","DOI":"10.3389\/fneur.2023.1239725","volume":"14","author":"AC Mahungu","year":"2023","unstructured":"Mahungu, A. C. et al. The mutational profile in a South African cohort with inherited neuropathies and spastic paraplegia. Front. Neurol. 14, 1239725. https:\/\/doi.org\/10.3389\/fneur.2023.1239725 (2023).","journal-title":"Front. Neurol."},{"key":"53107_CR22","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s10048-024-00755-x","volume":"25","author":"M Brankovic","year":"2024","unstructured":"Brankovic, M. et al. Whole exome sequencing in Serbian patients with hereditary spastic paraplegia. Neurogenetics 25, 165\u2013177. https:\/\/doi.org\/10.1007\/s10048-024-00755-x (2024).","journal-title":"Neurogenetics"},{"key":"53107_CR23","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1159\/000531507","volume":"14","author":"A Ghasemi","year":"2023","unstructured":"Ghasemi, A., Sadr, Z., Babanejad, M., Rohani, M. & Alavi, A. Copy number variations in hereditary spastic paraplegia-related genes: Evaluation of an Iranian hereditary spastic paraplegia cohort and literature review. Mol. Syndromol. 14, 477\u2013484. https:\/\/doi.org\/10.1159\/000531507 (2023).","journal-title":"Mol. Syndromol"},{"key":"53107_CR24","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1080\/01677063.2019.1566326","volume":"33","author":"M Almomen","year":"2019","unstructured":"Almomen, M. et al. High diagnostic yield and novel variants in very late-onset spasticity. J. Neurogenet. 33, 27\u201332. https:\/\/doi.org\/10.1080\/01677063.2019.1566326 (2019).","journal-title":"J. Neurogenet."},{"key":"53107_CR25","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/s0140-6736(83)92879-9","volume":"1","author":"AE Harding","year":"1983","unstructured":"Harding, A. E. Classification of the hereditary ataxias and paraplegias. Lancet 1, 1151\u20131155. https:\/\/doi.org\/10.1016\/s0140-6736(83)92879-9 (1983).","journal-title":"Lancet"},{"key":"53107_CR26","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards, S. et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 17, 405\u2013424. https:\/\/doi.org\/10.1038\/gim.2015.30 (2015).","journal-title":"Genet. Med."},{"key":"53107_CR27","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.cell.2018.12.015","volume":"176","author":"K Jaganathan","year":"2019","unstructured":"Jaganathan, K. et al. Predicting splicing from primary sequence with deep learning. Cell 176, 535\u2013548. https:\/\/doi.org\/10.1016\/j.cell.2018.12.015 (2019).","journal-title":"Cell"},{"key":"53107_CR28","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1016\/j.ajhg.2023.06.002","volume":"110","author":"LC Walker","year":"2023","unstructured":"Walker, L. C. et al. ClinGen sequence variant interpretation working group. Using the ACMG\/AMP framework to capture evidence related to predicted and observed impact on splicing: recommendations from the ClinGen SVI splicing subgroup. Am. J. Hum. Genet. 110, 1046\u20131067. https:\/\/doi.org\/10.1016\/j.ajhg.2023.06.002 (2023).","journal-title":"Am. J. Hum. Genet."},{"key":"53107_CR29","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.jmoldx.2024.01.004","volume":"26","author":"JK Lee","year":"2024","unstructured":"Lee, J. K. et al. Enhancing the Reliability of PMP22 Copy Number Variation Detection with an Inherited Peripheral Neuropathy Panel. J. Mol. Diagn. 26, 304\u2013309. https:\/\/doi.org\/10.1016\/j.jmoldx.2024.01.004 (2024).","journal-title":"J. Mol. Diagn."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-53107-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-53107-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-53107-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T12:05:41Z","timestamp":1786449941000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-53107-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,30]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["53107"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-53107-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,30]]},"assertion":[{"value":"13 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the institutional review board of Samsung Medical Center (IRB No.: SMC 2025-06-073) and adhered to the tenets of the Declaration of Helsinki.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"24844"}}