{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T03:27:24Z","timestamp":1786591644357,"version":"build-2736575974"},"reference-count":75,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurol Sci"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Many neurological disorders (NDs) have a genetic basis, yet traditional diagnostic tools such as EEGs, EMGs, and neuroimaging primarily capture downstream manifestations. Although short-read sequencing (SRS) has advanced genetic diagnostics, significant gaps remain. Large repeat expansions, complex structural variants, mitochondrial variants, transcript splicing alterations, and epigenetic changes, all common contributors to NDs, are difficult to resolve with SRS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This review examines the capabilities of long-read sequencing (LRS) technologies in addressing these limitations. We evaluate studies leveraging LRS for genetic diagnosis in NDs and assess current barriers to clinical adoption, including technological, analytical, cost-related, and ethical considerations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>By producing read lengths of tens of kilobases or more, LRS enables detection of variant types often inaccessible to SRS. Recent work has demonstrated its power in conditions such as Duchenne muscular dystrophy, fragile X syndrome, spinocerebellar ataxias, and unresolved mitochondrial syndromes. These findings highlight the potential of LRS to substantially increase diagnostic yield in NDs. However, major challenges persist: the need for high-quality DNA, demanding analytic pipelines, limited access outside major research centers, high costs, and ethical concerns including equity and management of incidental findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>LRS offers advantages for identifying complex genomic contributors to NDs and holds promise for improving diagnostic accuracy. Nonetheless, key technical, logistical, and ethical barriers must be addressed before widespread implementation is feasible. This review outlines current strengths, limitations, and emerging applications of LRS to guide clinicians and researchers in understanding how the technology can be applied today and what is needed for broader adoption.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10072-026-09283-y","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T05:37:59Z","timestamp":1785562679000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-read sequencing for neurological disorders: opportunities, challenges, and future directions"],"prefix":"10.1007","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5836-0916","authenticated-orcid":false,"given":"Hanabi","family":"Geiger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Furuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Lakshitha A.","family":"Perera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory J.","family":"Tinker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"John A.","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"9283_CR1","unstructured":"National Academies of Sciences E, Division H and M, Services B on HC, Techniques C on IN or ID or E (2023) Techniques for Neurological Disorders. Advances in the Diagnosis and Evaluation of Disabling Physical Health Conditions. National Academies Press (US)"},{"key":"9283_CR2","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1111\/ane.12232","volume":"198","author":"M Toft","year":"2014","unstructured":"Toft M (2014) Advances in genetic diagnosis of neurological disorders. Acta Neurol Scand Suppl 198:20\u201325. https:\/\/doi.org\/10.1111\/ane.12232","journal-title":"Acta Neurol Scand Suppl"},{"issue":"11","key":"9283_CR3","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1038\/s41436-021-01242-6","volume":"23","author":"K Manickam","year":"2021","unstructured":"Manickam K, McClain MR, Demmer LA et al (2021) Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med 23(11):2029\u20132037. https:\/\/doi.org\/10.1038\/s41436-021-01242-6","journal-title":"Genet Med"},{"issue":"1","key":"9283_CR4","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/s40478-021-01201-x","volume":"9","author":"SR Chintalaphani","year":"2021","unstructured":"Chintalaphani SR, Pineda SS, Deveson IW, Kumar KR (2021) An update on the neurological short tandem repeat expansion disorders and the emergence of long-read sequencing diagnostics. Acta Neuropathol Commun 9(1):98. https:\/\/doi.org\/10.1186\/s40478-021-01201-x","journal-title":"Acta Neuropathol Commun"},{"issue":"10","key":"9283_CR5","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/s41576-020-0236-x","volume":"21","author":"GA Logsdon","year":"2020","unstructured":"Logsdon GA, Vollger MR, Eichler EE (2020) Long-read human genome sequencing and its applications. Nat Rev Genet 21(10):597\u2013614. https:\/\/doi.org\/10.1038\/s41576-020-0236-x","journal-title":"Nat Rev Genet"},{"issue":"6","key":"9283_CR6","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1093\/dnares\/dsw038","volume":"23","author":"B Arbeithuber","year":"2016","unstructured":"Arbeithuber B, Makova KD, Tiemann-Boege I (2016) Artifactual mutations resulting from DNA lesions limit detection levels in ultrasensitive sequencing applications. DNA Res 23(6):547\u2013559. https:\/\/doi.org\/10.1093\/dnares\/dsw038","journal-title":"DNA Res"},{"key":"9283_CR7","doi-asserted-by":"publisher","unstructured":"Wang B, Jia P, Gao S et al (2025) Long and accurate: how HiFi sequencing is transforming genomics. Genomics Proteomics Bioinformatics 23(1):qzaf003. https:\/\/doi.org\/10.1093\/gpbjnl\/qzaf003","DOI":"10.1093\/gpbjnl\/qzaf003"},{"key":"9283_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/nature.2012.10051","author":"E Check Hayden","year":"2012","unstructured":"Check Hayden E (2012) Nanopore genome sequencer makes its debut. Nature. https:\/\/doi.org\/10.1038\/nature.2012.10051","journal-title":"Nature"},{"issue":"5","key":"9283_CR9","doi-asserted-by":"publisher","first-page":"1786","DOI":"10.1111\/1755-0998.13588","volume":"22","author":"F Trigodet","year":"2022","unstructured":"Trigodet F, Lolans K, Fogarty E et al (2022) High molecular weight DNA extraction strategies for long\u2010read sequencing of complex metagenomes. Mol Ecol Resour 22(5):1786\u20131802. https:\/\/doi.org\/10.1111\/1755-0998.13588","journal-title":"Mol Ecol Resour"},{"issue":"1","key":"9283_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20340-8","volume":"12","author":"K Sahlin","year":"2021","unstructured":"Sahlin K, Medvedev P (2021) Error correction enables use of Oxford Nanopore technology for reference-free transcriptome analysis. Nat Commun 12(1):2. https:\/\/doi.org\/10.1038\/s41467-020-20340-8","journal-title":"Nat Commun"},{"key":"9283_CR11","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/B978-0-444-63233-3.00009-9","volume":"147","author":"H Paulson","year":"2018","unstructured":"Paulson H (2018) Repeat expansion diseases. Handb Clin Neurol 147:105\u2013123. https:\/\/doi.org\/10.1016\/B978-0-444-63233-3.00009-9","journal-title":"Handb Clin Neurol"},{"issue":"1","key":"9283_CR12","doi-asserted-by":"publisher","DOI":"10.1038\/s41525-022-00331-y","volume":"7","author":"S Miyatake","year":"2022","unstructured":"Miyatake S, Koshimizu E, Fujita A et al (2022) Rapid and comprehensive diagnostic method for repeat expansion diseases using nanopore sequencing. NPJ Genom Med 7(1):62. https:\/\/doi.org\/10.1038\/s41525-022-00331-y","journal-title":"NPJ Genom Med"},{"key":"9283_CR13","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/978-1-0716-2996-3_11","volume":"2632","author":"S Mitsuhashi","year":"2023","unstructured":"Mitsuhashi S, Frith MC (2023) Analysis of tandem repeat expansions using long DNA reads. Methods Mol Biol 2632:147\u2013159. https:\/\/doi.org\/10.1007\/978-1-0716-2996-3_11","journal-title":"Methods Mol Biol"},{"issue":"6","key":"9283_CR14","doi-asserted-by":"publisher","first-page":"2725","DOI":"10.3390\/ijms26062725","volume":"26","author":"L Kaplun","year":"2025","unstructured":"Kaplun L, Krautz-Peterson G, Neerman N et al (2025) ONT in clinical diagnostics of repeat expansion disorders: detection and reporting challenges. Int J Mol Sci 26(6):2725. https:\/\/doi.org\/10.3390\/ijms26062725","journal-title":"Int J Mol Sci"},{"issue":"1","key":"9283_CR15","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s13024-018-0274-4","volume":"13","author":"MTW Ebbert","year":"2018","unstructured":"Ebbert MTW, Farrugia SL, Sens JP et al (2018) Long-read sequencing across the C9orf72 \u201cGGGGCC\u201d repeat expansion: implications for clinical use and genetic discovery efforts in human disease. Mol Neurodegener 13(1):46. https:\/\/doi.org\/10.1186\/s13024-018-0274-4","journal-title":"Mol Neurodegener"},{"key":"9283_CR16","doi-asserted-by":"publisher","first-page":"1611676","DOI":"10.3389\/pore.2024.1611676","volume":"30","author":"N Szak\u00e1llas","year":"2024","unstructured":"Szak\u00e1llas N, Bart\u00e1k BK, Valcz G, Nagy ZB, Tak\u00e1cs I, Moln\u00e1r B (2024) Can long-read sequencing tackle the barriers, which the next-generation could not? A review Pathol Oncol Res 30:1611676. https:\/\/doi.org\/10.3389\/pore.2024.1611676","journal-title":"A review Pathol Oncol Res"},{"key":"9283_CR17","doi-asserted-by":"publisher","first-page":"1114542","DOI":"10.3389\/fgene.2022.1114542","volume":"13","author":"I Wohlers","year":"2023","unstructured":"Wohlers I, Garg S, Hehir-Kwa JY (2023) Editorial: Long-read sequencing\u2014Pitfalls, benefits and success stories. Front Genet 13:1114542. https:\/\/doi.org\/10.3389\/fgene.2022.1114542","journal-title":"Front Genet"},{"issue":"4","key":"9283_CR18","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1534\/g3.119.400864","volume":"10","author":"Y Fukasawa","year":"2020","unstructured":"Fukasawa Y, Ermini L, Wang H, Carty K, Cheung MS (2020) LongQC: a quality control tool for third generation sequencing long read data. G3 (Bethesda) 10(4):1193\u20131196. https:\/\/doi.org\/10.1534\/g3.119.400864","journal-title":"G3 (Bethesda)"},{"issue":"7809","key":"9283_CR19","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1038\/s41586-020-2287-8","volume":"581","author":"RL Collins","year":"2020","unstructured":"Collins RL, Brand H, Karczewski KJ et al (2020) A structural variation reference for medical and population genetics. Nature 581(7809):444\u2013451. https:\/\/doi.org\/10.1038\/s41586-020-2287-8","journal-title":"Nature"},{"issue":"9","key":"9283_CR20","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25094801","volume":"25","author":"A Miano-Burkhardt","year":"2024","unstructured":"Miano-Burkhardt A, Alvarez Jerez P, Daida K, Bandres Ciga S, Billingsley KJ (2024) The role of structural variants in the genetic architecture of Parkinson\u2019s disease. Int J Mol Sci 25(9):4801. https:\/\/doi.org\/10.3390\/ijms25094801","journal-title":"Int J Mol Sci"},{"issue":"2","key":"9283_CR21","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.neuron.2011.09.011","volume":"72","author":"M DeJesus-Hernandez","year":"2011","unstructured":"DeJesus-Hernandez M, Mackenzie IR, Boeve BF et al (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72(2):245\u2013256. https:\/\/doi.org\/10.1016\/j.neuron.2011.09.011","journal-title":"Neuron"},{"issue":"5","key":"9283_CR22","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1038\/s41588-018-0107-y","volume":"50","author":"DM Werling","year":"2018","unstructured":"Werling DM, Brand H, An JY et al (2018) An analytical framework for whole-genome sequence association studies and its implications for autism spectrum disorder. Nat Genet 50(5):727\u2013736. https:\/\/doi.org\/10.1038\/s41588-018-0107-y","journal-title":"Nat Genet"},{"issue":"3","key":"9283_CR23","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.ajhg.2013.01.011","volume":"92","author":"J Beck","year":"2013","unstructured":"Beck J, Poulter M, Hensman D et al (2013) Large C9orf72 hexanucleotide repeat expansions are seen in multiple neurodegenerative syndromes and are more frequent than expected in the UK population. Am J Hum Genet 92(3):345\u2013353. https:\/\/doi.org\/10.1016\/j.ajhg.2013.01.011","journal-title":"Am J Hum Genet"},{"key":"9283_CR24","doi-asserted-by":"publisher","first-page":"1374860","DOI":"10.3389\/fgene.2024.1374860","volume":"15","author":"G Olivucci","year":"2024","unstructured":"Olivucci G, Iovino E, Innella G, Turchetti D, Pippucci T, Magini P (2024) Long read sequencing on its way to the routine diagnostics of genetic diseases. Front Genet 15:1374860. https:\/\/doi.org\/10.3389\/fgene.2024.1374860","journal-title":"Front Genet"},{"issue":"11","key":"9283_CR25","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1002\/humu.24465","volume":"43","author":"LK Conlin","year":"2022","unstructured":"Conlin LK, Aref-Eshghi E, McEldrew DA, Luo M, Rajagopalan R (2022) Long-read sequencing for molecular diagnostics in constitutional genetic disorders. Hum Mutat 43(11):1531\u20131544. https:\/\/doi.org\/10.1002\/humu.24465","journal-title":"Hum Mutat"},{"key":"9283_CR26","doi-asserted-by":"publisher","DOI":"10.1101\/2024.04.18.590093","author":"S Schloissnig","year":"2024","unstructured":"Schloissnig S, Pani S, Rodriguez-Martin B et al (2024) Long-read sequencing and structural variant characterization in 1,019 samples from the 1000 Genomes Project. bioRxiv. https:\/\/doi.org\/10.1101\/2024.04.18.590093","journal-title":"bioRxiv"},{"issue":"8","key":"9283_CR27","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1002\/acn3.51612","volume":"9","author":"CC Bruels","year":"2022","unstructured":"Bruels CC, Littel HR, Daugherty AL et al (2022) Diagnostic capabilities of nanopore long-read sequencing in muscular dystrophy. Ann Clin Transl Neurol 9(8):1302\u20131309. https:\/\/doi.org\/10.1002\/acn3.51612","journal-title":"Ann Clin Transl Neurol"},{"issue":"4","key":"9283_CR28","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1619","volume":"9","author":"RJ Butterfield","year":"2021","unstructured":"Butterfield RJ, Imburgia C, Mayne K et al (2021) High throughput screening for expanded CTG repeats in myotonic dystrophy type 1 using melt curve analysis. Mol Genet Genomic Med 9(4):e1619. https:\/\/doi.org\/10.1002\/mgg3.1619","journal-title":"Mol Genet Genomic Med"},{"issue":"3","key":"9283_CR29","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/pd.6334","volume":"43","author":"T Mariya","year":"2023","unstructured":"Mariya T, Shichiri Y, Sugimoto T et al (2023) Clinical application of long-read nanopore sequencing in a preimplantation genetic testing pre-clinical workup to identify the junction for complex Xq chromosome rearrangement-related disease. Prenat Diagn 43(3):304\u2013313. https:\/\/doi.org\/10.1002\/pd.6334","journal-title":"Prenat Diagn"},{"issue":"8","key":"9283_CR30","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202302025","volume":"6","author":"S Ohori","year":"2023","unstructured":"Ohori S, Miyauchi A, Osaka H et al (2023) Biallelic structural variations within FGF12 detected by long-read sequencing in epilepsy. Life Sci Alliance 6(8):e202302025. https:\/\/doi.org\/10.26508\/lsa.202302025","journal-title":"Life Sci Alliance"},{"issue":"1","key":"9283_CR31","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-023-00490-8","volume":"17","author":"A Dami\u00e1n","year":"2023","unstructured":"Dami\u00e1n A, N\u00fa\u00f1ez-Moreno G, Jubin C et al (2023) Long-read genome sequencing identifies cryptic structural variants in congenital aniridia cases. Hum Genomics 17(1):45. https:\/\/doi.org\/10.1186\/s40246-023-00490-8","journal-title":"Hum Genomics"},{"key":"9283_CR32","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-021-04422-y","volume":"22","author":"T Jiang","year":"2021","unstructured":"Jiang T, Liu S, Cao S et al (2021) Long-read sequencing settings for efficient structural variation detection based on comprehensive evaluation. BMC Bioinformatics 22:552. https:\/\/doi.org\/10.1186\/s12859-021-04422-y","journal-title":"BMC Bioinformatics"},{"key":"9283_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41439-024-00276-x","volume":"11","author":"S Kosugi","year":"2024","unstructured":"Kosugi S, Terao C (2024) Comparative evaluation of SNVs, indels, and structural variations detected with short- and long-read sequencing data. Hum Genome Var 11:18. https:\/\/doi.org\/10.1038\/s41439-024-00276-x","journal-title":"Hum Genome Var"},{"issue":"10","key":"9283_CR34","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1038\/s41587-019-0217-9","volume":"37","author":"AM Wenger","year":"2019","unstructured":"Wenger AM, Peluso P, Rowell WJ et al (2019) Accurate circular consensus long-read sequencing improves variant detection and assembly of a human genome. Nat Biotechnol 37(10):1155\u20131162. https:\/\/doi.org\/10.1038\/s41587-019-0217-9","journal-title":"Nat Biotechnol"},{"issue":"2","key":"9283_CR35","doi-asserted-by":"publisher","first-page":"23671","DOI":"10.17161\/sjm.v2i2.23671","volume":"2","author":"X Chen","year":"2025","unstructured":"Chen X, Lu X, Shi X, Yu S, Zhao J (2025) Long-read sequencing outperforms short-read sequencing in detecting most structural variations. Serican J Med 2(2):23671. https:\/\/doi.org\/10.17161\/sjm.v2i2.23671","journal-title":"Serican J Med"},{"key":"9283_CR36","unstructured":"Diagnostic capabilities of nanopore long-read sequencing in muscular dystrophy - PubMed. https:\/\/pubmed.ncbi.nlm.nih.gov\/35734998\/. Accessed 26 Sep 2025"},{"issue":"1","key":"9283_CR37","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/s41398-020-01060-5","volume":"10","author":"J Linthorst","year":"2020","unstructured":"Linthorst J, Meert W, Hestand MS et al (2020) Extreme enrichment of VNTR-associated polymorphicity in human subtelomeres: genes with most VNTRs are predominantly expressed in the brain. Transl Psychiatry 10(1):369. https:\/\/doi.org\/10.1038\/s41398-020-01060-5","journal-title":"Transl Psychiatry"},{"issue":"7624","key":"9283_CR38","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1038\/nature20098","volume":"538","author":"JS Seo","year":"2016","unstructured":"Seo JS, Rhie A, Kim J et al (2016) De novo assembly and phasing of a Korean human genome. Nature 538(7624):243\u2013247. https:\/\/doi.org\/10.1038\/nature20098","journal-title":"Nature"},{"issue":"1","key":"9283_CR39","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1093\/bmb\/ldt017","volume":"106","author":"PF Chinnery","year":"2013","unstructured":"Chinnery PF, Hudson G (2013) Mitochondrial genetics. Br Med Bull 106(1):135\u2013159. https:\/\/doi.org\/10.1093\/bmb\/ldt017","journal-title":"Br Med Bull"},{"issue":"2","key":"9283_CR40","doi-asserted-by":"publisher","first-page":"143","DOI":"10.2174\/1570159x13666150703154541","volume":"14","author":"S Arun","year":"2016","unstructured":"Arun S, Liu L, Donmez G (2016) Mitochondrial biology and neurological diseases. Curr Neuropharmacol 14(2):143\u2013154. https:\/\/doi.org\/10.2174\/1570159x13666150703154541","journal-title":"Curr Neuropharmacol"},{"key":"9283_CR41","doi-asserted-by":"publisher","first-page":"1089956","DOI":"10.3389\/fgene.2023.1089956","volume":"14","author":"C Frascarelli","year":"2023","unstructured":"Frascarelli C, Zanetti N, Nasca A et al (2023) Nanopore long-read next-generation sequencing for detection of mitochondrial DNA large-scale deletions. Front Genet 14:1089956. https:\/\/doi.org\/10.3389\/fgene.2023.1089956","journal-title":"Front Genet"},{"issue":"9","key":"9283_CR42","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1080\/14737159.2023.2241365","volume":"23","author":"WL Macken","year":"2023","unstructured":"Macken WL, Falabella M, Pizzamiglio C et al (2023) Enhanced mitochondrial genome analysis: bioinformatic and long-read sequencing advances and their diagnostic implications. Expert Rev Mol Diagn 23(9):797\u2013814. https:\/\/doi.org\/10.1080\/14737159.2023.2241365","journal-title":"Expert Rev Mol Diagn"},{"key":"9283_CR43","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.mito.2022.06.003","volume":"65","author":"AR Vandiver","year":"2022","unstructured":"Vandiver AR, Pielstick B, Gilpatrick T et al (2022) Long read mitochondrial genome sequencing using Cas9-guided adaptor ligation. Mitochondrion 65:176\u2013183. https:\/\/doi.org\/10.1016\/j.mito.2022.06.003","journal-title":"Mitochondrion"},{"issue":"Suppl 6","key":"9283_CR44","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1186\/s12864-020-07227-0","volume":"21","author":"H Zhang","year":"2020","unstructured":"Zhang H, Jain C, Aluru S (2020) A comprehensive evaluation of long read error correction methods. BMC Genomics 21(Suppl 6):889. https:\/\/doi.org\/10.1186\/s12864-020-07227-0","journal-title":"BMC Genomics"},{"issue":"11","key":"9283_CR45","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24119206","volume":"24","author":"CG Ciobanu","year":"2023","unstructured":"Ciobanu CG, Nuc\u0103 I, Popescu R et al (2023) Narrative review: update on the molecular diagnosis of fragile X syndrome. Int J Mol Sci 24(11):9206. https:\/\/doi.org\/10.3390\/ijms24119206","journal-title":"Int J Mol Sci"},{"issue":"8","key":"9283_CR46","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz107","volume":"47","author":"S Gigante","year":"2019","unstructured":"Gigante S, Gouil Q, Lucattini A et al (2019) Using long-read sequencing to detect imprinted DNA methylation. Nucleic Acids Res 47(8):e46. https:\/\/doi.org\/10.1093\/nar\/gkz107","journal-title":"Nucleic Acids Res"},{"issue":"11","key":"9283_CR47","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26114969","volume":"26","author":"J Park","year":"2025","unstructured":"Park J, Dufke C, Fleszar Z et al (2025) Long-read sequencing identifies mosaic sequence variations in Friedreich\u2019s ataxia-GAA repeats. Int J Mol Sci 26(11):4969. https:\/\/doi.org\/10.3390\/ijms26114969","journal-title":"Int J Mol Sci"},{"issue":"23","key":"9283_CR48","doi-asserted-by":"publisher","first-page":"3818","DOI":"10.1093\/hmg\/ddaa267","volume":"29","author":"LN Rodden","year":"2021","unstructured":"Rodden LN, Chutake YK, Gilliam K et al (2021) Methylated and unmethylated epialleles support variegated epigenetic silencing in Friedreich ataxia. Hum Mol Genet 29(23):3818\u20133829. https:\/\/doi.org\/10.1093\/hmg\/ddaa267","journal-title":"Hum Mol Genet"},{"issue":"8","key":"9283_CR49","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1136\/jmg-2022-108742","volume":"60","author":"C Lam","year":"2023","unstructured":"Lam C, Gilliam KM, Rodden LN, Schadt KA, Lynch DR, Bidichandani S (2023) FXN gene methylation determines carrier status in Friedreich ataxia. J Med Genet 60(8):797\u2013800. https:\/\/doi.org\/10.1136\/jmg-2022-108742","journal-title":"J Med Genet"},{"issue":"6","key":"9283_CR50","doi-asserted-by":"publisher","DOI":"10.3390\/genes13060970","volume":"13","author":"A Rasmussen","year":"2022","unstructured":"Rasmussen A, Hildonen M, Vissing J, Duno M, T\u00fcmer Z, Birkedal U (2022) High resolution analysis of DMPK hypermethylation and repeat interruptions in myotonic dystrophy type 1. Genes (Basel) 13(6):970. https:\/\/doi.org\/10.3390\/genes13060970","journal-title":"Genes (Basel)"},{"issue":"1","key":"9283_CR51","doi-asserted-by":"publisher","first-page":"2449","DOI":"10.1038\/s41467-019-10168-2","volume":"10","author":"Q Liu","year":"2019","unstructured":"Liu Q, Fang L, Yu G, Wang D, Xiao CL, Wang K (2019) Detection of DNA base modifications by deep recurrent neural network on Oxford Nanopore sequencing data. Nat Commun 10(1):2449. https:\/\/doi.org\/10.1038\/s41467-019-10168-2","journal-title":"Nat Commun"},{"key":"9283_CR52","doi-asserted-by":"publisher","unstructured":"Kong Y, Zhang Y, Mead EA et al (2024) Critical assessment of nanopore sequencing for the detection of multiple forms of DNA modifications. bioRxiv. Published online November 19, 2024:2024.11.19.624260. https:\/\/doi.org\/10.1101\/2024.11.19.624260","DOI":"10.1101\/2024.11.19.624260"},{"issue":"5","key":"9283_CR53","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1038\/s41431-022-01190-y","volume":"31","author":"C Geng","year":"2023","unstructured":"Geng C, Zhang C, Li P et al (2023) Identification and characterization of two DMD pedigrees with large inversion mutations based on a long-read sequencing pipeline. Eur J Hum Genet 31(5):504\u2013511. https:\/\/doi.org\/10.1038\/s41431-022-01190-y","journal-title":"Eur J Hum Genet"},{"issue":"5","key":"9283_CR54","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1016\/j.nmd.2023.03.001","volume":"33","author":"J Bai","year":"2023","unstructured":"Bai J, Qu Y, OuYang S et al (2023) Novel Alu-mediated deletions of the SMN1 gene were identified by ultra-long read sequencing technology in patients with spinal muscular atrophy. Neuromuscul Disord 33(5):382\u2013390. https:\/\/doi.org\/10.1016\/j.nmd.2023.03.001","journal-title":"Neuromuscul Disord"},{"issue":"8","key":"9283_CR55","doi-asserted-by":"publisher","first-page":"2541","DOI":"10.1002\/ajmg.a.62349","volume":"185","author":"HL Chin","year":"2021","unstructured":"Chin HL, O\u2019Neill K, Louie K et al (2021) An approach to rapid characterization of DMD copy number variants for prenatal risk assessment. Am J Med Genet A 185(8):2541\u20132545. https:\/\/doi.org\/10.1002\/ajmg.a.62349","journal-title":"Am J Med Genet A"},{"issue":"4","key":"9283_CR56","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1002\/acn3.70008","volume":"12","author":"LI Rudaks","year":"2025","unstructured":"Rudaks LI, Stevanovski I, Yeow D et al (2025) Targeted long-read sequencing as a single assay improves the diagnosis of spastic-ataxia disorders. Ann Clin Transl Neurol 12(4):832\u2013841. https:\/\/doi.org\/10.1002\/acn3.70008","journal-title":"Ann Clin Transl Neurol"},{"issue":"8","key":"9283_CR57","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1038\/s41588-019-0458-z","volume":"51","author":"H Ishiura","year":"2019","unstructured":"Ishiura H, Shibata S, Yoshimura J et al (2019) Noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and an overlapping disease. Nat Genet 51(8):1222\u20131232. https:\/\/doi.org\/10.1038\/s41588-019-0458-z","journal-title":"Nat Genet"},{"issue":"6","key":"9283_CR58","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1093\/brain\/awab077","volume":"144","author":"J Yu","year":"2021","unstructured":"Yu J, Deng J, Guo X et al (2021) The GGC repeat expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy type 3. Brain 144(6):1819\u20131832. https:\/\/doi.org\/10.1093\/brain\/awab077","journal-title":"Brain"},{"issue":"1","key":"9283_CR59","doi-asserted-by":"publisher","first-page":"6327","DOI":"10.1038\/s41467-024-49950-2","volume":"15","author":"A Cortese","year":"2024","unstructured":"Cortese A, Beecroft SJ, Facchini S et al (2024) A CCG expansion in ABCD3 causes oculopharyngodistal myopathy in individuals of European ancestry. Nat Commun 15(1):6327. https:\/\/doi.org\/10.1038\/s41467-024-49950-2","journal-title":"Nat Commun"},{"issue":"7","key":"9283_CR60","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/j.nmd.2023.05.004","volume":"33","author":"P Yeetong","year":"2023","unstructured":"Yeetong P, Kulsirichawaroj P, Kumutpongpanich T et al (2023) Long-read Nanopore sequencing identified D4Z4 contractions in patients with facioscapulohumeral muscular dystrophy. Neuromuscul Disord 33(7):551\u2013556. https:\/\/doi.org\/10.1016\/j.nmd.2023.05.004","journal-title":"Neuromuscul Disord"},{"issue":"5","key":"9283_CR61","doi-asserted-by":"publisher","first-page":"2616","DOI":"10.3390\/ijms22052616","volume":"22","author":"A Mangin","year":"2021","unstructured":"Mangin A, de Pontual L, Tsai YC et al (2021) Robust detection of somatic mosaicism and repeat interruptions by long-read targeted sequencing in myotonic dystrophy type 1. Int J Mol Sci 22(5):2616. https:\/\/doi.org\/10.3390\/ijms22052616","journal-title":"Int J Mol Sci"},{"issue":"7","key":"9283_CR62","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1016\/j.jmoldx.2022.04.006","volume":"24","author":"A Perrin","year":"2022","unstructured":"Perrin A, Van Goethem C, Th\u00e8ze C et al (2022) Long-reads sequencing strategy to localize variants in TTN repeated domains. J Mol Diagn 24(7):719\u2013726. https:\/\/doi.org\/10.1016\/j.jmoldx.2022.04.006","journal-title":"J Mol Diagn"},{"issue":"1","key":"9283_CR63","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s13073-023-01183-6","volume":"15","author":"E Kucuk","year":"2023","unstructured":"Kucuk E, van der Sanden BPGH, O\u2019Gorman L et al (2023) Comprehensive de novo mutation discovery with HiFi long-read sequencing. Genome Med 15(1):34. https:\/\/doi.org\/10.1186\/s13073-023-01183-6","journal-title":"Genome Med"},{"issue":"11","key":"9283_CR64","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1093\/clinchem\/hvad152","volume":"69","author":"S Li","year":"2023","unstructured":"Li S, Han X, Zhang L et al (2023) An effective and universal long-read sequencing-based approach for SMN1 2 + 0 carrier screening through family trio analysis. Clin Chem 69(11):1295\u20131306. https:\/\/doi.org\/10.1093\/clinchem\/hvad152","journal-title":"Clin Chem"},{"issue":"8","key":"9283_CR65","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1038\/s41588-019-0459-y","volume":"51","author":"J Sone","year":"2019","unstructured":"Sone J, Mitsuhashi S, Fujita A et al (2019) Long-read sequencing identifies GGC repeat expansions in NOTCH2NLC associated with neuronal intranuclear inclusion disease. Nat Genet 51(8):1215\u20131221. https:\/\/doi.org\/10.1038\/s41588-019-0459-y","journal-title":"Nat Genet"},{"issue":"4","key":"9283_CR66","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/s41588-018-0067-2","volume":"50","author":"H Ishiura","year":"2018","unstructured":"Ishiura H, Doi K, Mitsui J et al (2018) Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy. Nat Genet 50(4):581\u2013590. https:\/\/doi.org\/10.1038\/s41588-018-0067-2","journal-title":"Nat Genet"},{"issue":"2","key":"9283_CR67","doi-asserted-by":"publisher","DOI":"10.1016\/j.xhgg.2021.100023","volume":"2","author":"SM Hiatt","year":"2021","unstructured":"Hiatt SM, Lawlor JMJ, Handley LH et al (2021) Long-read genome sequencing for the molecular diagnosis of neurodevelopmental disorders. Hum Genet Genomics Adv 2(2):100023. https:\/\/doi.org\/10.1016\/j.xhgg.2021.100023","journal-title":"Hum Genet Genomics Adv"},{"issue":"1","key":"9283_CR68","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-021-02443-7","volume":"22","author":"M Alser","year":"2021","unstructured":"Alser M, Rotman J, Deshpande D et al (2021) Technology dictates algorithms: recent developments in read alignment. Genome Biol 22(1):249. https:\/\/doi.org\/10.1186\/s13059-021-02443-7","journal-title":"Genome Biol"},{"key":"9283_CR69","doi-asserted-by":"publisher","DOI":"10.3389\/pore.2024.1611676","volume":"30","author":"N Szak\u00e1llas","year":"2024","unstructured":"Szak\u00e1llas N, Bart\u00e1k BK, Valcz G, Nagy ZB, Tak\u00e1cs I, Moln\u00e1r B (2024) Can long-read sequencing tackle the barriers, which the next-generation could not? A review. Pathol Oncol Res 30:1611676. https:\/\/doi.org\/10.3389\/pore.2024.1611676","journal-title":"Pathol Oncol Res"},{"issue":"3","key":"9283_CR70","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2024.110842","volume":"116","author":"E Espinosa","year":"2024","unstructured":"Espinosa E, Bautista R, Larrosa R, Plata O (2024) Advancements in long-read genome sequencing technologies and algorithms. Genomics 116(3):110842. https:\/\/doi.org\/10.1016\/j.ygeno.2024.110842","journal-title":"Genomics"},{"issue":"1","key":"9283_CR71","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s40246-023-00522-3","volume":"17","author":"JB Oehler","year":"2023","unstructured":"Oehler JB, Wright H, Stark Z, Mallett AJ, Schmitz U (2023) The application of long-read sequencing in clinical settings. Hum Genomics 17(1):73. https:\/\/doi.org\/10.1186\/s40246-023-00522-3","journal-title":"Hum Genomics"},{"issue":"5","key":"9283_CR72","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1007\/s00401-017-1743-5","volume":"134","author":"P Euskirchen","year":"2017","unstructured":"Euskirchen P, Bielle F, Labreche K et al (2017) Same-day genomic and epigenomic diagnosis of brain tumors using real-time nanopore sequencing. Acta Neuropathol 134(5):691\u2013703. https:\/\/doi.org\/10.1007\/s00401-017-1743-5","journal-title":"Acta Neuropathol"},{"issue":"1","key":"9283_CR73","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-022-01026-w","volume":"14","author":"S Marwaha","year":"2022","unstructured":"Marwaha S, Knowles JW, Ashley EA (2022) A guide for the diagnosis of rare and undiagnosed disease: beyond the exome. Genome Med 14(1):23. https:\/\/doi.org\/10.1186\/s13073-022-01026-w","journal-title":"Genome Med"},{"issue":"1","key":"9283_CR74","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e23914","volume":"10","author":"D Horgan","year":"2024","unstructured":"Horgan D, Van den Bulcke M, Malapelle U et al (2024) Tackling the implementation gap for the uptake of NGS and advanced molecular diagnostics into healthcare systems. Heliyon 10(1):e23914. https:\/\/doi.org\/10.1016\/j.heliyon.2023.e23914","journal-title":"Heliyon"},{"issue":"11","key":"9283_CR75","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1101\/gr.279168.124","volume":"34","author":"SV Iyer","year":"2024","unstructured":"Iyer SV, Goodwin S, McCombie WR (2024) Leveraging the power of long reads for targeted sequencing. Genome Res 34(11):1701\u20131718. https:\/\/doi.org\/10.1101\/gr.279168.124","journal-title":"Genome Res"}],"container-title":["Neurological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10072-026-09283-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10072-026-09283-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10072-026-09283-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T02:41:15Z","timestamp":1786588875000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10072-026-09283-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":75,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["9283"],"URL":"https:\/\/doi.org\/10.1007\/s10072-026-09283-y","relation":{},"ISSN":["1590-1874","1590-3478"],"issn-type":[{"value":"1590-1874","type":"print"},{"value":"1590-3478","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"9 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"None.","order":1,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"None.","order":2,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"675"}}