{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:18:03Z","timestamp":1790788683018,"version":"4.1.0"},"reference-count":19,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T00:00:00Z","timestamp":1697673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/T001712\/1"],"award-info":[{"award-number":["MR\/T001712\/1"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["2019-1836"],"award-info":[{"award-number":["2019-1836"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["20229MMHXP"],"award-info":[{"award-number":["20229MMHXP"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002803","name":"Fondazione Cariplo","doi-asserted-by":"publisher","award":["MR\/T001712\/1"],"award-info":[{"award-number":["MR\/T001712\/1"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002803","name":"Fondazione Cariplo","doi-asserted-by":"publisher","award":["2019-1836"],"award-info":[{"award-number":["2019-1836"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002803","name":"Fondazione Cariplo","doi-asserted-by":"publisher","award":["20229MMHXP"],"award-info":[{"award-number":["20229MMHXP"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Inherited Neuropathy Consortium, National Ministry of Health","award":["MR\/T001712\/1"],"award-info":[{"award-number":["MR\/T001712\/1"]}]},{"name":"Inherited Neuropathy Consortium, National Ministry of Health","award":["2019-1836"],"award-info":[{"award-number":["2019-1836"]}]},{"name":"Inherited Neuropathy Consortium, National Ministry of Health","award":["20229MMHXP"],"award-info":[{"award-number":["20229MMHXP"]}]},{"name":"Italian Ministry for Universities and Research","award":["MR\/T001712\/1"],"award-info":[{"award-number":["MR\/T001712\/1"]}]},{"name":"Italian Ministry for Universities and Research","award":["2019-1836"],"award-info":[{"award-number":["2019-1836"]}]},{"name":"Italian Ministry for Universities and Research","award":["20229MMHXP"],"award-info":[{"award-number":["20229MMHXP"]}]},{"name":"National Brain Appeal\u2019s Innovation Fund and Rosetrees Trust","award":["MR\/T001712\/1"],"award-info":[{"award-number":["MR\/T001712\/1"]}]},{"name":"National Brain Appeal\u2019s Innovation Fund and Rosetrees Trust","award":["2019-1836"],"award-info":[{"award-number":["2019-1836"]}]},{"name":"National Brain Appeal\u2019s Innovation Fund and Rosetrees Trust","award":["20229MMHXP"],"award-info":[{"award-number":["20229MMHXP"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>A recessive Short Tandem Repeat expansion in RFC1 has been found to be associated with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), and to be a frequent cause of late onset ataxia and sensory neuropathy. The usual procedure for sizing these expansions is based on Southern Blotting (SB), a time-consuming and a relatively imprecise technique. In this paper, we compare SB with Optical Genome Mapping (OGM), a method for detecting Structural Variants (SVs) based on the measurement of distances between fluorescently labelled probes, for the diagnosis of RFC1 CANVAS and disease spectrum. The two methods are applied to 17 CANVAS patients\u2019 blood samples and resulting sizes compared, showing a good agreement. Further, long-read sequencing is used for two patients to investigate the agreement of sizes with either SB or OGM. Our study concludes that OGM represents a viable alternative to SB, allowing for a simpler technique, a more precise sizing of the expansion and ability to expand analysis of SV in the entire genome as opposed to SB which is a locus specific method.<\/jats:p>","DOI":"10.3390\/biom13101546","type":"journal-article","created":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T05:43:28Z","timestamp":1697694208000},"page":"1546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Optical Genome Mapping Enables Detection and Accurate Sizing of RFC1 Repeat Expansions"],"prefix":"10.3390","volume":"13","author":[{"given":"Stefano","family":"Facchini","sequence":"first","affiliation":[{"name":"IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Department of Neuromuscular Diseases, University College London, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Dominik","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, University College London, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Manini","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, University College London, London WC1N 3BG, UK"},{"name":"Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"},{"name":"Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, 20149 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Efthymiou","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, University College London, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Curr\u00f2","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, University College London, London WC1N 3BG, UK"},{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Rugginini","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, University College London, London WC1N 3BG, UK"},{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Vegezzi","sequence":"additional","affiliation":[{"name":"IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Quartesan","sequence":"additional","affiliation":[{"name":"IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Perrone","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, University College London, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahedah Koya","family":"Kutty","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kulliyah of Medicine, International Islamic University Malaysia (IIUM), Pahang 53100, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7123-8011","authenticated-orcid":false,"given":"Valentina","family":"Galassi Deforie","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, University College London, London WC1N 3BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo P.","family":"Schnekenberg","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, University College London, London WC1N 3BG, UK"},{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0797-8282","authenticated-orcid":false,"given":"Elena","family":"Abati","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, University College London, London WC1N 3BG, UK"},{"name":"Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5654-4088","authenticated-orcid":false,"given":"Anna","family":"Pichiecchio","sequence":"additional","affiliation":[{"name":"IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0600-6820","authenticated-orcid":false,"given":"Enza Maria","family":"Valente","sequence":"additional","affiliation":[{"name":"IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1513-2113","authenticated-orcid":false,"given":"Cristina","family":"Tassorelli","sequence":"additional","affiliation":[{"name":"IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"Reilly","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/s41588-019-0372-4","article-title":"Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia","volume":"51","author":"Cortese","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ajhg.2019.05.016","article-title":"Bioinformatics-Based Identification of Expanded Repeats: A Non-reference Intronic Pentamer Expansion in RFC1 Causes CANVAS","volume":"105","author":"Rafehi","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Dominik, N., Magri, S., Curr\u00f2, R., Abati, E., Facchini, S., Corbetta, M., Hannah, M., Daniela, D.B., Elisa, S., and Igor, S. (2023). Normal and pathogenic variation of RFC1 repeat expansions: Implications for clinical diagnosis. 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