{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:43:41Z","timestamp":1791323021519,"version":"4.3.1"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002803","name":"Fondazione Cariplo","doi-asserted-by":"publisher","award":["2019\u20101836"],"award-info":[{"award-number":["2019\u20101836"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100022720","name":"Fondazione Regionale per la Ricerca Biomedica","doi-asserted-by":"publisher","award":["1751723"],"award-info":[{"award-number":["1751723"]}],"id":[{"id":"10.13039\/501100022720","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/T001712\/1"],"award-info":[{"award-number":["MR\/T001712\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["20229MMHXP"],"award-info":[{"award-number":["20229MMHXP"]}],"id":[{"id":"10.13039\/501100021856","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":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Biallelic intronic AAGGG repeat expansions in the replication factor complex subunit 1 (<jats:italic>RFC1<\/jats:italic>) gene were identified as the leading cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome. Patients exhibit significant clinical heterogeneity and variable disease course, but no potential biomarker has been identified to date.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>In this multicenter cross\u2010sectional study, we aimed to evaluate neurofilament light (NfL) chain serum levels in a cohort of <jats:italic>RFC1<\/jats:italic> disease patients and to correlate NfL serum concentrations with clinical phenotype and disease severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixty\u2010one patients with genetically confirmed <jats:italic>RFC1<\/jats:italic> disease and 48 healthy controls (HCs) were enrolled from six neurological centers. Serum NfL concentration was measured using the single molecule array assay technique.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Serum NfL concentration was significantly higher in patients with <jats:italic>RFC1<\/jats:italic> disease compared to age\u2010 and\u2010sex\u2010matched HCs (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001). NfL level showed a moderate correlation with age in both HCs (<jats:italic>r<\/jats:italic>\u2009=\u20090.4353, <jats:italic>P<\/jats:italic>\u2009=\u20090.0020) and patients (<jats:italic>r<\/jats:italic>\u2009=\u20090.4092, <jats:italic>P<\/jats:italic>\u2009=\u20090.0011). Mean NfL concentration appeared to be significantly higher in patients with cerebellar involvement compared to patients without cerebellar dysfunction (27.88 vs. 21.84\u2009pg\/mL, <jats:italic>P<\/jats:italic>\u2009=\u20090.0081). The association between cerebellar involvement and NfL remained significant after controlling for age and sex (\u03b2\u2009=\u20090.260, <jats:italic>P<\/jats:italic>\u2009=\u20090.034).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Serum NfL levels are significantly higher in patients with <jats:italic>RFC1<\/jats:italic> disease compared to HCs and correlate with cerebellar involvement. Longitudinal studies are warranted to assess its change over time.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29680","type":"journal-article","created":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T12:54:53Z","timestamp":1701867293000},"page":"209-214","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Serum Neurofilament Light Chain in Replication Factor Complex Subunit 1 <scp>CANVAS<\/scp> and Disease Spectrum"],"prefix":"10.1002","volume":"39","author":[{"given":"Ilaria","family":"Quartesan","sequence":"first","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"},{"name":"IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Vegezzi","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"},{"name":"IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Curr\u00f2","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"},{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Heslegrave","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease UCL Queen Square Institute of Neurology  London United Kingdom"},{"name":"UK Dementia Research Institute at UCL  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Pisciotta","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Iruzubieta","sequence":"additional","affiliation":[{"name":"Neurology Department, Donostia University Hospital Osakidetza, and Biodonostia Health Research Institute\u2010UPV\u2010EHU  San Sebasti\u00e1n Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Salvalaggio","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Padova  Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gorka","family":"Fern\u00e1ndez\u2010Eulate","sequence":"additional","affiliation":[{"name":"Neuro\u2010myology Department, Institut de Myologie, Piti\u00e9\u2010Salp\u00eatri\u00e9re Hospital APHP, Sorbonne University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Dominik","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Rugginini","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Manini","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London United Kingdom"},{"name":"Department of Neurology and Laboratory of Neuroscience IRCCS Istituto Auxologico Italiano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Abati","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London United Kingdom"},{"name":"Department of Pathophysiology and Transplantation (DEPT) University of Milan  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Facchini","sequence":"additional","affiliation":[{"name":"IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Manso","sequence":"additional","affiliation":[{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Albajar","sequence":"additional","affiliation":[{"name":"Neurology Department, Donostia University Hospital Osakidetza, and Biodonostia Health Research Institute\u2010UPV\u2010EHU  San Sebasti\u00e1n Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhiannon","family":"Laban","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at UCL  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander M.","family":"Rossor","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Pichiecchio","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"},{"name":"IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Cosentino","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"},{"name":"IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Saveri","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9167-1878","authenticated-orcid":false,"given":"Ettore","family":"Salsano","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Andreetta","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0600-6820","authenticated-orcid":false,"given":"Enza M.","family":"Valente","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"},{"name":"IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease UCL Queen Square Institute of Neurology  London United Kingdom"},{"name":"UK Dementia Research Institute at UCL  London United Kingdom"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"},{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology The Sahlgrenska Academy at the University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Hong Kong Center for Neurodegenerative Diseases Clear Water Bay  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Giunti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neuroscience UCL Queen Square Institute of Neurology  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Stojkovic","sequence":"additional","affiliation":[{"name":"Neuro\u2010myology Department, Institut de Myologie, Piti\u00e9\u2010Salp\u00eatri\u00e9re Hospital APHP, Sorbonne University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Briani","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Padova  Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolfo","family":"L\u00f3pez de Munain","sequence":"additional","affiliation":[{"name":"Neurology Department, Donostia University Hospital Osakidetza, and Biodonostia Health Research Institute\u2010UPV\u2010EHU  San Sebasti\u00e1n Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Pareyson","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"Reilly","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2866-7777","authenticated-orcid":false,"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Tassorelli","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"},{"name":"IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2208-5311","authenticated-orcid":false,"given":"Andrea","family":"Cortese","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"},{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0372-4"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.05.016"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz418"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.14802\/jmd.21117"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jns.12515"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15717"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23620-z"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004932"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14689"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011090"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-022-05846-8"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28783"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200257"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac003"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-021-10835-9"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac253"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012945"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000207088"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-021-01257-4"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-021-10499-5"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab449"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.13051"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28711"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2021.105311"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.29680","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T09:26:24Z","timestamp":1760952384000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.29680"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,6]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/mds.29680"],"URL":"https:\/\/doi.org\/10.1002\/mds.29680","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,6]]},"assertion":[{"value":"2023-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}