{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:16:42Z","timestamp":1789784202146,"version":"4.0.1"},"reference-count":10,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T00:00:00Z","timestamp":1667433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/00851"],"award-info":[{"award-number":["PI20\/00851"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The biallelic pathogenic repeat (AAGGG)\n                    <jats:sub>400\u20132000<\/jats:sub>\n                    intronic expansion in the\n                    <jats:italic>RFC1<\/jats:italic>\n                    gene has been recently described as the cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) and as a major cause of late\u2010onset ataxia. Since then, many heterozygous carriers have been identified, with an estimated allele frequency of 0.7% to 4% in the healthy population. Here, we describe in two affected CANVAS sisters the presence of the nonsense c.724C\u2009&gt;\u2009T p.(Arg242*) variant in compound heterozygosity with the pathogenic repeat expansion in the\n                    <jats:italic>RFC1<\/jats:italic>\n                    gene. Further RNA analysis demonstrated a reduced expression of the p.Arg242* allele in patients confirming an efficient nonsense\u2010mediated mRNA decay. We also highlight the importance of considering the sequencing of the\n                    <jats:italic>RFC1<\/jats:italic>\n                    gene for the diagnosis, especially in patients with CANVAS diagnosis carriers of the AAGGG repeat expansion.\n                  <\/jats:p>","DOI":"10.1111\/cge.14249","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T09:42:36Z","timestamp":1665999756000},"page":"236-241","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["New Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome cases are caused by the presence of a nonsense variant in compound heterozygosity with the pathogenic repeat expansion in the\n                    <scp>\n                      <i>RFC1<\/i>\n                    <\/scp>\n                    gene"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4806-9774","authenticated-orcid":false,"given":"Ana","family":"Arteche\u2010L\u00f3pez","sequence":"first","affiliation":[{"name":"Genetics Department 12 de Octubre University Hospital  Madrid Spain"},{"name":"UDISGEN (Unidad de Dismorfolog\u00eda y Gen\u00e9tica) 12 de Octubre University Hospital  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almudena","family":"Avila\u2010Fernandez","sequence":"additional","affiliation":[{"name":"Genetics Department, Health Research Institute\u2013Jimenez Diaz Foundation University Hospital Universidad Aut\u00f3noma de Madrid (IIS\u2010FJD\u2010UAM)  Madrid Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases (CIBERER) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Damian","sequence":"additional","affiliation":[{"name":"Genetics Department, Health Research Institute\u2013Jimenez Diaz Foundation University Hospital Universidad Aut\u00f3noma de Madrid (IIS\u2010FJD\u2010UAM)  Madrid Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases (CIBERER) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Soengas\u2010Gonda","sequence":"additional","affiliation":[{"name":"Genetics Department 12 de Octubre University Hospital  Madrid Spain"},{"name":"UDISGEN (Unidad de Dismorfolog\u00eda y Gen\u00e9tica) 12 de Octubre University Hospital  Madrid Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases (CIBERER) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2749-2709","authenticated-orcid":false,"given":"Rub\u00e9n P\u00e9rez","family":"de la Fuente","sequence":"additional","affiliation":[{"name":"Genetics Department 12 de Octubre University Hospital  Madrid Spain"},{"name":"UDISGEN (Unidad de Dismorfolog\u00eda y Gen\u00e9tica) 12 de Octubre University Hospital  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia Ramos","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Genetics Department 12 de Octubre University Hospital  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas Gallego","family":"Merlo","sequence":"additional","affiliation":[{"name":"Genetics Department, Health Research Institute\u2013Jimenez Diaz Foundation University Hospital Universidad Aut\u00f3noma de Madrid (IIS\u2010FJD\u2010UAM)  Madrid Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases (CIBERER) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Horcajada","family":"Burgos","sequence":"additional","affiliation":[{"name":"Genetics Department, Health Research Institute\u2013Jimenez Diaz Foundation University Hospital Universidad Aut\u00f3noma de Madrid (IIS\u2010FJD\u2010UAM)  Madrid Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases (CIBERER) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Cemill\u00e1n","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Neurology Service Severo Ochoa University Hospital  Legan\u00e9s Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Miguel Lezana","family":"Rosales","sequence":"additional","affiliation":[{"name":"Genetics Department 12 de Octubre University Hospital  Madrid Spain"},{"name":"UDISGEN (Unidad de Dismorfolog\u00eda y Gen\u00e9tica) 12 de Octubre University Hospital  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Francisco Gonz\u00e1lez","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Neurology Service 12 de Octubre University Hospital  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4420-5214","authenticated-orcid":false,"given":"Juan Francisco","family":"Quesada\u2010Espinosa","sequence":"additional","affiliation":[{"name":"Genetics Department 12 de Octubre University Hospital  Madrid Spain"},{"name":"UDISGEN (Unidad de Dismorfolog\u00eda y Gen\u00e9tica) 12 de Octubre University Hospital  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Corton","sequence":"additional","affiliation":[{"name":"Genetics Department, Health Research Institute\u2013Jimenez Diaz Foundation University Hospital Universidad Aut\u00f3noma de Madrid (IIS\u2010FJD\u2010UAM)  Madrid Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases (CIBERER) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Paz","family":"Guerrero\u2010Molina","sequence":"additional","affiliation":[{"name":"Neurology Service 12 de Octubre University Hospital  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz418"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/practneurol-2020-002822"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0372-4"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab363"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.05.016"},{"issue":"4","key":"e_1_2_10_7_1","first-page":"16","article-title":"RFC1 nonsense and frameshift variants cause CANVAS: clues for an unsolved pathophysiology","volume":"139","author":"Benkirane M","year":"2022","journal-title":"Brain"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_9_1","unstructured":"RafehiH SzmulewiczDJ BennettMF SobreiraNL PopeK SmithKR et al.Validation of new bioinformatic tools to identify expanded repeats: a non\u2010reference intronic pentamer expansion in RFC1 causes CANVAS. bioRxiv2019;597781."},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-020-00398-z"},{"issue":"5","key":"e_1_2_10_11_1","first-page":"257","article-title":"Recessive cerebellar and afferent ataxias\u2014clinical challenges and future directions","volume":"18","author":"Beaudin M","year":"2022","journal-title":"Nat Rev"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14249","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.14249","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14249","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T09:27:37Z","timestamp":1692523657000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14249"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,3]]},"references-count":10,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["10.1111\/cge.14249"],"URL":"https:\/\/doi.org\/10.1111\/cge.14249","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14249\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14249\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14249\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14249\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14249\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14249\/v1\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,3]]},"assertion":[{"value":"2022-07-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}