{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:16:46Z","timestamp":1789784206040,"version":"4.0.1"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T00:00:00Z","timestamp":1658880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"French patients\u2019 association"},{"DOI":"10.13039\/100007393","name":"French Association against Myopathies","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007393","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is an inherited late-onset neurological disease caused by bi-allelic AAGGG pentanucleotide expansions within intron 2 of RFC1. Despite extensive studies, the pathophysiological mechanism of these intronic expansions remains elusive.<\/jats:p>\n               <jats:p>We screened by clinical exome sequencing two unrelated patients presenting with late-onset ataxia. A repeat-primer polymerase chain reaction was used for RFC1 AAGGG intronic expansion identification. RFC1 mRNA expression was assessed by quantitative reverse transcription\u2013polymerase chain reaction.<\/jats:p>\n               <jats:p>We identified the first two CANVAS affected patients who are compound heterozygous for RFC1 truncating variants (p.Arg388* and c.575delA, respectively) and a pathological AAGGG expansion. RFC1 expression studies in whole blood showed a significant reduction of RFC1 mRNA for both patients compared to three patients with bi-allelic RFC1 expansions.<\/jats:p>\n               <jats:p>In conclusion, this observation provides clues that suggest bi-allelic RFC1 conditional loss-of-function as the cause of the disease.<\/jats:p>","DOI":"10.1093\/brain\/awac280","type":"journal-article","created":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T04:19:24Z","timestamp":1658895564000},"page":"3770-3775","source":"Crossref","is-referenced-by-count":41,"title":["RFC1 nonsense and frameshift variants cause CANVAS: clues for an unsolved pathophysiology"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6445-6347","authenticated-orcid":false,"given":"Mehdi","family":"Benkirane","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, Institut Universitaire de Recherche Clinique (IURC), Montpellier Hospital , Montpellier , 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