{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T13:04:28Z","timestamp":1770555868528,"version":"3.49.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T00:00:00Z","timestamp":1658361600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T00:00:00Z","timestamp":1658361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001721","name":"Rijksuniversiteit Groningen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001721","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Rosalind Franklin Fellowship"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recently, an intronic biallelic (AAGGG)<jats:sub>n<\/jats:sub> repeat expansion in <jats:italic>RFC1<\/jats:italic> was shown to be a cause of CANVAS and adult-onset ataxia in multiple populations. As the prevalence of the <jats:italic>RFC1<\/jats:italic> repeat expansion in Dutch cases was unknown, we retrospectively tested 9 putative CANVAS cases and two independent cohorts (A and B) of 395 and 222 adult-onset ataxia cases, respectively, using the previously published protocol and, for the first time optical genome mapping to determine the size of the expanded <jats:italic>RFC1<\/jats:italic> repeat. We identified the biallelic (AAGGG)<jats:sub>n<\/jats:sub> repeat expansion in 5\/9 (55%) putative CANVAS patients and in 10\/617 (1.6%; cohorts A\u2009+\u2009B) adult-onset ataxia patients. In addition to the AAGGG repeat motif, we observed a putative GAAGG repeat motif in the repeat expansion with unknown significance in two adult-onset ataxia patients. All the expanded (AAGGG)<jats:sub>n<\/jats:sub> repeats identified were in the range of 800\u20131299 repeat units. The intronic biallelic <jats:italic>RFC1<\/jats:italic> repeat expansion thus explains a number of the Dutch adult-onset ataxia cases that display the main clinical features of CANVAS, and particularly when ataxia is combined with neuropathy. The yield of screening for <jats:italic>RFC1<\/jats:italic> expansions in unselected cohorts is relatively low. To increase the current diagnostic yield in ataxia patients, we suggest adding <jats:italic>RFC1<\/jats:italic> screening to the genetic diagnostic workflow by using advanced techniques that attain long fragments.<\/jats:p>","DOI":"10.1007\/s00415-022-11275-9","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T19:03:47Z","timestamp":1658430227000},"page":"6086-6093","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Prevalence of intronic repeat expansions in RFC1 in Dutch patients with CANVAS and adult-onset ataxia"],"prefix":"10.1007","volume":"269","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4523-580X","authenticated-orcid":false,"given":"Fatemeh","family":"Ghorbani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jelkje","family":"de Boer-Bergsma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corien C.","family":"Verschuuren-Bemelmans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maartje","family":"Pennings","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eddy N.","family":"de Boer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Berry","family":"Kremer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Els K.","family":"Vanhoutte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeroen J.","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond","family":"van de Berg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik-Jan","family":"Kamsteeg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cleo C.","family":"van Diemen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helga","family":"Westers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart P.","family":"van de Warrenburg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4759-7006","authenticated-orcid":false,"given":"Dineke S.","family":"Verbeek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,7,21]]},"reference":[{"issue":"9","key":"11275_CR1","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/gim.2013.28","volume":"15","author":"S Jayadev","year":"2013","unstructured":"Jayadev S, Bird TD (2013) Hereditary ataxias: overview. 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