{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T19:30:38Z","timestamp":1793734238959,"version":"4.6.1"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T00:00:00Z","timestamp":1641772800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T00:00:00Z","timestamp":1641772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Yrj\u00f6 Jahnsson Foundation Finnish Parkinson Foundation Medical Research Center Oulu State research funding from Oulu University Hospital"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Parkinsons Dis."],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>An intronic expansion (AAGGG)<jats:sub>exp<\/jats:sub> in the <jats:italic>RFC1<\/jats:italic> gene has recently been shown to cause recessively inherited cerebellar ataxia, neuropathy, and vestibular areflexia syndrome and, furthermore, a few patients with ataxia and parkinsonism have been reported. We investigated 569 Finnish patients with medicated parkinsonism for <jats:italic>RFC1<\/jats:italic> and found biallelic (AAGGG)<jats:sub>exp<\/jats:sub> in three non-consanguineous patients with clinically confirmed Parkinson\u2019s disease without ataxia suggesting that <jats:italic>RFC1<\/jats:italic>-related disorders include Parkinson\u2019s disease as well.<\/jats:p>","DOI":"10.1038\/s41531-021-00275-7","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T11:02:59Z","timestamp":1641812579000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Biallelic expansion in RFC1 as a rare cause of Parkinson\u2019s disease"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2790-5646","authenticated-orcid":false,"given":"Laura","family":"Kyt\u00f6vuori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0183-9054","authenticated-orcid":false,"given":"Jussi","family":"Sipil\u00e4","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5807-2523","authenticated-orcid":false,"given":"Hiroshi","family":"Doi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anri","family":"Hurme-Niiranen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari","family":"Siitonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eriko","family":"Koshimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoko","family":"Miyatake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomichi","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiaki","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9070-3791","authenticated-orcid":false,"given":"Kari","family":"Majamaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,10]]},"reference":[{"key":"275_CR1","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/s41588-019-0372-4","volume":"51","author":"A Cortese","year":"2019","unstructured":"Cortese, A. et al. Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia. Nat. Genet. 51, 649\u2013658 (2019).","journal-title":"Nat. Genet."},{"key":"275_CR2","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.ajhg.2019.05.016","volume":"105","author":"H Rafehi","year":"2019","unstructured":"Rafehi, H. et al. Bioinformatics-based identification of expanded repeats: a non-reference intronic pentamer expansion in RFC1 causes CANVAS. Am. J. Hum. Genet. 105, 151\u2013165 (2019).","journal-title":"Am. J. Hum. Genet."},{"key":"275_CR3","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1093\/brain\/awz418","volume":"143","author":"A Cortese","year":"2020","unstructured":"Cortese, A. et al. Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion. Brain 143, 480\u2013490 (2020).","journal-title":"Brain"},{"key":"275_CR4","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1038\/s10038-020-0733-y","volume":"65","author":"H Nakamura","year":"2020","unstructured":"Nakamura, H. et al. Long-read sequencing identifies the pathogenic nucleotide repeat expansion in RFC1 in a Japanese case of CANVAS. J. Hum. Genet. 65, 475\u2013480 (2020).","journal-title":"J. Hum. Genet."},{"key":"275_CR5","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1002\/ana.25902","volume":"88","author":"L Wan","year":"2020","unstructured":"Wan, L. et al. Biallelic intronic AAGGG expansion of RFC1 is related to multiple system atrophy. Ann. Neurol. 88, 1132\u20131143 (2020).","journal-title":"Ann. Neurol."},{"key":"275_CR6","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1136\/jnnp-2020-325092","volume":"92","author":"R Sullivan","year":"2021","unstructured":"Sullivan, R. et al. RFC1-related ataxia is a mimic of early multiple system atrophy. J. Neurol. Neurosurg. Psychiatry 92, 444\u2013446 (2021).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"275_CR7","doi-asserted-by":"publisher","first-page":"e1369","DOI":"10.1212\/WNL.0000000000011528","volume":"96","author":"A Trasch\u00fctz","year":"2021","unstructured":"Trasch\u00fctz, A. et al. Natural history, phenotypic spectrum, and discriminative features of multisystemic RFC1 disease. Neurology 96, e1369\u2013e1382 (2021).","journal-title":"Neurology"},{"key":"275_CR8","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1002\/mds.28286","volume":"35","author":"G da Silva Schmitt","year":"2020","unstructured":"da Silva Schmitt, G. et al. Dopa-responsive parkinsonism in a patient with homozygous RFC1 expansions. Mov. Disord. 35, 1889\u20131890 (2020).","journal-title":"Mov. Disord."},{"key":"275_CR9","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1002\/mds.26424","volume":"30","author":"RB Postuma","year":"2015","unstructured":"Postuma, R. B. et al. MDS clinical diagnostic criteria for Parkinson\u2019s disease. Mov. Disord. 30, 1591\u20131601 (2015).","journal-title":"Mov. Disord."},{"key":"275_CR10","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1002\/mds.22024","volume":"23","author":"AS Havulinna","year":"2008","unstructured":"Havulinna, A. S. et al. Geographical variation of medicated parkinsonism in Finland during 1995 to 2000. Mov. Disord. 23, 1024\u20131031 (2008).","journal-title":"Mov. Disord."},{"key":"275_CR11","doi-asserted-by":"publisher","first-page":"e1009347","DOI":"10.1371\/journal.pgen.1009347","volume":"17","author":"S Kerminen","year":"2021","unstructured":"Kerminen, S. et al. Changes in the fine-scale genetic structure of Finland through the 20th century. PLoS Genet. 17, e1009347 (2021).","journal-title":"PLoS Genet."},{"key":"275_CR12","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-021-02409-z","volume":"21","author":"J Lipponen","year":"2021","unstructured":"Lipponen, J. et al. Molecular epidemiology of hereditary ataxia in Finland. BMC Neurol. 21, 382 (2021).","journal-title":"BMC Neurol."},{"key":"275_CR13","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/S1474-4422(19)30287-X","volume":"19","author":"C Blauwendraat","year":"2020","unstructured":"Blauwendraat, C., Nalls, M. A. & Singleton, A. B. The genetic architecture of Parkinson\u2019s disease. Lancet Neurol. 19, 170\u2013178 (2020).","journal-title":"Lancet Neurol."},{"key":"275_CR14","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1111\/j.1755-0998.2010.02847.x","volume":"10","author":"L Excoffier","year":"2010","unstructured":"Excoffier, L. & Lischer, H. E. Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows. Mol. Ecol. Resour. 10, 564\u2013567 (2010).","journal-title":"Mol. Ecol. Resour."},{"key":"275_CR15","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.neurobiolaging.2017.01.019","volume":"53","author":"A Siitonen","year":"2017","unstructured":"Siitonen, A. et al. Genetics of early-onset Parkinson\u2019s disease in Finland: exome sequencing and genome-wide association study. Neurobiol. Aging 53, 195\u2013e7 (2017).","journal-title":"Neurobiol. Aging"},{"key":"275_CR16","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/ng.806","volume":"43","author":"MA DePristo","year":"2011","unstructured":"DePristo, M. A. et al. A framework for variation discovery and genotyping using next generation DNA sequencing data. Nat. Genet. 43, 491\u2013498 (2011).","journal-title":"Nat. Genet."},{"key":"275_CR17","unstructured":"Van der Auwera, G. A. & O\u2019Connor B. D. Genomics in the Cloud: Using Docker, GATK, and WDL in Terra (O\u2019Reilly Media, Sebastopol, 2020)."},{"key":"275_CR18","first-page":"7","volume":"81","author":"M Fromer","year":"2014","unstructured":"Fromer, M. & Purcell, S. M. Using XHMM software to detect copy number variation in whole\u2010exome sequencing data. Curr. Protoc. Hum. Genet. 81, 7\u201323 (2014).","journal-title":"Curr. Protoc. Hum. Genet."},{"key":"275_CR19","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.jmoldx.2019.08.009","volume":"22","author":"S V\u00e4lipakka","year":"2020","unstructured":"V\u00e4lipakka, S. et al. Improving copy number variant detection from sequencing data with a combination of programs and a predictive model. J. Mol. Diagn. 22, 40\u201349 (2020).","journal-title":"J. Mol. Diagn."},{"key":"275_CR20","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/nmeth.3930","volume":"13","author":"M Loose","year":"2016","unstructured":"Loose, M., Malla, S. & Stout, M. Real-time selective sequencing using nanopore technology. Nat. Methods 13, 751\u2013754 (2016).","journal-title":"Nat. Methods"}],"container-title":["npj Parkinson's Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41531-021-00275-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41531-021-00275-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41531-021-00275-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T14:06:10Z","timestamp":1669298770000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41531-021-00275-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,10]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["275"],"URL":"https:\/\/doi.org\/10.1038\/s41531-021-00275-7","relation":{},"ISSN":["2373-8057"],"issn-type":[{"value":"2373-8057","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,10]]},"assertion":[{"value":"16 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 December 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 January 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6"}}