{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:32:40Z","timestamp":1790605960184,"version":"4.1.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,2]],"date-time":"2021-10-02T00:00:00Z","timestamp":1633132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,2]],"date-time":"2021-10-02T00:00:00Z","timestamp":1633132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The genetics of cerebellar ataxia is complex. Hundreds of causative genes have been identified, but only a few cause more than single cases. The spectrum of ataxia-causing genes differs considerably between populations. The aim of the study was to investigate the molecular epidemiology of ataxia in the Finnish population.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Patients and methods<\/jats:title>\n                <jats:p>All patients in hospital database were reviewed for the diagnosis of unspecified ataxia. Acquired ataxias and nongenetic ataxias such as those related to infection, trauma or stroke were excluded. Sixty patients with sporadic ataxia with unknown etiology and 36 patients with familial ataxia of unknown etiology were recruited in the study. Repeat expansions in the SCA genes (<jats:italic>ATXN1<\/jats:italic>, <jats:italic>2<\/jats:italic>, <jats:italic>3<\/jats:italic>, <jats:italic>7<\/jats:italic>, <jats:italic>8\/OS<\/jats:italic>, <jats:italic>CACNA1A, TBP<\/jats:italic>), <jats:italic>FXN<\/jats:italic>, and <jats:italic>RFC1<\/jats:italic> were determined. Point mutations in <jats:italic>POLG<\/jats:italic>, <jats:italic>SPG7<\/jats:italic> and in mitochondrial DNA (mtDNA) were investigated. In addition, DNA from 8 patients was exome sequenced.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>A genetic cause of ataxia was found in 33 patients (34.4%). Seven patients had a dominantly inherited repeat expansion in <jats:italic>ATXN8\/OS<\/jats:italic>. Ten patients had mitochondrial ataxia resulting from mutations in nuclear mitochondrial genes <jats:italic>POLG<\/jats:italic> or <jats:italic>RARS2<\/jats:italic>, or from a point mutation m.8561C\u2009&gt;\u2009G or a single deletion in mtDNA. Interestingly, five patients were biallelic for the recently identified pathogenic repeat expansion in <jats:italic>RFC1<\/jats:italic>. All the five patients presented with the phenotype of cerebellar ataxia, neuropathy, and vestibular areflexia (CANVAS). Moreover, screening of 54 patients with Charcot-Marie-Tooth neuropathy revealed four additional patients with biallelic repeat expansion in <jats:italic>RFC1<\/jats:italic>, but none of them had cerebellar symptoms.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Expansion in <jats:italic>ATXN8\/OS<\/jats:italic> results in the majority of dominant ataxias in Finland, while mutations in <jats:italic>RFC1<\/jats:italic> and <jats:italic>POLG<\/jats:italic> are the most common cause of recessive ataxias. Our results suggest that analysis of <jats:italic>RFC1<\/jats:italic> should be included in the routine diagnostics of idiopathic ataxia and Charcot-Marie-Tooth polyneuropathy.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12883-021-02409-z","type":"journal-article","created":{"date-parts":[[2021,10,2]],"date-time":"2021-10-02T05:17:16Z","timestamp":1633151836000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Molecular epidemiology of hereditary ataxia in Finland"],"prefix":"10.1186","volume":"21","author":[{"given":"Joonas","family":"Lipponen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seppo","family":"Helisalmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joose","family":"Raivo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari","family":"Siitonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Doi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harri","family":"Rusanen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Lehtilahti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mervi","family":"Ryytty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markku","family":"Laakso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiaki","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari","family":"Majamaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Kyt\u00f6vuori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,2]]},"reference":[{"issue":"4","key":"2409_CR1","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1136\/jnnp-2016-314863","volume":"88","author":"M Hadjivassiliou","year":"2017","unstructured":"Hadjivassiliou M, Martindale J, Shanmugarajah P, Gr\u00fcnewald RA, Sarrigianis PG, Beaucamp N, et al. 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All participants gave their informed consent for genetic analyses and for reporting the results. All clinical examinations were done according the WMA declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"382"}}