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Recently, expanded GAA repeats (\u2265250 repeat units) in intron 1 of <jats:italic>FGF14<\/jats:italic> have been shown to be responsible for spinocerebellar ataxia type 27B (SCA27B), a late-onset ataxia with an autosomal dominant inheritance. Patients with SCA27B may also exhibit autonomic nervous system dysfunction, potentially overlapping with the clinical presentations of MSA patients. In this study, to explore the possible involvement of expanded GAA repeats in MSA, we investigated the frequencies of expanded GAA repeats in <jats:italic>FGF14<\/jats:italic> in 548 patients with MSA, 476 patients with undiagnosed ataxia, and 455 healthy individuals. To fully characterize the structures of the expanded GAA repeats, long-range PCR products suggesting the expansion of GAA repeats were further analyzed using a long-read sequencer. Of the 548 Japanese MSA patients, we identified one MSA patient (0.2%) carrying an expanded repeat with (GAA)<jats:sub>\u2265250<\/jats:sub>. Among the 476 individuals with undiagnosed ataxia, (GAA)<jats:sub>\u2265250<\/jats:sub> was observed in six (1.3%); this frequency was higher than that in healthy individuals (0.2%). The clinical characteristics of the MSA patient with (GAA)<jats:sub>\u2265250<\/jats:sub> were consistent with those of MSA, but not with SCA27B. Further research is warranted to explore the possibility of the potential association of expanded GAA repeats in <jats:italic>FGF14<\/jats:italic> with MSA.<\/jats:p>","DOI":"10.1038\/s41431-024-01743-3","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T17:01:07Z","timestamp":1732726867000},"page":"325-333","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Frequency of FGF14 intronic GAA repeat expansion in patients with multiple system atrophy and undiagnosed ataxia in the Japanese 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This study was approved by the institutional review board of the University of Tokyo and participating institutions.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}}]}}