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Its underlying genetic cause was recently mapped to the <jats:italic>RFC1<\/jats:italic> gene, and additional reports have expanded on the phenotypic manifestations related to <jats:italic>RFC1<\/jats:italic>, although little is known about the pattern and extent of structural brain abnormalities in this condition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim is to characterize the structural signature of brain damage in <jats:italic>RFC1<\/jats:italic>\u2010related disorder, correlating the findings with clinical symptoms and normal brain <jats:italic>RFC1<\/jats:italic> expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We recruited 22 individuals with molecular confirmation of <jats:italic>RFC1<\/jats:italic> expansions and submitted them to high\u2010resolution 3T magnetic resonance imaging scans. We performed multimodal analyses to assess separately cerebral and cerebellar abnormalities within gray and white matter (WM). The results were compared with a group of 22 age\u2010 and sex\u2010matched controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The mean age and disease duration of patients were 62.8 and 10.9\u2009years, respectively. Ataxia, sensory neuronopathy, and vestibular areflexia were the most frequent manifestations, but parkinsonism and pyramidal signs were also noticed. We found that <jats:italic>RFC1<\/jats:italic>\u2010related disorder is characterized by widespread and relatively symmetric cerebellar and basal ganglia atrophy. There is brainstem volumetric reduction along all its segments. Cerebral WM is also involved\u2014mostly the corpus callosum and deep tracts, but cerebral cortical damage is rather restricted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study adds new relevant insights into the pathophysiological mechanisms of <jats:italic>RFC1<\/jats:italic>\u2010related disorder. It should no longer be considered a purely cerebellar and sensory pathway disorder. Basal ganglia and deep cerebral WM are additional targets of damage. \u00a9 2021 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.28711","type":"journal-article","created":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T09:17:02Z","timestamp":1625822222000},"page":"2634-2641","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Brain Structural Signature of <scp><i>RFC1<\/i><\/scp>\u2010Related Disorder"],"prefix":"10.1002","volume":"36","author":[{"given":"Paula Camila A.A.P.","family":"Matos","sequence":"first","affiliation":[{"name":"Division of General Neurology and Ataxia Unit, Department of Neurology Federal University of S\u00e3o Paulo (UNIFESP)  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8453-0313","authenticated-orcid":false,"given":"Thiago 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