{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T21:43:21Z","timestamp":1771969401733,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS069719"],"award-info":[{"award-number":["R01 NS069719"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P50 AG005136, K08AG065426"],"award-info":[{"award-number":["P50 AG005136, K08AG065426"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:p>Biallelic mutations in <jats:italic>POLR3A<\/jats:italic> have been associated with childhood\u2010onset hypomyelinating leukodystrophies and adolescent\u2010to\u2010adult\u2010onset spastic ataxia, the latter of which has been linked to the intronic variant c.1909 + 22G&gt;A. We report a case of  adult\u2010onset spastic ataxia in a 75\u2010year\u2010old man, being a compound heterozygous carrier of this variant, whose brain and spinal cord were for the first time investigated by neuropathological examination. We describe prominent degeneration of the posterior columns, spinocerebellar tracts, and anterior corticospinal tracts of the spinal cord in a pattern resembling Friedreich's ataxia, with a notable lack of significant white matter pathology throughout the brain, in marked contrast with childhood\u2010onset cases. Immunohistochemical examination for the POLR3A protein demonstrated no apparent differences in localization or staining intensity between the proband and an age\u2010matched control subject. We demonstrate the clinicopathologic description of <jats:italic>POLR3A<\/jats:italic>\u2010related neurodegenerative disease and also mention the differential diagnosis of the childhood\u2010onset hypomyelinating leukodystrophy and late\u2010onset spastic ataxia phenotypes.<\/jats:p>","DOI":"10.1111\/neup.12775","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T00:09:52Z","timestamp":1636502992000},"page":"58-65","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Spinal cord\u2010predominant neuropathology in an adult\u2010onset case of <scp><i>POLR3A<\/i><\/scp>\u2010related spastic ataxia"],"prefix":"10.1111","volume":"42","author":[{"given":"Trevor M.","family":"Sytsma","sequence":"first","affiliation":[{"name":"Neuropathology Division, Department of Laboratory Medicine and Pathology University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong\u2010Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley","family":"Rolf","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Medicine University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Dorschner","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Medicine University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suman","family":"Jayadev","sequence":"additional","affiliation":[{"name":"Neuropathology Division, Department of Laboratory Medicine and Pathology University of Washington School of Medicine  Seattle Washington USA"},{"name":"Department of Neurology University of Washington School of Medicine  Seattle Washington USA"},{"name":"Division of Medical Genetics, Department of Medicine University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. 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