{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:51:51Z","timestamp":1791359511966,"version":"4.3.1"},"reference-count":53,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Association between monoallelic\n STUB1<\/jats:italic>\n variant and expanded\n ATXN8OS<\/jats:italic>\n alleles was recently reported, suggesting a pathogenic interaction that may influence spinocerebellar ataxia type 48 (SCA48) phenotype.\n <\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n \n We investigated the frequency and clinical impact of\n ATXN8OS<\/jats:italic>\n in a large cohort of\n STUB1<\/jats:italic>\n carriers compared to individuals with other ataxias and controls.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Ataxic individuals and controls from the SPATAX\/BIOMOV cohorts (Paris Brain Institute) were screened for\n ATXN8OS<\/jats:italic>\n and other CAG expansions using polymerase chain reaction (PCR)\/repeat\u2010prime PCR (RP\u2010PCR) and\n ExpansionHunter<\/jats:italic>\n .\n STUB1<\/jats:italic>\n carriers underwent whole\u2010genome or exome sequencing.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Our cohort comprised 12 biallelic\n STUB1<\/jats:italic>\n carriers (SCAR16) and 67 monoallelic\n STUB1<\/jats:italic>\n carriers (SCA48) without other causative variants.\n ATXN8OS<\/jats:italic>\n expansions (84\u2013177 CTA\/CTG repeats) were identified in seven SCA48 individuals (10.5%) who exhibited earlier onset (median age 28 vs. 47\u2009years,\n P<\/jats:italic>\n \u2009<\u20090.001) compared to other SCA48 individuals but with similar clinical presentation.\n ATXN8OS<\/jats:italic>\n expansions were also found in two healthy controls older than 50\u2009years (2\/286, 0.7%) and in eight index cases with autosomal dominant ataxia (8\/400, 2%), including four carrying another molecular diagnosis without any effect on the phenotype. Other intermediate expansions were identified in individuals with SCA48: seven (10.5%) carried intermediate\n TBP<\/jats:italic>\n alleles (40\u201346 CAG\/CAA) without any effect on dementia prevalence; four carried intermediate\n HTT<\/jats:italic>\n alleles (28\u201329 CAG); and three carried intermediate\n ATXN1<\/jats:italic>\n expansions (38 CAG).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n ATXN8OS<\/jats:italic>\n intermediate expansion acts as a genetic modifier in SCA48 but not in other ataxias. Moreover, expanded intermediate alleles in neurodegenerative disease genes were present in one\u2010third of SCA48 individuals. These alleles may increase polyglutamine burden, potentially saturating STUB1 E3 ubiquitin ligase activity. \u00a9 2026 The Author(s).\n Movement Disorders<\/jats:italic>\n published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mds.70534","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:49:38Z","timestamp":1790056178000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ATXN8OS<\/scp>\n Intermediate Expansion Acts as a Genetic Modifier in Spinocerebellar Ataxia Type 48 (\n SCA48<\/scp>\n \/\n \n STUB1<\/i>\n <\/scp>\n )"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9569-9229","authenticated-orcid":false,"given":"Charlotte","family":"Mouraux","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, Paris Brain Institute\u2014ICM, Inserm, CNRS, APHP, Piti\u00e9\u2010Salp\u00eatri\u00e8re University Hospital Paris France"},{"name":"GIGA\u2014CRC\u2014Rare Movement Disorders Research Group University of Li\u00e8ge Li\u00e8ge Belgium"},{"name":"Department of Human Genetics University Hospital of Li\u00e8ge Li\u00e8ge Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4279-7252","authenticated-orcid":false,"given":"Jean\u2010Loup","family":"M\u00e9reaux","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Paris Brain Institute\u2014ICM, Inserm, CNRS, APHP, Piti\u00e9\u2010Salp\u00eatri\u00e8re University Hospital Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5821-8462","authenticated-orcid":false,"given":"Claire\u2010Sophie","family":"Davoine","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Paris Brain Institute\u2014ICM, Inserm, CNRS, APHP, 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