{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T08:18:36Z","timestamp":1773044316089,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["111\u20102314\u2010B\u2010075\u2010065"],"award-info":[{"award-number":["111\u20102314\u2010B\u2010075\u2010065"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["112\u20102314\u2010B\u2010075\u2010034\u2010MY3"],"award-info":[{"award-number":["112\u20102314\u2010B\u2010075\u2010034\u2010MY3"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["112\u20102314\u2010B\u2010075\u2010057"],"award-info":[{"award-number":["112\u20102314\u2010B\u2010075\u2010057"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG3L1651"],"award-info":[{"award-number":["CMRPG3L1651"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder caused by\n                      <jats:italic>NOTCH2NLC<\/jats:italic>\n                      GGC repeat expansions, with heterogeneous clinical manifestations, including parkinsonism. Recent studies have identified\n                      <jats:italic>NOTCH2NLC<\/jats:italic>\n                      repeat expansions in patients with Parkinson's disease (PD) and atypical parkinsonism (aPM), suggesting a potential genetic contribution. However, it remains unclear whether such cases represent NIID\u2010related parkinsonism or typical PD. To address this, we screened\n                      <jats:italic>NOTCH2NLC<\/jats:italic>\n                      repeat expansions in a parkinsonian cohort and analyzed associated clinical and neuroimaging features.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We examined 1017 unrelated patients with PD, 115 with aPM, 11 with multiple system atrophy, six with progressive supranuclear palsy, three with dementia with Lewy bodies, and 321 healthy controls.\n                      <jats:italic>NOTCH2NLC<\/jats:italic>\n                      GGC repeat expansions were detected using repeat\u2010primed PCR and amplicon length analysis. Clinical data and neuroimaging findings were comprehensively reviewed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Pathological\n                      <jats:italic>NOTCH2NLC<\/jats:italic>\n                      repeat expansions were identified in four patients with aPM and none with PD or in controls, with significantly higher frequency in aPM than in PD. An additional affected family member was also identified. All five patients showed clinical or neuroimaging features suggestive of NIID, including white matter hyperintensities in the paravermis and\/or corticomedullary junction, curvilinear hyperintensities on diffusion\u2010weighted imaging. Skin biopsies in two patients revealed eosinophilic, p62\u2010positive intranuclear inclusions in the sweat gland cells and fibroblasts. No patient responded well to levodopa. TRODAT scans revealed normal findings in three patients, symmetric dopaminergic deficits in one, and asymmetric deficits in another.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      <jats:italic>NOTCH2NLC<\/jats:italic>\n                      repeat expansions appear to be more frequently associated with aPM with NIID\u2010like features than with typical PD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70147","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T05:54:06Z","timestamp":1753422846000},"page":"2181-2192","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<i>NOTCH2NLC<\/i>\n                    Repeat Expansions in Parkinsonian Disorders: Clinical and Neuroimaging Characteristics"],"prefix":"10.1002","volume":"12","author":[{"given":"Han\u2010Lin","family":"Chiang","sequence":"first","affiliation":[{"name":"Department of Neurology Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Department of Neurology National Yang Ming Chiao Tung University School of Medicine  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang\u2010Yang","family":"Jih","sequence":"additional","affiliation":[{"name":"Department of Neurology Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Department of Neurology National Yang Ming Chiao Tung University School of Medicine  Taipei Taiwan"},{"name":"Department and Institute of Physiology National Yang Ming Chiao Tung University School of Medicine  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng\u2010Tsung","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Neurology Taipei Veterans General Hospital  Taipei 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Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9644-2086","authenticated-orcid":false,"given":"Yi\u2010Chu","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Neurology Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Department of Neurology National Yang Ming Chiao Tung University School of Medicine  Taipei Taiwan"},{"name":"Brain Research Center National Yang Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1191-2542","authenticated-orcid":false,"given":"Yih\u2010Ru","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center  Taoyuan Taiwan"},{"name":"Department of Neurology, College of Medicine Chang Gung University  Taoyuan 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