{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T02:14:44Z","timestamp":1780107284037,"version":"3.54.0"},"reference-count":37,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T00:00:00Z","timestamp":1664064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171256"],"award-info":[{"award-number":["82171256"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U20A20355"],"award-info":[{"award-number":["U20A20355"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and purpose<\/jats:title><jats:p><jats:italic>NOTCH2NLC<\/jats:italic> GGC repeat expansions have been identified to be associated with essential tremor (ET). Our aim was to characterize ET patients with <jats:italic>NOTCH2NLC<\/jats:italic> repeat expansions versus non\u2010expansions and describe distinctive clinical features of repeat expanded patients with long\u2010term follow\u2010up according to the new tremor classification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Participants included 597 ET pedigrees, 412 sporadic cases and 1085 healthy controls. Repeat expansions of GGC in <jats:italic>NOTCH2NLC<\/jats:italic> were screened, and comprehensive clinical features were investigated. A longitudinal clinical assessment and reclassification were performed in <jats:italic>NOTCH2NLC<\/jats:italic> expanded patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 27 ET pedigrees (27\/597) and three sporadic patients (3\/412) were identified with pathogenic <jats:italic>NOTCH2NLC<\/jats:italic> GGC repeat expansions (\u226560 repeats). Intermediate\u2010length GGC repeats (41\u201359 repeats) were found in four sporadic ET cases and one control subject, and the frequency was higher than that in control participants (4\/412 vs. 1\/1085, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.022). About 46 ET patients (43 familial cases from 27 pedigrees and three sporadic cases) with <jats:italic>NOTCH2NLC<\/jats:italic> GGC repeat expansions had higher Essential Tremor Rating Assessment Scale I, Essential Tremor Rating Assessment Scale II and Non\u2010Motor Symptoms Scale scores and lower Mini\u2010Mental State Examination scores than the patients without expansions. Patients with pathogenic GGC repeats were reclassified as pure ET (25\/46), ET\u2010plus (11\/46) and ET\u2010neuronal intranuclear inclusion disease (10\/46) subgroups at 2\u20138\u2009years of follow\u2010up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results further supported that <jats:italic>NOTCH2NLC<\/jats:italic> GGC repeat expansions were associated with ET. Patients with pathogenic GGC repeats presented with more severe motor and non\u2010motor symptoms. Further long\u2010term follow\u2010up and subtype studies will help to define the role of <jats:italic>NOTCH2NLC<\/jats:italic> in ET.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15552","type":"journal-article","created":{"date-parts":[[2022,9,10]],"date-time":"2022-09-10T08:00:13Z","timestamp":1662796813000},"page":"3600-3610","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Clinical features and reclassification of essential tremor with <scp><i>NOTCH2NLC<\/i> GGC<\/scp> repeat expansions based on a long\u2010term follow\u2010up"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7325-5720","authenticated-orcid":false,"given":"Xun","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Geriatric Neurology, Xiangya Hospital Central South University  Changsha 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