{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:42:51Z","timestamp":1789472571495,"version":"build-2803163510"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,31]],"date-time":"2021-10-31T00:00:00Z","timestamp":1635638400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2021,10,31]],"date-time":"2021-10-31T00:00:00Z","timestamp":1635638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2022,1]]},"DOI":"10.1007\/s12035-021-02616-2","type":"journal-article","created":{"date-parts":[[2021,10,31]],"date-time":"2021-10-31T09:02:30Z","timestamp":1635670950000},"page":"523-534","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["The Phenotypes and Mechanisms of NOTCH2NLC-Related GGC Repeat Expansion Disorders: a Comprehensive Review"],"prefix":"10.1007","volume":"59","author":[{"given":"Xiu-Rong","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei-Sha","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3658-3928","authenticated-orcid":false,"given":"Ji-Feng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,31]]},"reference":[{"issue":"6","key":"2616_CR1","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1016\/j.cell.2018.03.067","volume":"173","author":"IK Suzuki","year":"2018","unstructured":"Suzuki IK et al (2018) Human-specific NOTCH2NL Genes expand cortical neurogenesis through Delta\/Notch regulation. Cell 173(6):1370\u20131384.e16","journal-title":"Cell"},{"issue":"6","key":"2616_CR2","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1016\/j.cell.2018.03.051","volume":"173","author":"IT Fiddes","year":"2018","unstructured":"Fiddes IT et al (2018) Human-specific NOTCH2NL genes affect Notch signaling and cortical neurogenesis. Cell 173(6):1356\u20131369.e22","journal-title":"Cell"},{"issue":"1","key":"2616_CR3","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1128\/MCB.24.1.58-70.2004","volume":"24","author":"Z Duan","year":"2004","unstructured":"Duan Z et al (2004) A novel notch protein, N2N, targeted by neutrophil elastase and implicated in hereditary neutropenia. Mol Cell Biol 24(1):58\u201370","journal-title":"Mol Cell Biol"},{"issue":"9","key":"2616_CR4","doi-asserted-by":"publisher","first-page":"2531","DOI":"10.1093\/molbev\/msaa104","volume":"37","author":"GA Lodewijk","year":"2020","unstructured":"Lodewijk GA et al (2020) Evolution of human brain size-associated NOTCH2NL genes proceeds toward reduced protein levels. Mol Biol Evol 37(9):2531\u20132548","journal-title":"Mol Biol Evol"},{"issue":"7","key":"2616_CR5","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1007\/s00439-019-02018-4","volume":"138","author":"IT Fiddes","year":"2019","unstructured":"Fiddes IT et al (2019) Paired involvement of human-specific Olduvai domains and NOTCH2NL genes in human brain evolution. Hum Genet 138(7):715\u2013721","journal-title":"Hum Genet"},{"key":"2616_CR6","doi-asserted-by":"crossref","unstructured":"Florio M, et al. (2018) Evolution and cell-type specificity of human-specific genes preferentially expressed in progenitors of fetal neocortex. Elife 7","DOI":"10.7554\/eLife.32332"},{"issue":"8","key":"2616_CR7","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1038\/s41588-019-0459-y","volume":"51","author":"J Sone","year":"2019","unstructured":"Sone J et al (2019) Long-read sequencing identifies GGC repeat expansions in NOTCH2NLC associated with neuronal intranuclear inclusion disease. Nat Genet 51(8):1215\u20131221","journal-title":"Nat Genet"},{"key":"2616_CR8","doi-asserted-by":"crossref","unstructured":"Deng J et al (2021) Genetic origin of sporadic cases and RNA toxicity in neuronal intranuclear inclusion disease. J Med Genet","DOI":"10.1136\/jmedgenet-2020-107649"},{"issue":"11","key":"2616_CR9","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1016\/j.neuron.2021.03.038","volume":"109","author":"M Boivin","year":"2021","unstructured":"Boivin M et al (2021) Translation of GGC repeat expansions into a toxic polyglycine protein in NIID defines a novel class of human genetic disorders: the polyG diseases. Neuron 109(11):1825\u20131835.e5","journal-title":"Neuron"},{"issue":"9","key":"2616_CR10","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1002\/acn3.51151","volume":"7","author":"Z Chen","year":"2020","unstructured":"Chen Z et al (2020) Neuronal intranuclear inclusion disease is genetically heterogeneous. Ann Clin Transl Neurol 7(9):1716\u20131725","journal-title":"Ann Clin Transl Neurol"},{"issue":"7","key":"2616_CR11","doi-asserted-by":"publisher","first-page":"e57","DOI":"10.1093\/brain\/awaa144","volume":"143","author":"WY Yau","year":"2020","unstructured":"Yau WY et al (2020) GGC repeat expansion in NOTCH2NLC is rare in European patients with essential tremor. Brain 143(7):e57","journal-title":"Brain"},{"issue":"11","key":"2616_CR12","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1167\/iovs.61.11.27","volume":"61","author":"N Nakamura","year":"2020","unstructured":"Nakamura N et al (2020) Clinical characteristics of neuronal intranuclear inclusion disease-related retinopathy with CGG repeat expansions in the NOTCH2NLC gene. Invest Ophthalmol Vis Sci 61(11):27","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"12","key":"2616_CR13","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1001\/jamaneurol.2020.3023","volume":"77","author":"D Ma","year":"2020","unstructured":"Ma D et al (2020) Association of NOTCH2NLC Repeat Expansions With Parkinson disease. JAMA Neurol 77(12):1559\u20131563","journal-title":"JAMA Neurol"},{"issue":"24","key":"2616_CR14","doi-asserted-by":"publisher","first-page":"e3394","DOI":"10.1212\/WNL.0000000000010945","volume":"95","author":"Y Yuan","year":"2020","unstructured":"Yuan Y et al (2020) Identification of GGC repeat expansion in the NOTCH2NLC gene in amyotrophic lateral sclerosis. Neurology 95(24):e3394\u2013e3405","journal-title":"Neurology"},{"issue":"3","key":"2616_CR15","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1111\/cge.13802","volume":"98","author":"Z Chen","year":"2020","unstructured":"Chen Z et al (2020) Phenotypic bases of NOTCH2NLC GGC expansion positive neuronal intranuclear inclusion disease in a Southeast Asian cohort. Clin Genet 98(3):274\u2013281","journal-title":"Clin Genet"},{"issue":"1","key":"2616_CR16","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1093\/brain\/awz372","volume":"143","author":"QY Sun","year":"2020","unstructured":"Sun QY et al (2020) Expansion of GGC repeat in the human-specific NOTCH2NLC gene is associated with essential tremor. Brain 143(1):222\u2013233","journal-title":"Brain"},{"issue":"1","key":"2616_CR17","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.ajhg.2019.05.013","volume":"105","author":"Y Tian","year":"2019","unstructured":"Tian Y et al (2019) Expansion of human-specific GGC repeat in neuronal intranuclear inclusion disease-related disorders. Am J Hum Genet 105(1):166\u2013176","journal-title":"Am J Hum Genet"},{"key":"2616_CR18","doi-asserted-by":"publisher","first-page":"142.e1","DOI":"10.1016\/j.neurobiolaging.2020.01.010","volume":"89","author":"B Jiao","year":"2020","unstructured":"Jiao B et al (2020) Identification of expanded repeats in NOTCH2NLC in neurodegenerative dementias. Neurobiol Aging 89:142.e1\u2013142.e7","journal-title":"Neurobiol Aging"},{"issue":"3","key":"2616_CR19","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1002\/ana.26003","volume":"89","author":"WY Yau","year":"2021","unstructured":"Yau WY et al (2021) NOTCH2NLC intermediate-length repeat expansion and Parkinson\u2019s disease in patients of European descent. Ann Neurol 89(3):633\u2013635","journal-title":"Ann Neurol"},{"issue":"1","key":"2616_CR20","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1002\/ana.25925","volume":"89","author":"CH Shi","year":"2021","unstructured":"Shi CH et al (2021) NOTCH2NLC intermediate-length repeat expansions are associated with Parkinson disease. Ann Neurol 89(1):182\u2013187","journal-title":"Ann Neurol"},{"key":"2616_CR21","doi-asserted-by":"publisher","first-page":"102257","DOI":"10.1016\/j.scr.2021.102257","volume":"52","author":"Y Fan","year":"2021","unstructured":"Fan Y et al (2021) Generation of an induced pluripotent stem cell line (ZZUi020-A) from a patient with Parkinson\u2019s disease harboring the intermediate-length GGC repeat expansions in the NOTCH2NLC gene. Stem Cell Res 52:102257","journal-title":"Stem Cell Res"},{"issue":"Pt 12","key":"2616_CR22","doi-asserted-by":"publisher","first-page":"3170","DOI":"10.1093\/brain\/aww249","volume":"139","author":"J Sone","year":"2016","unstructured":"Sone J et al (2016) Clinicopathological features of adult-onset neuronal intranuclear inclusion disease. Brain 139(Pt 12):3170\u20133186","journal-title":"Brain"},{"key":"2616_CR23","doi-asserted-by":"crossref","unstructured":"Jih KY, et al. (2021) Analysis of NOTCH2NLC GGC repeat expansion in Taiwanese patients with amyotrophic lateral sclerosis. Neurobiol Aging","DOI":"10.1016\/j.neurobiolaging.2021.07.011"},{"issue":"1","key":"2616_CR24","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1186\/s40478-020-01084-4","volume":"8","author":"M Ogasawara","year":"2020","unstructured":"Ogasawara M et al (2020) CGG expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy with neurological manifestations. Acta Neuropathol Commun 8(1):204","journal-title":"Acta Neuropathol Commun"},{"issue":"6","key":"2616_CR25","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1093\/brain\/awab077","volume":"144","author":"J Yu","year":"2021","unstructured":"Yu J et al (2021) The GGC repeat expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy type 3. Brain 144(6):1819\u20131832","journal-title":"Brain"},{"issue":"6","key":"2616_CR26","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1002\/acn3.51371","volume":"8","author":"J Yu","year":"2021","unstructured":"Yu J et al (2021) GGC repeat expansions in NOTCH2NLC causing a phenotype of distal motor neuropathy and myopathy. Ann Clin Transl Neurol 8(6):1330\u20131342","journal-title":"Ann Clin Transl Neurol"},{"issue":"6","key":"2616_CR27","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1002\/ana.25586","volume":"86","author":"M Okubo","year":"2019","unstructured":"Okubo M et al (2019) GGC Repeat expansion of NOTCH2NLC in adult patients with leukoencephalopathy. Ann Neurol 86(6):962\u2013968","journal-title":"Ann Neurol"},{"issue":"3","key":"2616_CR28","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1002\/ana.25818","volume":"88","author":"WY Yau","year":"2020","unstructured":"Yau WY et al (2020) GGC Repeat expansion in NOTCH2NLC is rare in european leukoencephalopathy. Ann Neurol 88(3):641\u2013642","journal-title":"Ann Neurol"},{"issue":"7","key":"2616_CR29","doi-asserted-by":"publisher","first-page":"e56","DOI":"10.1093\/brain\/awaa142","volume":"143","author":"H Chen","year":"2020","unstructured":"Chen H et al (2020) Essential tremor as the early symptom of NOTCH2NLC gene-related repeat expansion disorder. Brain 143(7):e56","journal-title":"Brain"},{"issue":"3","key":"2616_CR30","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1002\/ana.25803","volume":"88","author":"ASL Ng","year":"2020","unstructured":"Ng ASL et al (2020) NOTCH2NLC GGC repeat expansions are associated with sporadic essential tremor: variable disease expressivity on long-term follow-up. Ann Neurol 88(3):614\u2013618","journal-title":"Ann Neurol"},{"issue":"1","key":"2616_CR31","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1093\/brain\/awaa348","volume":"144","author":"Y Yan","year":"2021","unstructured":"Yan Y et al (2021) Assessing the NOTCH2NLC GGC expansion in essential tremor patients from eastern China. Brain 144(1):e1","journal-title":"Brain"},{"issue":"11","key":"2616_CR32","doi-asserted-by":"publisher","first-page":"e89","DOI":"10.1093\/brain\/awaa291","volume":"143","author":"C Liao","year":"2020","unstructured":"Liao C et al (2020) Assessing the NOTCH2NLC GGC expansion in European patients with essential tremor. Brain 143(11):e89","journal-title":"Brain"},{"key":"2616_CR33","doi-asserted-by":"crossref","unstructured":"Jim\u00e9nez-Jim\u00e9nez FJ, et al. (2021) Genomic markers for essential tremor. Pharmaceuticals (Basel), 14(6)","DOI":"10.3390\/ph14060516"},{"issue":"4","key":"2616_CR34","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1002\/acn3.51021","volume":"7","author":"P Fang","year":"2020","unstructured":"Fang P et al (2020) Repeat expansion scanning of the NOTCH2NLC gene in patients with multiple system atrophy. Ann Clin Transl Neurol 7(4):517\u2013526","journal-title":"Ann Clin Transl Neurol"},{"issue":"11","key":"2616_CR35","doi-asserted-by":"publisher","first-page":"3187","DOI":"10.1007\/s00415-020-09945-7","volume":"267","author":"H Liang","year":"2020","unstructured":"Liang H et al (2020) Clinical and pathological features in adult-onset NIID patients with cortical enhancement. J Neurol 267(11):3187\u20133198","journal-title":"J Neurol"},{"issue":"1","key":"2616_CR36","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1080\/13816810.2020.1723119","volume":"41","author":"T Hayashi","year":"2020","unstructured":"Hayashi T et al (2020) Heterozygous GGC repeat expansion of NOTCH2NLC in a patient with neuronal intranuclear inclusion disease and progressive retinal dystrophy. Ophthalmic Genet 41(1):93\u201395","journal-title":"Ophthalmic Genet"},{"issue":"8","key":"2616_CR37","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1038\/s41588-019-0458-z","volume":"51","author":"H Ishiura","year":"2019","unstructured":"Ishiura H et al (2019) Noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and an overlapping disease. Nat Genet 51(8):1222\u20131232","journal-title":"Nat Genet"},{"issue":"1","key":"2616_CR38","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/s12883-020-01712-5","volume":"20","author":"M Li","year":"2020","unstructured":"Li M et al (2020) Multiple reversible encephalitic attacks: a rare manifestation of neuronal intranuclear inclusion disease. BMC Neurol 20(1):125","journal-title":"BMC Neurol"},{"issue":"8","key":"2616_CR39","doi-asserted-by":"publisher","first-page":"e69","DOI":"10.1093\/brain\/awaa210","volume":"143","author":"ASL Ng","year":"2020","unstructured":"Ng ASL et al (2020) NOTCH2NLC-linked neuronal intranuclear inclusion body disease and fragile X-associated tremor\/ataxia syndrome. Brain 143(8):e69","journal-title":"Brain"},{"key":"2616_CR40","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.parkreldis.2020.03.025","volume":"74","author":"SY Lim","year":"2020","unstructured":"Lim SY et al (2020) Adult-onset neuronal intranuclear inclusion disease mimicking Fragile X-associated tremor-ataxia syndrome in ethnic Chinese patients. Parkinsonism Relat Disord 74:25\u201327","journal-title":"Parkinsonism Relat Disord"},{"issue":"5","key":"2616_CR41","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1007\/s10072-019-04195-6","volume":"41","author":"HK Raza","year":"2020","unstructured":"Raza HK et al (2020) Recent progress in neuronal intranuclear inclusion disease: a review of the literature. Neurol Sci 41(5):1019\u20131025","journal-title":"Neurol Sci"},{"issue":"10","key":"2616_CR42","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1002\/acn3.51189","volume":"7","author":"H Chen","year":"2020","unstructured":"Chen H et al (2020) Re-defining the clinicopathological spectrum of neuronal intranuclear inclusion disease. Ann Clin Transl Neurol 7(10):1930\u20131941","journal-title":"Ann Clin Transl Neurol"},{"key":"2616_CR43","doi-asserted-by":"crossref","unstructured":"Zhang GJ, et al. (2021) Clinicopathological features of neuronal intranuclear inclusion disease diagnosed by skin biopsy. Neurol Sci","DOI":"10.1007\/s10072-021-05526-2"},{"key":"2616_CR44","doi-asserted-by":"publisher","first-page":"624321","DOI":"10.3389\/fneur.2021.624321","volume":"12","author":"J Pang","year":"2021","unstructured":"Pang J et al (2021) The value of NOTCH2NLC gene detection and skin biopsy in the diagnosis of neuronal intranuclear inclusion disease. Front Neurol 12:624321","journal-title":"Front Neurol"},{"issue":"8","key":"2616_CR45","doi-asserted-by":"publisher","first-page":"e51","DOI":"10.1093\/brain\/awx156","volume":"140","author":"E Gelpi","year":"2017","unstructured":"Gelpi E et al (2017) Neuronal intranuclear (hyaline) inclusion disease and fragile X-associated tremor\/ataxia syndrome: a morphological and molecular dilemma. Brain 140(8):e51","journal-title":"Brain"},{"key":"2616_CR46","doi-asserted-by":"publisher","first-page":"655568","DOI":"10.3389\/fncel.2021.655568","volume":"15","author":"K Xu","year":"2021","unstructured":"Xu K et al (2021) Therapeutic development for CGG repeat expansion-associated neurodegeneration. Front Cell Neurosci 15:655568","journal-title":"Front Cell Neurosci"},{"key":"2616_CR47","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.gde.2020.05.029","volume":"65","author":"H Ishiura","year":"2020","unstructured":"Ishiura H, Tsuji S (2020) Advances in repeat expansion diseases and a new concept of repeat motif-phenotype correlation. Curr Opin Genet Dev 65:176\u2013185","journal-title":"Curr Opin Genet Dev"},{"issue":"11","key":"2616_CR48","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1016\/j.neuron.2021.05.018","volume":"109","author":"ME Ehrlich","year":"2021","unstructured":"Ehrlich ME, Ellerby LM (2021) Neuronal intranuclear inclusion disease: polyglycine protein is the culprit. Neuron 109(11):1757\u20131760","journal-title":"Neuron"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-021-02616-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-021-02616-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-021-02616-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T08:51:48Z","timestamp":1675846308000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-021-02616-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,31]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["2616"],"URL":"https:\/\/doi.org\/10.1007\/s12035-021-02616-2","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,31]]},"assertion":[{"value":"11 September 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval and Consent to Participate"}},{"value":"All authors agreed to publish the contents.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}