{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:47:26Z","timestamp":1789040846267,"version":"build-2803163510"},"reference-count":21,"publisher":"BMJ","issue":"8","funder":[{"name":"Ministry of Health, Labour and Welfare, Japan","award":["201610002B"],"award-info":[{"award-number":["201610002B"]}]},{"name":"Ministry of Health, Labour and Welfare, Japan","award":["JMPH19189624"],"award-info":[{"award-number":["JMPH19189624"]}]},{"name":"Ministry of Health, Labour and Welfare, Japan","award":["JMPH21445246"],"award-info":[{"award-number":["JMPH21445246"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["17929553"],"award-info":[{"award-number":["17929553"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["201442014A"],"award-info":[{"award-number":["201442014A"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["201442071A"],"award-info":[{"award-number":["201442071A"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JSPS","award":["15K09312"],"award-info":[{"award-number":["15K09312"]}]},{"name":"JSPS","award":["19H03577"],"award-info":[{"award-number":["19H03577"]}]},{"name":"JSPS","award":["JP18H02742"],"award-info":[{"award-number":["JP18H02742"]}]},{"name":"JSPS","award":["JP20K16604"],"award-info":[{"award-number":["JP20K16604"]}]},{"name":"JSPS","award":["JP21H02842"],"award-info":[{"award-number":["JP21H02842"]}]},{"name":"JSPS","award":["JP21K15702"],"award-info":[{"award-number":["JP21K15702"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"accepted":{"date-parts":[[2023,3,7]]},"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>\n<jats:italic>NOTCH2NLC<\/jats:italic>\nGGC repeat expansions have been associated with various neurogenerative disorders, including neuronal intranuclear inclusion disease and inherited peripheral neuropathies (IPNs). However, only a few\n<jats:italic>NOTCH2NLC<\/jats:italic>\n-related disease studies in IPN have been reported, and the clinical and genetic spectra remain unclear. Thus, this study aimed to describe the clinical and genetic manifestations of\n<jats:italic>NOTCH2NLC<\/jats:italic>\n-related IPNs.\n<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Method<\/jats:title>\n<jats:p>\nAmong 2692 Japanese patients clinically diagnosed with IPN\/Charcot\u2013Marie\u2013Tooth disease (CMT), we analysed\n<jats:italic>NOTCH2NLC<\/jats:italic>\nrepeat expansion in 1783 unrelated patients without a genetic diagnosis. Screening and repeat size determination of\n<jats:italic>NOTCH2NLC<\/jats:italic>\nrepeat expansion were performed using repeat-primed PCR and fluorescence amplicon length analysis-PCR.\n<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>\n<jats:italic>NOTCH2NLC<\/jats:italic>\nrepeat expansions were identified in 26 cases of IPN\/CMT from 22 unrelated families. The mean median motor nerve conduction velocity was 41 m\/s (range, 30.8\u201359.4), and 18 cases (69%) were classified as intermediate CMT. The mean age of onset was 32.7 (range, 7\u201361) years. In addition to motor sensory neuropathy symptoms, dysautonomia and involuntary movements were common (44% and 29%). Furthermore, the correlation between the age of onset or clinical symptoms and the repeat size remains unclear.\n<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>\nThese findings of this study help us understand the clinical heterogeneity of\n<jats:italic>NOTCH2NLC<\/jats:italic>\n-related disease, such as non-length-dependent motor dominant phenotype and prominent autonomic involvement. This study also emphasise the importance of genetic screening, regardless of the age of onset and type of CMT, particularly in patients of Asian origin, presenting with intermediate conduction velocities and dysautonomia.\n<\/jats:p>\n<\/jats:sec>","DOI":"10.1136\/jnnp-2022-330769","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T17:20:49Z","timestamp":1679505649000},"page":"622-630","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Clinical phenotypic diversity of\n<i>NOTCH2NLC<\/i>\n-related disease in the largest case series of inherited peripheral neuropathy in Japan"],"prefix":"10.1136","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6187-9042","authenticated-orcid":false,"given":"Masahiro","family":"Ando","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiro","family":"Higuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3808-7813","authenticated-orcid":false,"given":"Jun-Hui","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Yoshimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Dozono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Hobara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumikazu","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Noguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Takeuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Takei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Hiramatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4909-7769","authenticated-orcid":false,"given":"Satoshi","family":"Nozuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonori","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Sakiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Hashiguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8215-8853","authenticated-orcid":false,"given":"Eiji","family":"Matsuura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Sone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Takashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,3,22]]},"reference":[{"key":"2025021202350592000_94.8.622.1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2010.03037.x"},{"key":"2025021202350592000_94.8.622.2","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.neurol.2016.06.007","article-title":"Hereditary 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