{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:50:00Z","timestamp":1787637000117,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,8,3]],"date-time":"2018-08-03T00:00:00Z","timestamp":1533254400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["201331010B"],"award-info":[{"award-number":["201331010B"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["201610002B"],"award-info":[{"award-number":["201610002B"]}],"id":[{"id":"10.13039\/501100003478","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"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["26461275"],"award-info":[{"award-number":["26461275"]}],"id":[{"id":"10.13039\/501100001691","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":[[2018,12]]},"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>X\u2010linked Charcot\u2013Marie\u2013Tooth disease type 1 (<jats:styled-content style=\"fixed-case\">CMTX<\/jats:styled-content>1), caused by mutations in gap junction protein beta 1 (<jats:styled-content style=\"fixed-case\">GJB<\/jats:styled-content>1), is characterized by various central nervous system symptoms and gender differences of clinical severity. The aim of this study was to identify the frequency and mutation spectrum of <jats:styled-content style=\"fixed-case\">CMTX<\/jats:styled-content>1 patients in Japan and to demonstrate their phenotypic diversities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using three high\u2010throughput sequencing systems, targeted gene panel sequencing on 1483 unrelated index patients with suspected Charcot\u2013Marie\u2013Tooth (<jats:styled-content style=\"fixed-case\">CMT<\/jats:styled-content>) disease was performed. The peripheral and central nervous system involvements of all patients with <jats:italic><jats:styled-content style=\"fixed-case\">GJB<\/jats:styled-content>1<\/jats:italic> variants were assessed retrospectively and a detailed gender comparison was conducted with the <jats:styled-content style=\"fixed-case\">CMT<\/jats:styled-content> examination score.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010three novel and 36 described <jats:italic><jats:styled-content style=\"fixed-case\">GJB<\/jats:styled-content>1<\/jats:italic> variants were identified from 88 pedigrees, in which 34 female and 78 male patients were enrolled. Mean age at onset of the male patients was much younger than the females, 21.56 \u00b1 17.63 years vs. 35.53 \u00b1 23.72 years (<jats:italic>P<\/jats:italic> = 0.007). Male patients presented with more severe phenotypes in every examination item, but statistical differences were observed only in motor dysfunctions of the lower extremities and vibration sensation. No significant sensory difference was identified between genders, either clinically or electrophysiologically. Central nervous system dysfunctions were found in 15 patients from 12 pedigrees. Therein, six patients developed stroke\u2010like phenotypes, with dysarthria as the leading symptom.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A relatively lower frequency of <jats:styled-content style=\"fixed-case\">CMTX<\/jats:styled-content>1 (5.9%) was demonstrated and a broad mutation spectrum of <jats:italic><jats:styled-content style=\"fixed-case\">GJB<\/jats:styled-content>1<\/jats:italic> was described. Detailed clinical differences between genders and various central nervous system symptoms were also illustrated, even in the same pedigree.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.13750","type":"journal-article","created":{"date-parts":[[2018,7,12]],"date-time":"2018-07-12T05:50:10Z","timestamp":1531374610000},"page":"1454-1461","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Genetic and phenotypic profile of 112 patients with X\u2010linked Charcot\u2013Marie\u2013Tooth disease type 1"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3808-7813","authenticated-orcid":false,"given":"J.\u2010H.","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Neurology and Geriatrics Graduate School of Medical and Dental Sciences Kagoshima University Kagoshima 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