{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T02:53:01Z","timestamp":1787539981719,"version":"build-2736575974"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,7,30]],"date-time":"2017-07-30T00:00:00Z","timestamp":1501372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"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\/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"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22129001"],"award-info":[{"award-number":["22129001"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22129002"],"award-info":[{"award-number":["22129002"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Charcot\u2010Marie\u2010Tooth disease (CMT) constitutes a heterogeneous group affecting motor and sensory neurons in the peripheral nervous system. <jats:italic>MFN2<\/jats:italic> mutations are the most common cause of axonal CMT. We describe the clinical and mutational spectra of CMT patients harboring <jats:italic>MFN2<\/jats:italic> mutations in Japan. We analyzed 1,334 unrelated patients with clinically suspected CMT referred by neurological and neuropediatric departments throughout Japan. We conducted mutation screening using a DNA microarray, targeted resequencing, and whole\u2010exome sequencing. We identified pathogenic or likely pathogenic <jats:italic>MFN2<\/jats:italic> variants from 79 CMT patients, comprising 44 heterozygous and 1 compound heterozygous variants. A total of 15 novel variants were detected. An autosomal dominant family history was determined in 43 cases, and the remaining 36 cases were reported as sporadic with no family history. The mean onset age of CMT in these patients was 12\u2009\u00b1\u200914 (range 0\u201359) years. We observed neuropathic symptoms in all patients. Some had optic atrophy, vocal cord paralysis, or spasticity. We detected a compound heterozygous <jats:italic>MFN2<\/jats:italic> mutation in a patient with a severe phenotype and the co\u2010occurrence of <jats:italic>MFN2<\/jats:italic> and <jats:italic>PMP22<\/jats:italic> mutations in a patient with an uncommon phenotype. <jats:italic>MFN2<\/jats:italic> is the most frequent causative gene of CMT2 in Japan. We present 15 novel variants and broad clinical and mutational spectra of Japanese <jats:italic>MFN2<\/jats:italic>\u2010related CMT patients. Regardless of the onset age and inheritance pattern, <jats:italic>MFN2<\/jats:italic> gene analysis should be performed. Combinations of causative genes should be considered to explain the phenotypic diversity.<\/jats:p>","DOI":"10.1111\/jns.12228","type":"journal-article","created":{"date-parts":[[2017,6,29]],"date-time":"2017-06-29T07:26:50Z","timestamp":1498721210000},"page":"191-199","source":"Crossref","is-referenced-by-count":36,"title":["Clinical and genetic diversities of Charcot\u2010Marie\u2010Tooth disease with <i>MFN2<\/i> mutations in a large case study"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6187-9042","authenticated-orcid":false,"given":"Masahiro","family":"Ando","sequence":"first","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Hashiguchi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1768-3181","authenticated-orcid":false,"given":"Akiko","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Hiramatsu","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3808-7813","authenticated-orcid":false,"given":"Junhui","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiro","family":"Higuchi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Mitsui","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2975-7309","authenticated-orcid":false,"given":"Hiroyuki","family":"Ishiura","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Umemura","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Aichi Prefectural Colony Central Hospital  Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Maruyama","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Aichi Prefectural Colony Central Hospital  Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Matsushige","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yamaguchi University Graduate School of Medicine  Yamaguchi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Morishita","sequence":"additional","affiliation":[{"name":"Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences The University of Tokyo  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Neurology, North Medical Center Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoji","family":"Tsuji","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Takashima","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and 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