{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:21:34Z","timestamp":1790511694819,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T00:00:00Z","timestamp":1501718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["2646125"],"award-info":[{"award-number":["2646125"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["22129001"],"award-info":[{"award-number":["22129001"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["22129002"],"award-info":[{"award-number":["22129002"]}],"id":[{"id":"10.13039\/501100000646","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":[[2017,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background and purpose<\/jats:title>\n                    <jats:p>\n                      The microrchidia family\n                      <jats:styled-content style=\"fixed-case\">CW<\/jats:styled-content>\n                      \u2010type zinc finger 2 gene (\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">MORC<\/jats:styled-content>\n                        2\n                      <\/jats:italic>\n                      ) was newly identified as a causative gene of Charcot\u2013Marie\u2013Tooth disease (\n                      <jats:styled-content style=\"fixed-case\">CMT<\/jats:styled-content>\n                      ) type 2Z in 2016. We aimed to describe the clinical and mutational spectrum of patients with\n                      <jats:styled-content style=\"fixed-case\">CMT<\/jats:styled-content>\n                      harboring\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">MORC<\/jats:styled-content>\n                        2\n                      <\/jats:italic>\n                      mutations in Japan.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed samples from 781 unrelated patients clinically diagnosed with\n                      <jats:styled-content style=\"fixed-case\">CMT<\/jats:styled-content>\n                      using deoxyribonucleic acid microarray or targeted resequencing by next\u2010generation sequencing, and samples from 434 mutation\u2010negative patients were subjected to whole\u2010exome sequencing. We extracted\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">MORC<\/jats:styled-content>\n                        2\n                      <\/jats:italic>\n                      variants from these whole\u2010exome sequencing data and classified them according to American College of Medical Genetics standards and guidelines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">MORC<\/jats:styled-content>\n                        2\n                      <\/jats:italic>\n                      variants in 13 patients. As the second most common causative gene of\n                      <jats:styled-content style=\"fixed-case\">CMT type<\/jats:styled-content>\n                      2 after\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">MFN<\/jats:styled-content>\n                      <\/jats:italic>\n                      2,\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">MORC<\/jats:styled-content>\n                        2\n                      <\/jats:italic>\n                      variants were detected in 2.7% of patients with\n                      <jats:styled-content style=\"fixed-case\">CMT type<\/jats:styled-content>\n                      2. The mean age of onset was 10.3\u00a0\u00b1\u00a08.7\u00a0years, and the inheritance pattern was mostly sporadic (11\/13 patients, 84.6%). The clinical phenotype was typically length\u2010dependent polyneuropathy, and electrophysiological studies revealed sensory\u2010dominant axonal neuropathy. Mental retardation was identified in 4\/13 patients (30.8%). p.Arg190Trp, as a mutational hotspot, was observed in eight unrelated families. We also identified two novel probably pathogenic variants, p.Cys345Tyr and p.Ala369Val, and one novel uncertain significance variant, p.Tyr332Cys.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study is the largest report of patients harboring\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">MORC<\/jats:styled-content>\n                        2\n                      <\/jats:italic>\n                      variants. We revealed a clinical and mutational spectrum of Japanese patients with\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">MORC<\/jats:styled-content>\n                        2\n                      <\/jats:italic>\n                      variants. More attention should be paid to cognitive impairment, and the responsible mechanism requires further research for elucidation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.13360","type":"journal-article","created":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T16:24:43Z","timestamp":1501777483000},"page":"1274-1282","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Clinical and mutational spectrum of Charcot\u2013Marie\u2013Tooth disease type 2Z caused by\n                    <i>MORC2<\/i>\n                    variants in Japan"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6187-9042","authenticated-orcid":false,"given":"M.","family":"Ando","sequence":"first","affiliation":[{"name":"Department of Neurology and Geriatrics Graduate School of Medical and Dental Sciences, Kagoshima University Kagoshima"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Graduate School of Medical and Dental Sciences, Kagoshima University Kagoshima"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Graduate School of Medical and Dental Sciences, Kagoshima University Kagoshima"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.\u2010H.","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Graduate School of Medical and Dental Sciences, Kagoshima University Kagoshima"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Hiramatsu","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Graduate School of Medical and Dental Sciences, Kagoshima University Kagoshima"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Higuchi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Graduate School of Medical and Dental Sciences, Kagoshima University Kagoshima"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Hashiguchi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Graduate School of Medical and Dental Sciences, Kagoshima University Kagoshima"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Mitsui","sequence":"additional","affiliation":[{"name":"Department of Neurology Graduate School of Medicine The University of Tokyo Tokyo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Ishiura","sequence":"additional","affiliation":[{"name":"Department of Neurology Graduate School of Medicine The University of Tokyo 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