{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:14:11Z","timestamp":1791519251288,"version":"4.3.4"},"reference-count":17,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/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\/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":["JP18H02742"],"award-info":[{"award-number":["JP18H02742"]}],"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":["JP20K16604"],"award-info":[{"award-number":["JP20K16604"]}],"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":["JP21H02842"],"award-info":[{"award-number":["JP21H02842"]}],"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":["JP21K15702"],"award-info":[{"award-number":["JP21K15702"]}],"id":[{"id":"10.13039\/501100001691","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"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Biallelic <jats:italic>POLR3B<\/jats:italic> mutations cause a rare hypomyelinating leukodystrophy. De novo <jats:italic>POLR3B<\/jats:italic> heterozygous mutations were recently associated with afferent ataxia, spasticity, variable intellectual disability, and epilepsy, and predominantly demyelinating sensorimotor peripheral neuropathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed whole\u2010exome sequencing (WES) of DNA samples from 804 Charcot\u2013Marie\u2013Tooth (CMT) cases that could not be genetically diagnosed by DNA\u2010targeted resequencing microarray using next\u2010generation sequencers. Using WES data, we analyzed the <jats:italic>POLR3B<\/jats:italic> mutations and confirmed their clinical features.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified de novo <jats:italic>POLR3B<\/jats:italic> heterozygous missense mutations in two patients. These patients presented with early\u2010onset demyelinating sensorimotor neuropathy without ataxia, spasticity, or cognitive impairment. Patient 1 showed mild cerebellar atrophy and spinal cord atrophy on magnetic resonance imaging and eventually died of respiratory failure in her 50s. We classified these mutations as pathogenic based on segregation studies, comparison with control database, and in silico analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study is the third report on patients with demyelinating CMT harboring heterozygous <jats:italic>POLR3B<\/jats:italic> mutations and verifies the pathogenicity of <jats:italic>POLR3B<\/jats:italic> mutations in CMT. Although extremely rare in our large Japanese case series, <jats:italic>POLR3B<\/jats:italic> mutations should be added to the CMT\u2010related gene panel for comprehensive genetic screening, particularly for patients with early\u2010onset demyelinating CMT.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51555","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T14:57:44Z","timestamp":1651157864000},"page":"747-755","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Novel de novo <scp><i>POLR3B<\/i><\/scp> mutations responsible for demyelinating Charcot\u2013Marie\u2013Tooth disease in Japan"],"prefix":"10.1002","volume":"9","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":"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3808-7813","authenticated-orcid":false,"given":"Jun\u2010Hui","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":"Akiko","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima 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