{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T01:06:20Z","timestamp":1779930380377,"version":"3.53.1"},"reference-count":18,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"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":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Recessive mutations in <jats:italic>SLC12A6<\/jats:italic> have been linked to hereditary motor sensory neuropathy with agenesis of the corpus callosum. Patients with early\u2010onset peripheral neuropathy associated with <jats:italic>SLC12A6<\/jats:italic> heterozygous variants were reported in 2016. Only five families and three variants have been reported to date, and the spectrum is unclear. Here, we aim to describe the clinical and mutation spectra of <jats:italic>SLC12A6<\/jats:italic>\u2010related Charcot\u2013Marie\u2013Tooth (CMT) disease in Japanese patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We extracted <jats:italic>SLC12A6<\/jats:italic> variants from our DNA microarray and targeted resequencing data obtained from 2598 patients with clinically suspected CMT who were referred to our genetic laboratory by neurological or neuropediatric departments across Japan. And we summarized the clinical and genetic features of these patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In seven unrelated families, we identified one previously reported and three novel likely pathogenic <jats:italic>SLC12A6<\/jats:italic> heterozygous variants, as well as two variants of uncertain significance. The mean age of onset for these patients was 17.5\u2009\u00b1\u200916.1\u2009years. Regarding electrophysiology, the median motor nerve conduction velocity was 39.6\u2009\u00b1\u20099.5\u2009m\/sec. For the first time, we observed intellectual disability in three patients. One patient developed epilepsy, and her brain MRI revealed frontal and temporal lobe atrophy without changes in white matter and corpus callosum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Screening for the <jats:italic>SLC12A6<\/jats:italic> gene should be considered in patients with CMT, particularly those with central nervous system lesions, such as cognitive impairment and epilepsy, regardless of the CMT subtype.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51603","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T05:51:46Z","timestamp":1655963506000},"page":"902-911","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Novel heterozygous variants of <scp><i>SLC12A6<\/i><\/scp> in Japanese families with <scp>Charcot\u2013Marie\u2013Tooth<\/scp> disease"],"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"}]},{"given":"Junhui","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics Kagoshima University Graduate School of Medical and Dental Sciences  Kagoshima 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