{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T19:51:19Z","timestamp":1773431479123,"version":"3.50.1"},"reference-count":33,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/ S005021\/1"],"award-info":[{"award-number":["MR\/ S005021\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["U54NS065712"],"award-info":[{"award-number":["U54NS065712"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"accepted":{"date-parts":[[2025,8,25]]},"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Heterozygous variants in\n                      <jats:italic>SLC12A6<\/jats:italic>\n                      have recently been shown to cause dominant Charcot-Marie-Tooth disease (CMT). We aim to characterise the phenotype of patients with previously reported and novel heterozygous variants in the gene and understand any genotype-phenotype correlation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients were clinically and genetically assessed in sites from Europe, Australia, Brazil and the USA. All patients underwent whole exome or whole genome sequencing. Variants were classified using American College of Medical Genetics and Genomics criteria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty-three individuals from 13 families carried nine variants classified either as pathogenic\/likely pathogenic or variants of uncertain significance segregating in multiple family members, including five novel variants. Forty-eight percent (11\/23) were male with a mean age of disease onset of 15.7 years (range 1\u201345 years). Clinical phenotype varied dramatically with genotype; Arg207His and Ser647Pro caused a severe childhood-onset, sensory and motor, conduction-slowing neuropathy, whereas Gly552Asp caused a mild, adult-onset, sensory-predominant neuropathy, Thr991Ala an infantile-onset motor neuropathy, and the Met282Lys\/Gly286Cys locus a complex, axonal neuropathy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Heterozygous variants in\n                      <jats:italic>SLC12A6<\/jats:italic>\n                      can cause CMT of all clinical phenotypes, severity and age of onset, depending on the genotype. Such phenotypic diversity has not been described for any other CMT gene, and more work is needed to understand disease mechanisms to guide future therapeutic options.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jnnp-2025-336643","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T18:20:25Z","timestamp":1767810025000},"page":"283-292","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Spectrum of dominant Charcot-Marie-Tooth disease due to\n                    <i>SLC12A6<\/i>\n                    variants"],"prefix":"10.1136","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9802-2683","authenticated-orcid":false,"given":"Christopher J","family":"Record","sequence":"first","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffany","family":"Grider","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Iowa Health Care Medical Center, Iowa City, Iowa, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana P","family":"Rebelo","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Laurini","sequence":"additional","affiliation":[{"name":"Neuromuscular Repair Unit, Institute of Experimental Neurology (InSpe), Division of Neuroscience, IRCCS Ospedale San Raffaele, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariola","family":"Skorupinska","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1568-5965","authenticated-orcid":false,"given":"Matt C","family":"Danzi","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roy","family":"Poh","sequence":"additional","affiliation":[{"name":"Neurogenetics Laboratory, North Thames Genomics Laboratory Hub, National Hospital for Neurology and Neurosurgery, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro J","family":"Tomaselli","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Sao Paulo Ribeirao Preto Medical School, Ribeirao Preto, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4325-3414","authenticated-orcid":false,"given":"Rodrigo S","family":"Frezatti","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Sao Paulo Ribeirao Preto Medical School, Ribeirao Preto, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Dominik","sequence":"additional","affiliation":[{"name":"Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca","family":"Grosz","sequence":"additional","affiliation":[{"name":"Northcott Neuroscience Laboratory, ANZAC Research Institute, Sydney Local Health District and Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melina","family":"Ellis","sequence":"additional","affiliation":[{"name":"Northcott Neuroscience Laboratory, ANZAC Research Institute, Sydney Local Health District and Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3482-6962","authenticated-orcid":false,"given":"Kishore R","family":"Kumar","sequence":"additional","affiliation":[{"name":"Molecular Medicine Laboratory and Neurology Department, Concord Repatriation General Hospital, Concord, New South Wales, Australia"},{"name":"Translational Neurogenomics Group, Genomic and Inherited Disease Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3395-1633","authenticated-orcid":false,"given":"Matthew B","family":"Harms","sequence":"additional","affiliation":[{"name":"Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3816-6124","authenticated-orcid":false,"given":"Conrad 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Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK"},{"name":"Department of Clinical Neurophysiology, Norfolk and Norwich University Hospital, Norwich, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James KL","family":"Holt","sequence":"additional","affiliation":[{"name":"Walton Centre for Neurology and Neurosurgery, Liverpool, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Astrid","family":"Weber","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Genomic Medicine, Liverpool Women\u2019s Hospital, Liverpool, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard T","family":"Dineen","sequence":"additional","affiliation":[{"name":"Department of 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