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Adv."],"published-print":{"date-parts":[[2026,7,17]]},"abstract":"<jats:p>\n                    Primary idiopathic hyperhidrosis (PIH) is a poorly understood disorder characterized by excessive sweating. We identify a genetically defined subset of PIH associated with rare coding changes in voltage-gated Na\n                    <jats:sup>+<\/jats:sup>\n                    (Na\n                    <jats:sub>V<\/jats:sub>\n                    ) channels. Whole-exome sequencing of hereditary PIH families revealed gene-level enrichment within the Na\n                    <jats:sub>V<\/jats:sub>\n                    channel family, with\n                    <jats:italic toggle=\"yes\">SCN10A<\/jats:italic>\n                    (Na\n                    <jats:sub>V<\/jats:sub>\n                    1.8) most strongly implicated. A knock-in mouse carrying the clinically observed Na\n                    <jats:sub>V<\/jats:sub>\n                    1.8\n                    <jats:sup>p.R14L<\/jats:sup>\n                    substitution recapitulated excessive sweating. Na\n                    <jats:sub>V<\/jats:sub>\n                    1.8 was detected in a subset of postganglionic neurons in thoracic sympathetic ganglia in humans and mice, where p.R14L produced a gain-of-function profile that enhanced cholinergic responsiveness. Excessive sweating in mutant mice was reversible with Na\n                    <jats:sub>V<\/jats:sub>\n                    channel inhibition, including clinically used agents and a Na\n                    <jats:sub>V<\/jats:sub>\n                    1.8-preferential compound. Together, these findings define a targetable neurocutaneous channelopathy underlying a subset of PIH and support a model in which excessive sweating arises from either gland-intrinsic dysfunction or altered sympathetic drive, motivating stratified therapeutic approaches.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aed3221","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:58:48Z","timestamp":1784311128000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["A neurocutaneous Na\n                    <sub>V<\/sub>\n                    1.8 channelopathy underlies a genetic subtype of primary idiopathic hyperhidrosis"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5418-7112","authenticated-orcid":true,"given":"Suguru","family":"Yamauchi","sequence":"first","affiliation":[{"name":"Department of Surgery, The Sidney Kimmel Cancer Center, 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