{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T09:03:55Z","timestamp":1784106235949,"version":"3.55.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R35NS105076"],"award-info":[{"award-number":["R35NS105076"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01AT011447"],"award-info":[{"award-number":["R01AT011447"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dr. Miriam and Sheldon G. Adelson Foundation"},{"name":"National Research Foundation Fellowship NRF","award":["2018R1A6A3A03012431"],"award-info":[{"award-number":["2018R1A6A3A03012431"]}]},{"name":"Nancy Taylor Foundation"},{"name":"U.S. Department of Veterans Affairs Rehabilitation Research and Development Service"},{"name":"Center for Neuroscience and Regeneration Research"},{"DOI":"10.13039\/100005326","name":"Yale University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Inherited erythromelalgia, small fibre neuropathy and paroxysmal extreme pain disorder are caused by gain-of-function mutations in the voltage-gated sodium channel Nav1.7. It remains unknown how different mutations in the same channel enhancing electrogenesis in sensory neurons results in such distinct disease presentations.<\/jats:p>\n                  <jats:p>Most of the work analysing the impact of these mutations on electrophysiological properties has used overexpression systems in cell lines and rodent sensory neurons, which might differ from the natural context. We have differentiated sensory neurons from induced pluripotent stem cells derived from patient samples that have the Nav1.7 A1632G mutation.<\/jats:p>\n                  <jats:p>This strategy reveals changes in electrophysiological properties, not previously observed in cell lines, that might be important for disease presentation. Furthermore, using CRISPR\/Cas9, we corrected this mutation, which reduced the underlying hyperexcitability, providing a path for personalized medicine to treat these disorders, and we introduced the mutation into control induced pluripotent stem cells, which generated hyperexcitability, providing causality.<\/jats:p>\n                  <jats:p>Induced pluripotent stem cell sensory neurons are a robust, scalable and relevant model to study the effects of gain-of-function mutations in ion channels in pain-related disorders.<\/jats:p>","DOI":"10.1093\/brain\/awaf155","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T06:49:57Z","timestamp":1745477397000},"page":"3718-3726","source":"Crossref","is-referenced-by-count":2,"title":["Correction of sodium channel mutations in sensory neurons reverses aberrant properties"],"prefix":"10.1093","volume":"148","author":[{"given":"Jaehoon","family":"Shim","sequence":"first","affiliation":[{"name":"F.M. Kirby Neurobiology Center, Boston Children\u2019s Hospital , Boston, MA 02115 ,","place":["USA"]},{"name":"Department of Neurobiology, Harvard Medical School , Boston, MA 02115 ,","place":["USA"]},{"name":"The Stem Cell and Regenerative Biology Department, Harvard University , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale University School of Medicine , New Haven, CT 06510 ,","place":["USA"]},{"name":"Center for Neuroscience and Regeneration Research, Yale University School of Medicine , New Haven, CT 06510 ,","place":["USA"]},{"name":"Center for Restoration of Function after Nervous System Injury, Veterans Affairs Medical Center , West Haven, CT 06516 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0363-6031","authenticated-orcid":false,"given":"Daniel G","family":"Taub","sequence":"additional","affiliation":[{"name":"F.M. Kirby Neurobiology Center, Boston Children\u2019s Hospital , Boston, MA 02115 ,","place":["USA"]},{"name":"Department of Neurobiology, Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata A","family":"Mis","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale University School of Medicine , New Haven, CT 06510 ,","place":["USA"]},{"name":"Center for Neuroscience and Regeneration Research, Yale University School of Medicine , New Haven, CT 06510 ,","place":["USA"]},{"name":"Center for Restoration of Function after Nervous System Injury, Veterans Affairs Medical Center , West Haven, CT 06516 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betsy R","family":"Schulman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale University School of Medicine , New Haven, CT 06510 ,","place":["USA"]},{"name":"Center for Neuroscience and Regeneration Research, Yale University School of Medicine , New Haven, CT 06510 ,","place":["USA"]},{"name":"Center for Restoration of Function after Nervous System Injury, Veterans Affairs Medical Center , West Haven, CT 06516 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Snavely","sequence":"additional","affiliation":[{"name":"F.M. Kirby Neurobiology Center, Boston Children\u2019s Hospital , Boston, MA 02115 ,","place":["USA"]},{"name":"Department of Neurobiology, Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Chih","family":"Cheng","sequence":"additional","affiliation":[{"name":"F.M. Kirby Neurobiology Center, Boston Children\u2019s Hospital , Boston, MA 02115 ,","place":["USA"]},{"name":"Department of Neurobiology, Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric","family":"Laedermann","sequence":"additional","affiliation":[{"name":"F.M. Kirby Neurobiology Center, Boston Children\u2019s Hospital , Boston, MA 02115 ,","place":["USA"]},{"name":"Department of Neurobiology, Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth D","family":"Buttermore","sequence":"additional","affiliation":[{"name":"F.M. Kirby Neurobiology Center, Boston Children\u2019s Hospital , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Ren","sequence":"additional","affiliation":[{"name":"F.M. Kirby Neurobiology Center, Boston Children\u2019s Hospital , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal","family":"Hermawan","sequence":"additional","affiliation":[{"name":"F.M. Kirby Neurobiology Center, Boston Children\u2019s Hospital , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Dou","sequence":"additional","affiliation":[{"name":"F.M. Kirby Neurobiology Center, Boston Children\u2019s Hospital , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2489-4825","authenticated-orcid":false,"given":"Riki","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Department of Neurology, David Geffen School of Medicine, University of California Los Angeles , Los Angeles, CA 90095 ,","place":["USA"]},{"name":"Semel Institute for Neuroscience and Human Behavior, University of California , Los Angeles, CA 90095 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2896-3450","authenticated-orcid":false,"given":"Daniel H","family":"Geschwind","sequence":"additional","affiliation":[{"name":"Department of Neurology, David Geffen School of Medicine, University of California Los Angeles , Los Angeles, CA 90095 ,","place":["USA"]},{"name":"Semel Institute for Neuroscience and Human Behavior, University of California , Los Angeles, CA 90095 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4137-1655","authenticated-orcid":false,"given":"Sulayman","family":"Dib-Hajj","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale University School of Medicine , New Haven, CT 06510 ,","place":["USA"]},{"name":"Center for Neuroscience and Regeneration Research, Yale University School of Medicine , New Haven, CT 06510 ,","place":["USA"]},{"name":"Center for Restoration of Function after Nervous System Injury, Veterans Affairs Medical Center , West Haven, CT 06516 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen G","family":"Waxman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale University School of Medicine , New Haven, CT 06510 ,","place":["USA"]},{"name":"Center for Neuroscience and Regeneration Research, Yale University School of Medicine , New Haven, CT 06510 ,","place":["USA"]},{"name":"Center for Restoration of Function after Nervous System Injury, Veterans Affairs Medical Center , West Haven, CT 06516 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6636-3897","authenticated-orcid":false,"given":"Clifford J","family":"Woolf","sequence":"additional","affiliation":[{"name":"F.M. 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