{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:47:07Z","timestamp":1791895627588,"version":"4.3.4"},"reference-count":24,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Voltage\u2010gated sodium channels are essential for the generation and conduction of electrical impulses in excitable cells. Sodium channel Na<jats:sub>v<\/jats:sub>1.7, encoded by the SCN9A\u2010gene, has been of special interest in the last decades because missense gain\u2010of\u2010function mutations have been linked to a spectrum of neuropathic pain conditions, including inherited erythermalgia (IEM), paroxysmal extreme pain disorder (PEPD), and small fiber neuropathy (SFN).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this case report, we present a 61\u2010year\u2010old woman who was referred to our tertiary referral center in a standard day care setting with suspicion of SFN. We performed additional investigations: skin biopsy to determine the intra\u2010epidermal nerve fiber density (IENFD), quantitative sensory testing (QST), and blood examination (including DNA analysis) for possible underlying conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The patient showed a clinical picture that fulfilled the criteria of IEM, PEPD, and SFN. DNA analysis revealed the heterozygous variant c.554G\u2009&gt;\u2009A in the SCN9A\u2010gene (OMIM 603415). This variant has already been described in all three human pain conditions separately, but never in one patient having symptoms of all three conditions. Because its pathogenicity has never been functionally confirmed, the variant is classified as a variance of unknown significance (VUS)\/risk factor. This suggests that another genetic and\/or environmental substrate plays a role in the development of neuropathic conditions like described.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We have described this as the <jats:italic>SCN9A<\/jats:italic>\u2010pain triangle phenomenon. Treatment should focus on pain management, genetic counseling, and improving\/maintaining quality of life by treating symptoms and, if indicated, starting a rehabilitation program.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2026","type":"journal-article","created":{"date-parts":[[2022,9,17]],"date-time":"2022-09-17T06:40:42Z","timestamp":1663396842000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pain triangle phenomenon in possible association with <scp>SCN9A<\/scp>: A case report"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8132-1532","authenticated-orcid":false,"given":"Maurice","family":"Sopacua","sequence":"first","affiliation":[{"name":"Department of Neurology, School of Mental Health and Neuroscience Maastricht University Medical Center+  Maastricht The Netherlands"},{"name":"Department of Rehabilitation Medicine Libra Revalidatie &amp; Audiologie  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janneke G. J.","family":"Hoeijmakers","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Mental Health and Neuroscience Maastricht University Medical Center+  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneke J.","family":"van der Kooi","sequence":"additional","affiliation":[{"name":"Department of Neurology Amsterdam University Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingemar S. J.","family":"Merkies","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Mental Health and Neuroscience Maastricht University Medical Center+  Maastricht The Netherlands"},{"name":"Department of Neurology Cura\u00e7ao Medical Center  Willemstad Cura\u00e7ao"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina G.","family":"Faber","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Mental Health and Neuroscience Maastricht University Medical Center+  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0238467"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2018.10.024"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40266-015-0283-8"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-4-1"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-016-1430-1"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13508"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-4-37"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh514"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2005.23737.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2018-319042"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.01.079"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22485"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000268065.16865.5f"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2011.09.008"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182574f12"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws187"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3424-06.2006"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.4161\/chan.3.4.9341"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2010.00271.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-014-2819-2"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/jns.12298"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000000476"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70150-4"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2007.09.027"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2026","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.2026","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T09:57:24Z","timestamp":1692698244000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,16]]},"references-count":24,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1002\/mgg3.2026"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2026","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,16]]},"assertion":[{"value":"2021-12-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2026"}}