{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T03:11:55Z","timestamp":1772766715626,"version":"3.50.1"},"reference-count":118,"publisher":"Portland Press Ltd.","issue":"22","license":[{"start":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T00:00:00Z","timestamp":1731024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,11,20]]},"abstract":"<jats:p>Erythrokeratodermia variabilis et progressiva (EKVP) is a rare hereditary skin disorder characterized by hyperkeratotic plaques and erythematous patches that progressively worsen with age. This disorder has been associated with variants in three connexin encoding genes (GJA1, GJB3, GJB4) and four unrelated genes (KRT83, KDSR, TRPM4, PERP). Most cases of connexin-linked EKVP exhibit an autosomal dominant mode of inheritance, with rare autosomal recessive cases. Collectively, evidence suggests that connexin variants associated with EKVP elicit a plethora of molecular defects including impaired gap junction (GJ) formation, dysregulated hemichannel and\/or GJ channel function, cytotoxicity, dominant disruption of co-expressed connexins, and\/or altered turnover kinetics. Here, we review the progress made in understanding the genetic and molecular basis of EKVP associated with connexin gene variants. We also discuss the landscape of treatment options used for this disorder and the future directions for research into this rare condition.<\/jats:p>","DOI":"10.1042\/bcj20240374","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T12:36:04Z","timestamp":1731069364000},"page":"1639-1655","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The genetic and molecular basis of a connexin-linked skin disease"],"prefix":"10.1042","volume":"481","author":[{"given":"Sergiu A.","family":"Lucaciu","sequence":"first","affiliation":[{"name":"1Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada"},{"name":"2Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4568-3285","authenticated-orcid":false,"given":"Dale W.","family":"Laird","sequence":"additional","affiliation":[{"name":"1Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada"},{"name":"2Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2024,11,8]]},"reference":[{"key":"2024110812354237600_BCJ-2024-0374CC1","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","year":"2021","journal-title":"Nature"},{"key":"2024110812354237600_BCJ-2024-0374CC2","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/nature07869","article-title":"Structure of the connexin 26 gap junction channel at 3.5 A resolution","volume":"458","year":"2009","journal-title":"Nature"},{"key":"2024110812354237600_BCJ-2024-0374CC3","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.str.2022.02.010","article-title":"Conformational changes and CO2-induced channel gating in connexin26","volume":"30","year":"2022","journal-title":"Structure"},{"key":"2024110812354237600_BCJ-2024-0374CC4","doi-asserted-by":"publisher","first-page":"eadh4890","DOI":"10.1126\/sciadv.adh4890","article-title":"Structures of wild-type and selected CMT1X mutant connexin 32 gap junction channels and hemichannels","volume":"9","year":"2023","journal-title":"Sci. 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