{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:09:46Z","timestamp":1783573786468,"version":"3.55.0"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,3,10]],"date-time":"2020-03-10T00:00:00Z","timestamp":1583798400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,3,10]],"date-time":"2020-03-10T00:00:00Z","timestamp":1583798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD093735"],"award-info":[{"award-number":["R01HD093735"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Extracranial arteriovenous malformation (AVM) is most commonly caused by <jats:italic>MAP2K1<\/jats:italic> mutations in the endothelial cell. The purpose of this study was to determine if local tissue overgrowth associated with AVM is caused by direct or indirect effects of the <jats:italic>MAP2K1<\/jats:italic> mutation (i.e., cell-autonomous or cell-non autonomous). Because cartilage does not have blood vessels, we studied ear AVMs to determine if overgrown cartilage contained AVM-causing mutations. Cartilage was separated from its surrounding tissue and isolated by laser capture microdissection. Droplet digital PCR (ddPCR) was used to identify <jats:italic>MAP2K1<\/jats:italic> mutations. <jats:italic>MAP2K1<\/jats:italic> (p.K57N) variants were present in the tissue adjacent to the cartilage [mutant allele frequency (MAF) 6\u20138%], and were enriched in endothelial cells (MAF 51%) compared to non-endothelial cells (MAF 0%). <jats:italic>MAP2K1<\/jats:italic> mutations were not identified in the overgrown cartilage, and thus local cartilage overgrowth likely results from the effects of adjacent mutant blood vessels (i.e., cell-non autonomous).<\/jats:p>","DOI":"10.1038\/s41598-020-61444-x","type":"journal-article","created":{"date-parts":[[2020,3,10]],"date-time":"2020-03-10T11:03:11Z","timestamp":1583838191000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Arteriovenous Malformation MAP2K1 Mutation Causes Local Cartilage Overgrowth by a Cell-Non Autonomous Mechanism"],"prefix":"10.1038","volume":"10","author":[{"given":"Dennis J.","family":"Konczyk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy A.","family":"Goss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J.","family":"Smits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.","family":"Sudduth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyaa","family":"Al-Ibraheemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arin K.","family":"Greene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,10]]},"reference":[{"key":"61444_CR1","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1097\/01.PRS.0000154207.87313.DE","volume":"115","author":"JK Wu","year":"2005","unstructured":"Wu, J. K. et al. Auricular arteriovenous malformation: Evaluation, management, and outcome. Plast. Reconstr. Surg. 115, 985\u2013995 (2005).","journal-title":"Plast. Reconstr. Surg."},{"key":"61444_CR2","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1097\/PRS.0b013e3181d18070","volume":"125","author":"AS Liu","year":"2010","unstructured":"Liu, A. S., Mulliken, J. B., Zurakowski, D., Fishman, S. J. & Greene, A. K. Extracranial Arteriovenous Malformations: Natural Progression and Recurrence after Treatment. Plast. Reconstr. Surg. 125, 1185\u20131194 (2010).","journal-title":"Plast. Reconstr. Surg."},{"key":"61444_CR3","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1016\/j.ajhg.2017.01.018","volume":"100","author":"JA Couto","year":"2017","unstructured":"Couto, J. A. et al. Somatic MAP2K1 Mutations Are Associated with Extracranial Arteriovenous Malformation. Am. J. Hum. Genet. 100, 546\u2013554 (2017).","journal-title":"Am. J. Hum. 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