{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T15:46:11Z","timestamp":1776872771551,"version":"3.51.2"},"reference-count":20,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,6,26]],"date-time":"2020-06-26T00:00:00Z","timestamp":1593129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["303778303778"],"award-info":[{"award-number":["303778303778"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["273612"],"award-info":[{"award-number":["273612"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["265982"],"award-info":[{"award-number":["265982"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Milroy\u2010like disease is the diagnostic definition used for patients with phenotypes that resemble classic Milroy disease (MD) but are negative to genetic testing for <jats:italic>FLT4<\/jats:italic>. In this study, we aimed at performing a genetic characterization and biochemical analysis of VEGF\u2010C variations found in a female proband born with congenital edema consistent with Milroy\u2010like disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The proband underwent next\u2010generation sequencing\u2010based genetic testing for a panel of genes associated with known forms of hereditary lymphedema. Segregation analysis was performed on family members by direct sequencing. In vitro studies were performed to evaluate the role of a novel identified variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two <jats:italic>VEGF\u2010C<\/jats:italic> variations were found in the proband, a novel p.(Ser65Arg) and a pathogenic c.148\u20103_148\u20102delCA, of paternal and maternal origin, respectively. Functional characterization of the p.(Ser65Arg) variation in vitro showed alterations in VEGF\u2010C processing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings reveal an interesting case in which biallelic variants in <jats:italic>VEGF\u2010C<\/jats:italic> are found in a patient with Milroy\u2010like lymphedema. These data expand our understanding of the etiology of congenital Milroy\u2010like lymphedema.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1389","type":"journal-article","created":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T10:36:05Z","timestamp":1593254165000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Investigation on the role of biallelic variants in <i>VEGF\u2010C<\/i> found in a patient affected by Milroy\u2010like lymphedema"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1500-1914","authenticated-orcid":false,"given":"Sylvain","family":"Mukenge","sequence":"first","affiliation":[{"name":"Department of Surgery Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sawan 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