{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:49:11Z","timestamp":1785332951458,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,5]],"date-time":"2020-08-05T00:00:00Z","timestamp":1596585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009890","name":"Provincia Autonoma di Trento","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009890","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":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The <jats:italic>PROX1<\/jats:italic> gene is specifically expressed in a subpopulation of endothelial cells that, by budding and sprouting, give rise to the lymphatic system. It also plays a critical role in neurogenesis and during development of many organs, such as the eye lens, liver, and pancreas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used next\u2010generation sequencing (NGS) to sequence the DNA of a cohort of 246 Italian patients with lymphatic malformations. We first investigated 29 known disease\u2010causing genes: 235 of 246 patients tested negative and were then retested for a group of candidate genes, including <jats:italic>PROX1<\/jats:italic>, selected from a database of mouse models. The aim of the study was to define these patients\u2019 genotypes and explore the role of the candidate gene <jats:italic>PROX1<\/jats:italic> in lymphedema.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two of 235 probands were found to carry rare heterozygous missense variants in <jats:italic>PROX1<\/jats:italic>. In silico analysis of these variants\u2014p.(Leu590His) and p.(Gly106Asp)\u2014indicates that the overall protein structure was altered by changes in interactions between nearby residues, leading to functional protein defects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results suggest that <jats:italic>PROX1<\/jats:italic> is a new candidate gene for predisposition to lymphedema.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1424","type":"journal-article","created":{"date-parts":[[2020,8,5]],"date-time":"2020-08-05T13:27:38Z","timestamp":1596634058000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Two rare <i>PROX1<\/i> variants in patients with lymphedema"],"prefix":"10.1002","volume":"8","author":[{"given":"Maurizio","family":"Ricci","sequence":"first","affiliation":[{"name":"Division of Rehabilitation Medicine Azienda Ospedaliero\u2010Universitaria Ospedali Riuniti di Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Amato","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery University Federico II of Naples Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shila","family":"Barati","sequence":"additional","affiliation":[{"name":"MAGI Euregio Bolzano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Compagna","sequence":"additional","affiliation":[{"name":"Department of Public Health University of Naples Federico II Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominika","family":"Veselenyiova","sequence":"additional","affiliation":[{"name":"MAGI Euregio Bolzano Italy"},{"name":"Department of Biology Faculty of Natural Sciences University of Ss. 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