{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T09:48:54Z","timestamp":1770457734696,"version":"3.49.0"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,11,28]],"date-time":"2020-11-28T00:00:00Z","timestamp":1606521600000},"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":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>We developed a Next\u2010Generation\u2010Sequencing (NGS) protocol to screen the most frequent genetic variants related to lymphedema and a group of candidate genes. The aim of the study was to find the genetic cause of lymphedema in the analyzed patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We sequenced a cohort of 246 Italian patients with lymphatic malformations. In the first step, we analyzed genes known to be linked to lymphedema: 235 out of 246 patients tested negative for the most frequent variants and underwent testing for variants in a group of candidate genes, including the <jats:italic>NOTCH1<\/jats:italic> gene, selected from the database of mouse models. We also performed in silico analysis to observe molecular interactions between the wild\u2010type and the variant amino acids and other protein residues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seven out of 235 probands, five with sporadic and two with familial lymphedema, were found to carry rare missense variants in the <jats:italic>NOTCH1<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results propose that <jats:italic>NOTCH1<\/jats:italic> could be a novel candidate for genetic predisposition to lymphedema.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1529","type":"journal-article","created":{"date-parts":[[2020,11,28]],"date-time":"2020-11-28T12:50:39Z","timestamp":1606567839000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["<i>NOTCH1<\/i>: Review of its role in lymphatic development and study of seven families with rare pathogenic variants"],"prefix":"10.1002","volume":"9","author":[{"given":"Sandro","family":"Michelini","sequence":"first","affiliation":[{"name":"Department of Vascular Rehabilitation San Giovanni Battista Hospital Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Ricci","sequence":"additional","affiliation":[{"name":"Division of Rehabilitation Medicine Azienda Ospedaliero\u2010Universitaria Ospedali Riuniti di Ancona Ancona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Serrani","sequence":"additional","affiliation":[{"name":"Division of Rehabilitation Medicine Azienda Ospedaliero\u2010Universitaria Ospedali Riuniti di Ancona Ancona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shila","family":"Barati","sequence":"additional","affiliation":[{"name":"MAGI EUREGIO Bolzano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sercan","family":"Kenanoglu","sequence":"additional","affiliation":[{"name":"MAGI EUREGIO Bolzano Italy"},{"name":"Department of Medical Genetics Faculty of Medicine Erciyes University Kayseri Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominika","family":"Veselenyiova","sequence":"additional","affiliation":[{"name":"MAGI EUREGIO Bolzano Italy"},{"name":"Department of Biology Faculty of Natural Sciences University of Ss. Cyril and Methodius in Trnava Trnava Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danjela","family":"Kurti","sequence":"additional","affiliation":[{"name":"MAGI EUREGIO Bolzano Italy"},{"name":"MAGI\u2010Balkans Tirana Albania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3924-3195","authenticated-orcid":false,"given":"Mirko","family":"Baglivo","sequence":"additional","affiliation":[{"name":"MAGI EUREGIO Bolzano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed Hussain","family":"Basha","sequence":"additional","affiliation":[{"name":"Innovative Informatica Technologies Hyderabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sasi","family":"Priya","sequence":"additional","affiliation":[{"name":"Innovative Informatica Technologies Hyderabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Astrit","family":"Dautaj","sequence":"additional","affiliation":[{"name":"MAGI\u2010Balkans Tirana Albania"},{"name":"EBTNA\u2010LAB Rovereto Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Munis","family":"Dundar","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Faculty of Medicine Erciyes University Kayseri Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juraj","family":"Krajcovic","sequence":"additional","affiliation":[{"name":"Department of Biology Faculty of Natural Sciences University of Ss. Cyril and Methodius in Trnava Trnava Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Bertelli","sequence":"additional","affiliation":[{"name":"MAGI EUREGIO Bolzano Italy"},{"name":"EBTNA\u2010LAB Rovereto Italy"},{"name":"MAGI'S LAB Rovereto Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,11,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20000814)93:4<328::AID-AJMG13>3.0.CO;2-0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq662"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-421"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.24129"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03940"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.200900140"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20065"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102017\u2010105064"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.101188"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-11-319129"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.313250"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1818"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_16_1","volume-title":"Dassault Syst\u00e8mes BIOVIA. 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