{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:08:40Z","timestamp":1791353320846,"version":"4.3.1"},"reference-count":56,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009890","name":"Provincia Autonoma di Trento","doi-asserted-by":"publisher","award":["dpg 1045\/2017"],"award-info":[{"award-number":["dpg 1045\/2017"]}],"id":[{"id":"10.13039\/501100009890","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Lipedema is a disabling disease characterized by symmetric enlargement of the lower and\/or upper limbs due to deposits of subcutaneous fat, that is easily misdiagnosed. Lipedema can be primary or syndromic, and can be the main feature of phenotypically overlapping disorders. The aim of this study was to design a next-generation sequencing (NGS) panel to help in the diagnosis of lipedema by identifying genes specific for lipedema but also genes for overlapping diseases, and targets for tailored treatments. We developed an NGS gene panel consisting of 305 genes potentially associated with lipedema and putative overlapping diseases relevant to lipedema. The genomes of 162 Italian and American patients with lipedema were sequenced. Twenty-one deleterious variants, according to 3 out of 5 predictors, were detected in PLIN1, LIPE, ALDH18A1, PPARG, GHR, INSR, RYR1, NPC1, POMC, NR0B2, GCKR, PPARA in 17 patients. This extended NGS-based approach has identified a number of gene variants that may be important in the diagnosis of lipedema, that may affect the phenotypic presentation of lipedema or that may cause disorders that could be confused with lipedema. This tool may be important for the diagnosis and treatment of people with pathologic subcutaneous fat tissue accumulation.<\/jats:p>","DOI":"10.3390\/jpm12020268","type":"journal-article","created":{"date-parts":[[2022,2,13]],"date-time":"2022-02-13T21:08:43Z","timestamp":1644786523000},"page":"268","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["A Multi-Gene Panel to Identify Lipedema-Predisposing Genetic Variants by a Next-Generation Sequencing Strategy"],"prefix":"10.3390","volume":"12","author":[{"given":"Sandro","family":"Michelini","sequence":"first","affiliation":[{"name":"Vascular Diagnostics and Rehabilitation Service, Marino Hospital, ASL Roma 6, 00047 Marino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Herbst","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Research, Total Lipedema Care, Los Angeles, CA 90211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenza","family":"Precone","sequence":"additional","affiliation":[{"name":"MAGI EUREGIO, 39100 Bolzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1176-3359","authenticated-orcid":false,"given":"Elena","family":"Manara","sequence":"additional","affiliation":[{"name":"MAGI\u2019S LAB, 38068 Rovereto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Marceddu","sequence":"additional","affiliation":[{"name":"MAGI EUREGIO, 39100 Bolzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6385-3444","authenticated-orcid":false,"given":"Astrit","family":"Dautaj","sequence":"additional","affiliation":[{"name":"MAGI\u2019S LAB, 38068 Rovereto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1974-4937","authenticated-orcid":false,"given":"Paolo Enrico","family":"Maltese","sequence":"additional","affiliation":[{"name":"MAGI\u2019S LAB, 38068 Rovereto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5551-7520","authenticated-orcid":false,"given":"Stefano","family":"Paolacci","sequence":"additional","affiliation":[{"name":"MAGI\u2019S LAB, 38068 Rovereto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5344-4890","authenticated-orcid":false,"given":"Maria Rachele","family":"Ceccarini","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, Italy"},{"name":"C.I.B., Consorzio Interuniversitario per le Biotecnologie, 34148 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9637-6579","authenticated-orcid":false,"given":"Tommaso","family":"Beccari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, Italy"},{"name":"C.I.B., Consorzio Interuniversitario per le Biotecnologie, 34148 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Sorrentino","sequence":"additional","affiliation":[{"name":"MAGI EUREGIO, 39100 Bolzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Aquilanti","sequence":"additional","affiliation":[{"name":"UOC Nutrizione Clinica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7684-5785","authenticated-orcid":false,"given":"Valeria","family":"Velluti","sequence":"additional","affiliation":[{"name":"UOC Nutrizione Clinica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Matera","sequence":"additional","affiliation":[{"name":"UOC Nutrizione Clinica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucilla","family":"Gagliardi","sequence":"additional","affiliation":[{"name":"UOC Nutrizione Clinica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacinto Abele Donato","family":"Miggiano","sequence":"additional","affiliation":[{"name":"UOC Nutrizione Clinica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9552-221X","authenticated-orcid":false,"given":"Matteo","family":"Bertelli","sequence":"additional","affiliation":[{"name":"MAGI EUREGIO, 39100 Bolzano, Italy"},{"name":"MAGI\u2019S LAB, 38068 Rovereto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1097\/PRS.0000000000006280","article-title":"New Insights on Lipedema: The Enigmatic Disease of the Peripheral Fat","volume":"144","author":"Bauer","year":"2019","journal-title":"Plast. Reconstr. 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