{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:29:17Z","timestamp":1790994557954,"version":"4.1.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260391 82372541 82360448"],"award-info":[{"award-number":["82260391 82372541 82360448"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Primary lymphedema (PL) is a chronic condition characterized by abnormal swelling of tissues due to impaired lymphatic drainage, leading to increased deposition of adipose tissue and fibrosis. Although several pathogenic variants in genes associated with PL have been identified, a significant number of cases remain unexplained, suggesting the possibility of undiscovered genetic links.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>This report describes a novel heterozygous mutation in the PROX1 gene (c.1019C&amp;gt;G, p.S340C) identified in a 59-year-old male patient with PL affecting both upper and lower extremities, indicating its potential role in lymphatic dysfunction. A comprehensive treatment strategy\u2014combining conservative decongestive therapy for the less severely affected upper limb with radical reduction while preserving perforators (RRPP) and vascularized lymph node transfer (VLNT) for the severely affected lower limb\u2014resulted in significant improvements in limb circumference, lymphatic transport, and overall quality of life.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This report highlights the efficacy of combining RRPP and SC-VLNT in treating advanced-stage PL and emphasizes the importance of considering genetic factors in the management of this complex disease.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fgene.2025.1560471","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T04:10:24Z","timestamp":1751515824000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Case Report: Surgical management of primary lymphedema with a novel PROX1 mutation involving upper and lower limbs"],"prefix":"10.3389","volume":"16","author":[{"given":"Junzhe","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangliang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangkui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bihua","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shune","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengliang","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1038\/nature04480","article-title":"Lymphangiogenesis in development and human disease","volume":"438","author":"Alitalo","year":"2005","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"7414","DOI":"10.3390\/ijms23137414","article-title":"Low efficacy of genetic tests for the diagnosis of primary lymphedema prompts novel insights into the underlying molecular pathways","volume":"23","author":"Bonetti","year":"2022","journal-title":"Int. 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