{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:15:52Z","timestamp":1790414152006,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,9,4]],"date-time":"2006-09-04T00:00:00Z","timestamp":1157328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:p>Mutations in the vascular endothelial growth factor receptor 3 gene, <jats:italic>VEGFR3\/FLT4<\/jats:italic>, have been identified in a subset of families with hereditary lymphedema type I or Milroy disease (MIM 153100). Individuals carrying a <jats:italic>VEGFR3<\/jats:italic> mutation exhibit congenital edema of the lower limbs, usually bilaterally and below the knees, sometimes associated with cellulitis, prominent veins, papillomatosis, upturned toenails, and hydrocele. In this study, we report the first <jats:italic>de novo VEGFR3<\/jats:italic> mutation in a patient with sporadic congenital lymphedema. We also describe three other families with a <jats:italic>VEGFR3<\/jats:italic> mutation. In each family, one individual had an atypical clinical presentation of hereditary lymphedema type I, whereas the others had the classical <jats:italic>VEGFR3<\/jats:italic> mutation\u2010caused phenotype. The atypical presentations included pre\u2010natal pleural effusion, spontaneous resorption of lymphedema and elephantiasis. Three of the four identified mutations were novel. These data show that <jats:italic>de novo VEGFR3<\/jats:italic> mutations may be present in patients without family history of congenital lymphedema. This has implications for follow\u2010up care, as such individuals have nearly a 50% risk for occurrence of lymphedema in their children. Our findings also indicate that although most patients with a <jats:italic>VEGFR3<\/jats:italic> mutation have the well\u2010defined phenotype for hereditary lymphedema type I, there are exceptions that should be considered in genetic counseling. Because <jats:italic>VEGFR3<\/jats:italic> mutation can cause generalized lymphatic dysfunction and can thus result in hydrops fetalis, <jats:italic>VEGFR3<\/jats:italic> screening should be added to the investigation of cases of hydrops fetalis of an unknown etiology.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2006.00687.x","type":"journal-article","created":{"date-parts":[[2006,9,4]],"date-time":"2006-09-04T15:00:34Z","timestamp":1157382034000},"page":"330-335","source":"Crossref","is-referenced-by-count":74,"title":["Hereditary lymphedema type I associated with <i>VEGFR3<\/i> mutation: the first <i>de novo<\/i> case and atypical 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