Investigation on the role of biallelic variants in VEGF-C found in a patient affected by Milroy-like lymphedema

Sylvain Mukenge, Sawan K. Jha, Marco Catena, Elena Manara, Veli Matti Leppänen, Elisa Lenti, Daniela Negrini, Matteo Bertelli, Andrea Brendolan, Michael Jeltsch, Luca Aldrighetti

Research output: Contribution to journalArticlepeer-review


Background: Milroy-like disease is the diagnostic definition used for patients with phenotypes that resemble classic Milroy disease (MD) but are negative to genetic testing for FLT4. In this study, we aimed at performing a genetic characterization and biochemical analysis of VEGF-C variations found in a female proband born with congenital edema consistent with Milroy-like disease. Methods: The proband underwent next-generation sequencing-based genetic testing for a panel of genes associated with known forms of hereditary lymphedema. Segregation analysis was performed on family members by direct sequencing. In vitro studies were performed to evaluate the role of a novel identified variant. Results: Two VEGF-C variations were found in the proband, a novel p.(Ser65Arg) and a pathogenic c.148-3_148-2delCA, of paternal and maternal origin, respectively. Functional characterization of the p.(Ser65Arg) variation in vitro showed alterations in VEGF-C processing. Conclusions: Our findings reveal an interesting case in which biallelic variants in VEGF-C are found in a patient with Milroy-like lymphedema. These data expand our understanding of the etiology of congenital Milroy-like lymphedema.

Original languageEnglish
Article numbere1389
JournalMolecular Genetics and Genomic Medicine
Issue number9
Publication statusPublished - Sep 1 2020


  • lymphatic system
  • Milroy disease
  • mutation
  • primary lymphedema
  • VEGF-C

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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