Two rare PROX1 variants in patients with lymphedema

Maurizio Ricci, Bruno Amato, Shila Barati, Rita Compagna, Dominika Veselenyiova, Sercan Kenanoglu, Liborio Stuppia, Tommaso Beccari, Mirko Baglivo, Danjela Kurti, Juraj Krajcovic, Roberta Serrani, Munis Dundar, Syed H. Basha, Pietro Chiurazzi, Matteo Bertelli

Research output: Contribution to journalArticlepeer-review


Background: The PROX1 gene is specifically expressed in a subpopulation of endothelial cells that, by budding and sprouting, give rise to the lymphatic system. It also plays a critical role in neurogenesis and during development of many organs, such as the eye lens, liver, and pancreas. Methods: We used next-generation sequencing (NGS) to sequence the DNA of a cohort of 246 Italian patients with lymphatic malformations. We first investigated 29 known disease-causing genes: 235 of 246 patients tested negative and were then retested for a group of candidate genes, including PROX1, selected from a database of mouse models. The aim of the study was to define these patients’ genotypes and explore the role of the candidate gene PROX1 in lymphedema. Results: Two of 235 probands were found to carry rare heterozygous missense variants in PROX1. In silico analysis of these variants—p.(Leu590His) and p.(Gly106Asp)—indicates that the overall protein structure was altered by changes in interactions between nearby residues, leading to functional protein defects. Conclusions: Our results suggest that PROX1 is a new candidate gene for predisposition to lymphedema.

Original languageEnglish
Article numbere1424
JournalMolecular Genetics and Genomic Medicine
Issue number10
Publication statusPublished - Oct 1 2020
Externally publishedYes


  • genetic diagnosis
  • lymphedema
  • next-generation sequencing (NGS)
  • PROX1

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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