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Updated: Dec 12, 2025

Isolation of Human Lymphatic Endothelial Cells by Multi-parameter Fluorescence-activated Cell Sorting
Published on: May 1, 2015
Two rare PROX1 variants in patients with lymphedema
Maurizio Ricci1, Bruno Amato2, Shila Barati3
1Division of Rehabilitation Medicine, Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Ancona, Italy.
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.
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