Segregation Analysis of Rare <i>NRP1</i> and <i>NRP2</i> Variants in Families with Lymphedema

• Main Authors: Sandro Michelini, Bruno Amato, Maurizio Ricci, Sercan Kenanoglu, Dominika Veselenyiova, Danjela Kurti, Mirko Baglivo, Elena Manara, Munis Dundar, Juraj Krajcovic, Syed Hussain Basha, Sasi Priya, Roberta Serrani, Giacinto A. D. Miggiano, Barbara Aquilanti, Giuseppina Matera, Valeria Velluti, Lucilla Gagliardi, Astrit Dautaj, Matteo Bertelli
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: Genes
• Subjects: NRP1; NRP2; NGS; lymphedema; genetic diagnostics
• Online Access: https://www.mdpi.com/2073-4425/11/11/1361

Neuropilins are transmembrane coreceptors expressed by endothelial cells and neurons. NRP1 and NRP2 bind a variety of ligands, by which they trigger cell signaling, and are important in the development of lymphatic valves and lymphatic capillaries, respectively. This study focuses on identifying rare variants in the <i>NRP1</i> and <i>NRP2</i> genes that could be linked to the development of lymphatic malformations in patients diagnosed with lymphedema. Two hundred and thirty-five Italian lymphedema patients, who tested negative for variants in known lymphedema genes, were screened for variants in <i>NRP1</i> and <i>NRP2</i>. Two probands carried variants in <i>NRP1</i> and four in <i>NRP2</i>. The variants of both genes segregated with lymphedema in familial cases. Although further functional and biochemical studies are needed to clarify their involvement with lymphedema and to associate <i>NRP1</i> and <i>NRP2</i> with lymphedema, we suggest that it is worthwhile also screening lymphedema patients for these two new candidate genes.