Abstract
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 NRP1 and NRP2 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 NRP1 and NRP2. Two probands carried variants in NRP1 and four in NRP2. 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 NRP1 and NRP2 with lymphedema, we suggest that it is worthwhile also screening lymphedema patients for these two new candidate genes.
Highlights
Neuropilins 1 and 2 are transmembrane coreceptor proteins encoded by the NRP1 and NRP2 genes
We report our findings from screening a cohort of 235 patients, negative for variants in the said 29 genes, for variants in the neuropilin-coding genes NRP1 and NRP2
Our results showed rare variants in NRP1 and NRP2 in patients who tested negative for variants in the 29 genes already associated with lymphedema
Summary
Neuropilins 1 and 2 are transmembrane coreceptor proteins encoded by the NRP1 and NRP2 genes They were first identified in the nervous system of Xenopus laevis embryos [1,2]. The two neuropilins have a very short intracellular domain (only about 40 amino acids long) and a longer extracellular region. Both neuropilins complex a large variety of ligands, by which they take part in cell signaling. These transmembrane proteins have a critical role in the regulation of vascular and neural development through binding vascular endothelial growth factors (VEGFs) and semaphorins [5]. NRP1 and NRP2 bind other ligands—for instance, hepatocyte growth factor (HGF) [7], EGF receptor [8] and an adhesion receptor
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