Nadarajah, N;
Schulte, D;
McConnell, V;
Martin-Almedina, S;
Karapouliou, C;
Mortimer, PS;
Jeffery, S;
Schulte-Merker, S;
Gordon, K;
Mansour, S;
et al.
Nadarajah, N; Schulte, D; McConnell, V; Martin-Almedina, S; Karapouliou, C; Mortimer, PS; Jeffery, S; Schulte-Merker, S; Gordon, K; Mansour, S; Ostergaard, P
(2018)
A Novel Splice-Site Mutation in VEGFC Is Associated with Congenital Primary Lymphoedema of Gordon.
Int J Mol Sci, 19 (8).
p. 2259.
ISSN 1422-0067
https://doi.org/10.3390/ijms19082259
SGUL Authors: Jeffery, Stephen Mortimer, Peter Sydney Ostergaard, Pia Mansour, Sahar Martin Almedina, Silvia Mansour, Sahar
Abstract
Lymphedema is characterized by chronic swelling of any body part caused by malfunctioning or obstruction in the lymphatic system. Primary lymphedema is often considered genetic in origin. VEGFC, which is a gene encoding the ligand for the vascular endothelial growth factor receptor 3 (VEGFR3/FLT4) and important for lymph vessel development during lymphangiogenesis, has been associated with a specific subtype of primary lymphedema. Through Sanger sequencing of a proband with bilateral congenital pedal edema resembling Milroy disease, we identified a novel mutation (NM_005429.2; c.361+5G>A) in VEGFC. The mutation induced skipping of exon 2 of VEGFC resulting in a frameshift and the introduction of a premature stop codon (p.Ala50ValfsTer18). The mutation leads to a loss of the entire VEGF-homology domain and the C-terminus. Expression of this Vegfc variant in the zebrafish floorplate showed that the splice-site variant significantly reduces the biological activity of the protein. Our findings confirm that the splice-site variant, c.361+5G>A, causes the primary lymphedema phenotype in the proband. We examine the mutations and clinical phenotypes of the previously reported cases to review the current knowledge in this area.
Item Type: |
Article
|
Additional Information: |
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: |
FLT4, Milroy, VEGFC, VEGFR3, primary lymphedema, Chemical Physics, 0399 Other Chemical Sciences, 0604 Genetics, 0699 Other Biological Sciences |
SGUL Research Institute / Research Centre: |
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS) |
Journal or Publication Title: |
Int J Mol Sci |
ISSN: |
1422-0067 |
Language: |
eng |
Dates: |
Date | Event |
---|
1 August 2018 | Published | 27 July 2018 | Accepted |
|
Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
|
PubMed ID: |
30071673 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/110040 |
Publisher's version: |
https://doi.org/10.3390/ijms19082259 |
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