We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
A Novel Splice-Site Mutation in VEGFC Is Associated with Congenital Primary Lymphoedema of Gordon.
- Authors
Nadarajah, Noeline; Schulte, Dörte; McConnell, Vivienne; Martin-Almedina, Silvia; Karapouliou, Christina; Mortimer, Peter S.; Jeffery, Steve; Schulte-Merker, Stefan; Gordon, Kristiana; Mansour, Sahar; Ostergaard, Pia
- 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. <italic>VEGFC</italic>, 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 <italic>VEGFC</italic>. The mutation induced skipping of exon 2 of <italic>VEGFC</italic> 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.
- Subjects
LYMPHEDEMA; ENDOTHELIAL growth factors; ZEBRA danio; LYMPHANGIOSARCOMA; ELEPHANTIASIS
- Publication
International Journal of Molecular Sciences, 2018, Vol 19, Issue 8, p2259
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms19082259