How to cite this article: Butler MG, Dagenais SL, Rockson SG, Glover TW. 2007. A novel VEGFR3 mutation causes Milroy disease. Am J Med Genet Part A 143A:1212–1217.
A novel VEGFR3 mutation causes Milroy disease†
Article first published online: 25 APR 2007
Copyright © 2007 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 143A, Issue 11, pages 1212–1217, 1 June 2007
How to Cite
Butler, M. G., Dagenais, S. L., Rockson, S. G. and Glover, T. W. (2007), A novel VEGFR3 mutation causes Milroy disease. Am. J. Med. Genet., 143A: 1212–1217. doi: 10.1002/ajmg.a.31703
- Issue published online: 21 MAY 2007
- Article first published online: 25 APR 2007
- Manuscript Accepted: 1 JAN 2007
- Manuscript Received: 31 JUL 2006
- National Institutes of Health. Grant Number: HL71206
- Glover from the National Heart, Lung, and Blood Institute
- Michigan Predoctoral Training Program in Genetics. Grant Number: 5T32GM007544-29
- Milroy disease;
Milroy disease, also known as primary congenital lymphedema, is a hereditary form of lymphedema with autosomal dominant inheritance. Individuals with Milroy disease are typically characterized by congenital onset of lymphedema of the lower limbs due to hypoplasia of the lymphatic vessels. The genetic basis of most cases of Milroy disease has not been established, although mutations in the vascular endothelial growth factor receptor VEGFR3 (FLT-4) are responsible for some cases with 17 mutations described to date. In this report, we describe a novel VEGFR3 mutation in exon 22 in a four-generation family in which congenital lymphedema segregates in an autosomal dominant manner. In addition to lymphedema, affected family members had other clinical manifestations associated with Milroy disease including hydrocele, ski jump toenails, large caliber veins, and subcutaneous thickening. We screened VEGFR3 for mutations which revealed a novel 3059A > T transversion in exon 22 resulting in Q1020L missense mutation in the second tyrosine kinase domain of VEGFR3. This mutant allele segregated with lymphedema among affected individuals with incomplete penetrance. This is the first report of an exon 22 mutation in Milroy disease. © 2007 Wiley-Liss, Inc.