Primary lymphedema is a condition in which there is a deficiency of lymphatic drainage, leading to swelling, frequent recurrent cellulites, and disfigurement of the affected limb or lower torso, in the absence of vascular, cardiac, surgical, renal or hepatic causes for the edema. The PI has mapped three different forms of primary lymphedema inherited as autosomal dominants: primary congenital (PCL), onset with puberty (POL, the most common), and the rare lymphedema-distichiasis syndrome (LDS) in which there is hyperplasia of lymphatics, aplasia or hypoplasia of thoracic duct, and frequent cardiac malformations, in association with double row of eyelashes (distichiasis). The primary congenital lymphedema, mapped to 5q35.3, was recently shown by a group of investigators from Finland to be due in some families to missense mutations in the cytoplasmic tyrosine kinase domain of the vegfr3 gene.
The specific aims of this proposal are two fold: 1) to investigate the genetic linkage relationship of 113 families to 3 sites of PCL, LDS and POL as well as other locations that may become available during the course of this study and, to determine the genetic contribution of each lymphedema locus to the overall presentation of this phenotype; and 2) to search for mutation in a number of POL (and/or PCL) candidate genes and eventually to identify, clone, isolate and characterize the putative lymphedema genes. Depending on these results, they may embark on another round of a genome-wide search at 5-cM intervals in order to identify the chromosomal location of as yet unknown other POL loci.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL066150-01
Application #
6228506
Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Goldman, Stephen
Project Start
2001-08-20
Project End
2004-07-31
Budget Start
2001-08-20
Budget End
2002-07-31
Support Year
1
Fiscal Year
2001
Total Cost
$313,167
Indirect Cost
Name
University of Connecticut
Department
Surgery
Type
Schools of Medicine
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030
Rezaie, Tayebeh; Ghoroghchian, Rose; Bell, Rachel et al. (2008) Primary non-syndromic lymphoedema (Meige disease) is not caused by mutations in FOXC2. Eur J Hum Genet 16:300-4
Brice, G; Child, A H; Evans, A et al. (2005) Milroy disease and the VEGFR-3 mutation phenotype. J Med Genet 42:98-102
Evans, A L; Bell, R; Brice, G et al. (2003) Identification of eight novel VEGFR-3 mutations in families with primary congenital lymphoedema. J Med Genet 40:697-703