Mutations in FOXC2 Are Strongly Associated With Primary Valve Failure in Veins of the Lower Limb
- 10 April 2007
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 115 (14), 1912-1920
- https://doi.org/10.1161/circulationaha.106.675348
Abstract
Background— Mutations in the FOXC2 gene cause lymphedema distichiasis, an inherited primary lymphedema in which a significant number of patients have varicose veins. Because lymphedema distichiasis is believed to be caused by lymphatic valve failure (reflux), and FOXC2 is highly expressed on venous valves in mouse embryos, we tested the hypothesis that FOXC2 mutations may be linked to venous valve failure and reflux. Methods and Results— The venous system of the leg was investigated with Duplex ultrasound. Pathological reflux was recorded by color Duplex ultrasound in all 18 participants with a FOXC2 mutation, including 3 without lymphedema. Every participant with a mutation in FOXC2 showed reflux in the great saphenous vein (n=18), compared with only 1 of 12 referents (including 10 family members; P Conclusions— FOXC2 is the first gene in which mutations have been strongly associated with primary venous valve failure in both the superficial and deep veins in the lower limb. This gene appears to be important for the normal development and maintenance of venous and lymphatic valves.Keywords
This publication has 31 references indexed in Scilit:
- Linkage to the FOXC2 region of chromosome 16 for varicose veins in otherwise healthy, unselected sibling pairsJournal of Medical Genetics, 2005
- The Venous RefluxAngiology, 2004
- Heritability of Venous Function in HumansArteriosclerosis, Thrombosis, and Vascular Biology, 2004
- FOXC2 haploinsufficient mice are a model for human autosomal dominant lymphedema-distichiasis syndromeHuman Molecular Genetics, 2003
- Lifestyle factors and the risk of varicose veins Edinburgh Vein StudyJournal of Clinical Epidemiology, 2003
- The murine winged helix transcription factors, Foxc1 and Foxc2, are both required for cardiovascular development and somitogenesisGenes & Development, 2001
- Analysis of lymphoedema-distichiasis families forFOXC2 mutations reveals small insertions and deletions throughout the geneHuman Genetics, 2001
- Mutations in FOXC2 (MFH-1), a Forkhead Family Transcription Factor, Are Responsible for the Hereditary Lymphedema-Distichiasis SyndromeAmerican Journal of Human Genetics, 2000
- Prevalence of varicose veins and chronic venous insufficiency in men and women in the general population: Edinburgh Vein StudyJournal of Epidemiology and Community Health, 1999
- Importance of the Familial Factor in Varicose DiseaseThe Journal of Dermatologic Surgery and Oncology, 1994