J. Yang, W. Chen, J. Tran, N.B. McDonnell, C.A. Francomano
Presented at the annual meeting of The American Society of Human Genetics, October 12, 2006, New Orleans, Louisiana.

ABSTRACT
Vascular Ehlers-Danlos Syndrome (VEDS) is a rare genetic disorder affecting approximately 1 in 100,000 individuals, resulting from mutations in the gene for type III procollagen (COL3A1). Affected patients are at risk for arterial, bowel, and uterine rupture and have a significantly reduced life expectancy. We describe a pedigree in which a single base pair substitution leading to a G786R mutation in Col3A1 was detected in a 55-year-old proband and her 30-year-old son. Previously performed protein gel electrophoresis analysis on a clinical basis found abnormal type III procollagen motility. A review of the family history revealed that at least 10 additional members of the family are affected with VEDS. A total of 6 premature deaths (age range 14-55) were reported due to aneurysms and bleeding complications. However, there was no history of uterine rupture or pregnancy- related death in five affected females with a total of ten pregnancies. A vascular work-up including MRI/MRA imaging and echocardiography in the 30-year-old son who carries the G786R mutation was completed and did not reveal any abnormalities. A review of the clinical history in affected family members revealed variability in the facial characteristics as well as musculoskeletal features of the disorder, in addition to the vascular presentation. The phenotypic variability speaks to the role of environmental interactions as well as possible influence of modifier loci. The study of modifying influences may lead to the identification of therapeutic approaches to reduce the complications of VEDS.