Vascular Ehlers-Danlos syndrome (vEDS) is a rare and severe autosomal dominant disorder caused by variants at the COL3A1 gene. Clinical characteristics and course of disease of 215 molecularly proven patients (146 index cases and 69 relatives) were analysed. We found 126 distincts variants that were divided into five groups: (1) Glycine substitutions (n = 71), (2) splice-site and in-frame insertions-deletions (n = 36), (3) variants leading to haplo-insufficiency (n = 7), (4) non-glycine missense variants within the triple helix (n = 4 variants), and (5) non-glycine missense variants or in-frame insertions-deletions, in the N-or C-terminal part of the protein (n = 8). Overall, our cohort confirmed the severity of the disease with a median age at first complication of 29 years (IQR 22-39), the most frequent being arterial (48%) and digestive (24%) ruptures. Groups 2 and 1 were significantly more severe than groups 3-5, with extreme median ages at first major complication of 23-47 years. Patients of groups 3-5 had a less typical phenotype and remarkably absence of digestive events. The distribution of glycine-replacing amino acids was strongly biased towards more destabilizing residues of the collagen assembly. Thus the natural course of vEDS and the clinical phenotype of patients are influenced by the type of COL3A1 variant. This study also confirms that patients with variants located in the C-and N-termini or leading to haplo-insufficiency have milder course of the disease and less prevalent diagnostic criteria. These findings may help refine diagnostic strategy, genetic counselling and clinical care.

Abstract-Previous reports have investigated associations between carotid intima-media thickness (IMT) and cardiovascular risk factors. Our objective was to investigate this question in greater depth by measuring both femoral and carotid IMT in relation to sex and multifactorial coronary risk. We investigated carotid and femoral artery IMT by using ultrasonography in 326 men and 462 women, 17 to 65 years old. We also evaluated body mass index, blood pressure, blood lipids, glucose, smoking, and Framingham coronary risk. In both vessels, IMT was lower in women than in men. Significant relations between carotid and femoral IMT existed with age and most risk factors in both sexes. After adjustment for age, carotid IMT was related to risk factors in both sexes except for diastolic blood pressure, HDL cholesterol, and smoking in women, whereas femoral IMT was related to triglycerides and smoking in both sexes, systolic blood pressure and blood glucose in men, and total and HDL cholesterol in women. Significant unadjusted and age-adjusted relations of Framingham risk existed with carotid and femoral IMT in both sexes, but slopes of these relations were greater (1) before than after age adjustment, (2) in men than in women at both sites, except the femoral artery after age adjustment, and (3) at the carotid than at the femoral site in both sexes before age adjustment. Carotid IMT in men appears to be a more powerful predictor than it is in women and femoral IMT in both sexes in reflecting multifactorial coronary risk burden, but these differences are partly conditional on age. (Arterioscler Thromb Vasc Biol. 1998;18:584-590.)Key Words: arteries Ⅲ risk factors Ⅲ coronary disease Ⅲ atherosclerosis Ⅲ ultrasound T he early detection of preclinical arterial disease may increase our ability to predict the subsequent risk of cardiovascular complications and lead to optimal disease prevention strategies.1,2 There is growing evidence that the thickening of the arterial wall observable with B-mode ultrasonography represents one initial step of preclinical arterial disease.3 Even in the absence of discrete plaque, the combined thickness of the arterial intima and media, the so-called IMT, can be measured with considerable precision, particularly by coupling high-resolution, B-mode ultrasonography with an automated, computerized system of image analysis. [4][5][6] Several studies of selected patients at risk for cardiovascular disease and a few population-based studies have provided evidence of an association between IMT, as measured in the extracranial carotid arteries, and cardiovascular risk factors. 3,4,[7][8][9][10][11][12] However, little attention has been given to the influence of risk factors on IMT as measured at sites other than the carotid artery, such as the femoral, 8 -13 a vessel considered to be as prone to atherogenesis as the carotid.14 The AXA Study is a prospective, worksite study designed to investigate the influence over time of traditional and new risk factors 15,16 on carotid and femoral IMT as assessed ultr...