Task: Question Answering
Input (English): Context: The Ehlers-Danlos syndromes (EDS) are a heterogeneous group of heritable connective tissue disorders characterised by joint hypermobility, involvement of skin and tissue fragility. The Villefranche criteria have simplified its diagnosis, which, however, remains difficult in children and young adults with vascular and hypermobile EDS as well as in patients without a positive family history. Diagnosis of vascular EDS is important for clinical follow-up, genetic counseling and prenatal diagnosis. We describe the biochemical and molecular-genetic diagnosis of vascular EDS. We describe five families with vascular EDS. Analysis of (pro)collagens obtained from cultured fibroblasts was done using SDS-PAGE. The structure and amounts of (pro)collagen I, III and V were determined by autoradioflourography. This was also done in 362 controls or patients without a diagnosis of vascular EDS. Molecular testing was done in Professor Anne de Paepe's laboratory in Belgium by sequencing of COL3A1. (Pro)collagen from all five patients with vascular EDS was abnormal by SDS-PAGE: intracellular retention, reduced secretion and overmodification of the a1 chains of (pro)collagen III. Molecular analysis revealed an abnormality of COL3A1 in all patients. Abnormalities of (pro)collagen III were not observed in patients without a diagnosis of vascular EDS. Among 90 patients with non-vascular EDS, one patient had an abnormality of collagen I. Biochemical analysis of (pro)collagen obtained from cultured fibroblasts is a good screening procedure for vascular EDS, but it is of limited value in non-vascular EDS. Molecular testing will disclose an abnormality of COL3A1 in many patients with abnormal (pro)collagen III on SDS-PAGE. The findings make precise genetic counselling and prenatal diagnosis possible in families with vascular EDS. 
 Question: What tissue is most affected in Ehlers-Danlos syndromes?
Output (English): connective tissue