Absence of apparent disease causing mutations in COL5A3 in 13 patients with hypermobility Ehlers-Danlos syndrome.

摘要

Collagen V is a minor fibrillar collagen, broadly distributed as al(V)2oc2(V) heterotrimers [Fessler and Fessler, 1987] that are incorporated into collagen I fibrils, and which regulate the shapes and diameters of collagen I/V heterotypic fibrils [Birk et al., 1988, 19901. Defects in the COL5A1 and COL5A2 genes underlie at least half of the cases of classic Ehlers-Danlos syndrome (EDS) [Toriello et al., 1996; Wenstrup et al., 1996; Michalickova et al., 1998; Richards et al., 1998; Schwarze et al., 2000; Malfait and De Paepe, 2005]. Collagen V is also found in the form of a relatively uncharacterized al(V)oc2(V)a3(V) heterotrimer, with a limited tissue distribution. Involvement of COL5A1 and COL5A2 defects in classic EDS, and expression of oc3(V) chains in joint capsule, skin [Brown et al., 1978], and developing ligaments [Imamura et al., 2000] suggested COL5A3 as a candidate locus for the most common form of EDS, the hypermobility type (h-EDS). A candidate locus has yet to be identified for the vast majority of h-EDS cases [Malfait et al., 2006]. Thus, we examined the COL5A3 locus and its products in 13 patients with h-EDS, identified using the previously specified diagnostic criteria [Beighton et al., 1998]. The features of the individual patients are described in Table I. This research was reviewed and approved by the ethics committee of the Hospital for Sick Children.