The gene encoding collagen alpha1(V)(COL5A1) is linked to mixed Ehlers-Danlos syndrome type I/II

The Ehlers-Danlos syndrome (EDS) is a heterogeneous group of inherited connective tissue disorders in which cutaneous fragility and ligamentous laxity often combine with vascular, gastrointestinal, and skeletal deformities. There is considerable phenotypic overlap between the more common forms of EDS (types I and II), in which specific molecular defects have not yet been identified. Recently, genetic linkage has been demonstrated between the COL5A1 gene, which encodes the alphal chain of type V collagen, and EDS type II in a large British kindred. Using a polymorphic intragenic simple sequence repeat at the COL5A1 locus, we now demonstrate tight linkage to EDS type I/II in a three-generation family, giving a LOD score (log10 of the odds for linkage) of 4.07 at zero recombination. The variation in expression in this family suggests that EDS types I and II are allelic, and the linkage data support the hypothesis that mutation in COL5A1 can cause both phenotypes.