GENETIC-LINKAGE TO THE COLLAGEN ALPHA-1(V) GENE (COL5A1) IN 2 BRITISHEHLERS-DANLOS-SYNDROME FAMILIES WITH VARIABLE TYPE-I AND TYPE-II PHENOTYPES

To investigate the role of COL5A1 as a candidate gene for Ehlers-Danlo s syndrome (EDS), we have carried out linkage studies in two large Bri tish families with EDS type I/II and type II, respectively. Fourteen l iving, affected individuals were identified by family-history clinical examination and ultrastructural analysis. a polymorphic intragenic si mple sequence repeat at the COL5A1 locus showed linkage to EDS without recombination to give a combined lod score of 5.7. We have previously reported linkage to COL5A1 in an EDS type I/II family which brings th e total lod score to 9.8 at zero recombination. Taken together, these data implicate COL5A1 as an important cause of EDS and confirm that ty pes I and II are allelic.