Segregation analysis of the structural genes of the major fibrillar collagens provides further evidence of molecular heterogeneity in type II Ehlers-Danlos syndrome.

Type II Ehlers-Danlos syndrome (EDS) is one of a group of disorders characterized by striking abnormalities of the soft connective tissues. The major fibrillar collagens (types I and III) found in these tissues have important stress-bearing functions and abnormal collagen could therefore account for the clinical features of this condition. We have used a number of restriction site dimorphisms, tightly linked to the structural genes of type I collagen (COL1A1 COL1A2) and type III collagen (COL3A1), to investigate the segregation of corresponding alleles in three pedigrees in which type II EDS was clearly inherited as a dominant trait. Discordant segregation of all three collagen genes was seen in a large pedigree that included 17 affected individuals with the typical phenotype of type II EDS. Thus mutations in neither type I nor type III collagen genes were responsible for the disease in this family. In a second small pedigree discordant segregation of the disease with both type I collagen loci was observed while the concordant segregation seen at COL3A1 could easily have arisen by chance (P = 0.5). The third pedigree was uninformative at all three collagen loci because of inability to discriminate between the parental alleles. These results suggest that there may be molecular heterogeneity of type II EDS since abnormalities of type I collagen have been described in other individuals phenotypically similar to those in our study.