EHLERS-DANLOS SYNDROME TYPE-VII - PHENOTYPE AND GENOTYPE

A patient suffering from a severe form of Ehlers-Danlos syndrome is pr esented (EDS type VII). The presence of bilateral congenital hip dislo cation, generalized joint hypermobility and a soft hyperelastic skin w ith abnormal scarring suggested a specific collagen type I defect. SDS -PAGE analysis of collagens secreted into the medium of fibroblast cul tures showed a retarded migration of more than half of the alpha 2(I) chains. CNBr peptide mapping of the HPLC-purified altered chain locali zed the mutant locus to the N-terminal region of the protein. cDNA ana lysis of the corresponding gene COL1A2 revealed, in addition to the ex pected collagen sequence, a transcript missing the entire exon 6. This exon encodes a major crosslinking site within collagen fibres as well as the N-propeptidase cleavage site. The skipping of exon 6 is caused by a splice site mutation substituting an A for a G at the first nucl eotide of intron 6.