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.