title: Ehlers-Danlos syndrome type VII: phenotype and genotype.
abstract: A patient suffering from a severe form of Ehlers-Danlos syndrome is presented (EDS type VII). The presence of bilateral congenital hip dislocation, generalized joint hypermobility and a soft hyperelastic skin with abnormal scarring suggested a specific collagen type I defect. SDS-PAGE analysis of collagens secreted into the medium of fibroblast cultures showed a retarded migration of more than half of the alpha 2(I) chains. CNBr peptide mapping of the HPLC-purified altered chain localized the mutant locus to the N-terminal region of the protein. cDNA analysis of the corresponding gene COL1A2 revealed, in addition to the expected 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 nucleotide of intron 6.
authors.affiliation: Institute of Medical Molecular Biology, Medical University of Lübeck, Germany.
authors.forename: H W
authors.initials: HW
authors.lastname: Lehmann
authors.forename: S
authors.initials: S
authors.lastname: Mundlos
authors.forename: A
authors.initials: A
authors.lastname: Winterpacht
authors.forename: R E
authors.initials: RE
authors.lastname: Brenner
authors.forename: B
authors.initials: B
authors.lastname: Zabel
authors.forename: P K
authors.initials: PK
authors.lastname: Müller
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D003094:Collagen / Q000032:analysis / Q000235:genetics*; D004535:Ehlers-Danlos Syndrome / Q000235:genetics*; D005091:Exons; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype
chemical_list: D003094:Collagen