title: Detection and characterisation of an overmodified type III collagen by analysis of non-cutaneous connective tissues in a patient with Ehlers-Danlos syndrome IV.
abstract: The clinical and biochemical observations in a patient with a mild form of Ehlers-Danlos syndrome (EDS) type IV are described. The patient's skin fibroblasts produced markedly diminished amounts of type III collagen. SDS-polyacrylamide gel electrophoresis of collagens produced by cells obtained from other, non-cutaneous tissues showed two forms of collagen alpha 1(III) chains, a normal and a slow migrating, mutant form. Further analysis confirmed that the type III collagen molecules containing mutant alpha chains which were overmodified had a lower thermal stability and were poorly secreted into the extracellular medium. The protein defect was mapped by in situ cyanogen bromide digestion and was located in alpha 1(III) CB9, the C-terminal peptide of the collagen triple helix. This study shows that non-cutaneous connective tissues can be a useful source for the study of type III collagen defects in patients with EDS type IV.
authors.affiliation: Centre for Medical Genetics, University of Gent, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Nuytinck
authors.forename: P
authors.initials: P
authors.lastname: Narcisi
authors.forename: A
authors.initials: A
authors.lastname: Nicholls
authors.forename: J P
authors.initials: JP
authors.lastname: Renard
authors.forename: F M
authors.initials: FM
authors.lastname: Pope
authors.forename: A
authors.initials: A
authors.lastname: De Paepe
mesh_terms: D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics* / Q000378:metabolism; D003238:Connective Tissue / Q000378:metabolism* / Q000473:pathology; D003488:Cyanogen Bromide; D004535:Ehlers-Danlos Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010449:Peptide Mapping; D011233:Precipitin Tests; D011347:Procollagen / Q000378:metabolism; D012333:RNA, Messenger / Q000302:isolation & purification
chemical_list: D011347:Procollagen; D012333:RNA, Messenger; D003094:Collagen; D003488:Cyanogen Bromide