title: Abnormal extracellular matrix in Ehlers-Danlos syndrome type IV due to the substitution of glycine 934 by glutamic acid in the triple helical domain of type III collagen.
abstract: A unique substitution of glycine 934 by glutamic acid in the triple helical domain of type III collagen was identified in a proband with Ehlers-Danlos syndrome type IV. The substitution was due to the transition of G 3302 to A in alpha 1(III) cDNA which is encoded by exon 46 of COL3A1. It resulted in a severe deficiency of type III collagen in fibroblast cultures and dermis. Dilatation of the endoplasmic reticulum of the dermal fibroblasts was probably due to the failure of these cells to secrete type III collagen molecules containing one or more mutant alpha 1(III) chains. The dermal collagen fibrils were narrow, but their constituent type III collagen molecules contained predominantly normal alpha 1(III) chains. As a results, the major effect of the substitution of glycine 934 by glutamic acid was to severely reduce the amount of normal type III collagen available for the formation of heterotypic collagen fibrils in the extracellular matrix.
authors.affiliation: Division of Orthopaedics, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: McGrory
authors.forename: R
authors.initials: R
authors.lastname: Weksberg
authors.forename: P
authors.initials: P
authors.lastname: Thorner
authors.forename: W G
authors.initials: WG
authors.lastname: Cole
mesh_terms: D000368:Aged; D003094:Collagen / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D004535:Ehlers-Danlos Syndrome / Q000235:genetics* / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012867:Skin / Q000473:pathology
chemical_list: D003094:Collagen