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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
Author(s) -
McGrory J.,
Weksberg R.,
Thorner P.,
Cole W. G.
Publication year - 1996
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.1996.tb02709.x
Subject(s) - extracellular matrix , glycine , triple helix , chemistry , collagen, type i, alpha 1 , fibril , type i collagen , dermis , fibroblast , glutamic acid , procollagen peptidase , endoplasmic reticulum , microbiology and biotechnology , biochemistry , amino acid , biology , endocrinology , anatomy , in vitro , stereochemistry
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 α 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 α 1(III) chains. The dermal collagen fibrils were narrow, but their constituent type III collagen molecules contained predominantly normal α 1(III) chains. As a result, 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.