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Multiple Defects in Type III Collagen Synthesis Are Associated with the Pathogenesis of Abdominal Aortic Aneurysms a
Author(s) -
ANDERSON DAVID W.,
EDWARDS TROY K.,
RICKETTS MICHAEL H.,
KUIVANIEMI HELENA,
TROMP GERARD,
STOLLE CATHERINE A.,
DEAK SUSAN B.,
BOYD CHARLES D.
Publication year - 1996
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1996.tb33312.x
Subject(s) - type i collagen , collagen, type i, alpha 1 , fibroblast , pathogenesis , proband , abdominal aortic aneurysm , medicine , microbiology and biotechnology , biology , mutation , endocrinology , pathology , aneurysm , gene , biochemistry , surgery , in vitro , extracellular matrix
Confluent skin fibroblast cultures were prepared from 40 patients diagnosed with and surgically treated for an abdominal aortic aneurysm. An analysis of secreted type I and type III collagen in the media of these fibroblast preparations revealed reduced secretion of type III collagen from six patients. DNA sequence analysis of the entire coding domain of the pro alpha 1 (III) collagen mRNA in skin fibroblast RNA from these six patients revealed a C to T substitution at nucleotide 607 in one of the probands that would result in the replacement of a leucine residue with phenylalanine in the second position of the first tripeptide repeat in the triple-helical domain of type III collagen. Allele-specific hybridization analysis of genomic DNA from this proband and family members indicated that this non-glycine substitution probably contributed to the aneurysmal phenotype in this patient. No coding sequence mutations were found in the other five patients. It is clear from this study, therefore, that aberrant synthesis of type III collagen, as a consequence of both a coding sequence mutation and other factors contributing to reduced secretion of type III procollagen, will result in the development of an aortic aneurysm in a significant percentage of patients with this disease.