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Clinical and Genetic Features of Ehlers–Danlos Syndrome Type IV, the Vascular Type

Published on Mar 9, 2000in The New England Journal of Medicine70.67
· DOI :10.1056/NEJM200003093421001
Melanie G. Pepin23
Estimated H-index: 23
(UW: University of Washington),
Ulrike Schwarze30
Estimated H-index: 30
(UW: University of Washington)
+ 1 AuthorsPeter H. Byers70
Estimated H-index: 70
(UW: University of Washington)
Abstract
Background Ehlers–Danlos syndrome type IV, the vascular type, results from mutations in the gene for type III procollagen (COL3A1). Affected patients are at risk for arterial, bowel, and uterine rupture, but the timing of these events, their frequency, and the course of the disease are not well documented. Methods We reviewed the clinical and family histories of and medical and surgical complications in 220 index patients with biochemically confirmed Ehlers–Danlos syndrome type IV and 199 of their affected relatives. We identified the underlying COL3A1 mutation in 135 index patients. Results Complications were rare in childhood; 25 percent of the index patients had a first complication by the age of 20 years, and more than 80 percent had had at least one complication by the age of 40. The calculated median survival of the entire cohort was 48 years. Most deaths resulted from arterial rupture. Bowel rupture, which often involved the sigmoid colon, accounted for about a quarter of complications but rarely l...
  • References (29)
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References29
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#1Joseph SambrookH-Index: 31
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Molecular Cloning has served as the foundation of technical expertise in labs worldwide for 30 years. No other manual has been so popular, or so influential. Molecular Cloning, Fourth Edition, by the celebrated founding author Joe Sambrook and new co-author, the distinguished HHMI investigator Michael Green, preserves the highly praised detail and clarity of previous editions and includes specific chapters and protocols commissioned for the book from expert practitioners at Yale, U Mass, Rockefe...
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#2Ulrike Schwarze (UW: University of Washington)H-Index: 30
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Ehlers-Danlos syndrome (EDS) type IV is an autosomal dominant connective tissue disorder. Early morbidity and mortality results from rupture of vessels and internal organs. A large kindred with EDS type IV was studied clinically, and the biochemical defects and underlying mutation in the COL3A1 gene that encodes the chains of type III procollagen were identified. A GA transition results in a single amino acid substitution, G571S, in the triple helical domain of the products of one COL3A1 allele....
23 CitationsSource
#1Peter Beighton (UCT: University of Cape Town)H-Index: 51
#2A. De PaepeH-Index: 81
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Categorization of the Ehlers-Danlos syndromes began in the late 1960s and was formalized in the Berlin nosology. Over time, it became apparent that the diagnostic criteria established and published in 1988 did not discriminate adequately between the different types of Ehlers-Danlos syndromes or between Ehlers-Danlos syndromes and other phenotypically related conditions. In addition, elucidation of the molecular basis of several Ehlers-Danlos syndromes has added a new dimension to the characteriz...
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The collagens are a large and diverse family of proteins which are found in the extracellular matrix. In common with one another, the 19 known collagen types have triple-helical domains of variable length but they differ with respect to their overall size and the nature and location of their globular domains. Collagen mutations lead to heritable defects of connective tissues and mutation data for collagen types I and III are presented here. The mutation data are accessible on the world wide web ...
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Summary Ehlers-Danlos syndrome (EDS) type IV results from mutations in the COL3A1 gene, which encodes the constituent chains of type III procollagen. We have identified, in 33 unrelated individuals or families with EDS type IV, mutations that affect splicing, of which 30 are point mutations at splice junctions and 3 are small deletions that remove splice-junction sequences and partial exon sequences. Except for one point mutation at a donor site, which leads to partial intron inclusion, and a si...
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Summary We have recently analysed by hislological, protein and molecular DNA techniques 23 mutations of the collagen III gene (COL3AI). most of which cause premature arterial fragility, thin skin and variants of vascular Ehlers-Danlos syndrome. There were 14 glycinesubstitutions between residues 637 and 1021. eight exon skips between exons 7 and 45 and one small inframe deletion. The glycine substitutions produce a gradient of increasingly abnormal clinical phenotypes from exons 36 to 49 while t...
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