The type of variants at the COL3A1 gene associates with the phenotype and severity of vascular Ehlers-Danlos syndrome.

Published on Dec 1, 2015in European Journal of Human Genetics3.65
· DOI :10.1038/ejhg.2015.32
Michael Frank13
Estimated H-index: 13
(French Institute of Health and Medical Research),
Juliette Albuisson11
Estimated H-index: 11
(Paris V: Paris Descartes University)
+ 12 AuthorsXavier Jeunemaitre69
Estimated H-index: 69
(Paris V: Paris Descartes University)
The type of variants at the COL3A1 gene associates with the phenotype and severity of vascular Ehlers–Danlos syndrome
  • References (20)
  • Citations (51)
📖 Papers frequently viewed together
76 Citations
857 Citations
201059.10The Lancet
16 Authors (K.T. Ong, ..., Pierre Boutouyrie)
199 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Sherene Shalhub (UW: University of Washington)H-Index: 13
#2James Hamilton Black (Johns Hopkins University)H-Index: 27
Last. Nazli B. McDonnell (NIH: National Institutes of Health)H-Index: 16
view all 8 authors...
Objective The management of arterial pathology in individuals with vascular Ehlers-Danlos syndrome (vEDS) remains a challenge. Here we describe the correlation between COL3A1 gene mutation type and the clinical phenotype in individuals with vEDS. Methods Individuals with confirmed molecular diagnoses of vEDS were enrolled in a multi-institutional natural history study. Data collected included demographics, clinical and family histories, arterial pathology (aneurysm, dissection, and rupture), ope...
37 CitationsSource
#1Melanie G. Pepin (UW: University of Washington)H-Index: 23
#2Ulrike Schwarze (UW: University of Washington)H-Index: 30
Last. Peter H. Byers (UW: University of Washington)H-Index: 70
view all 6 authors...
76 CitationsSource
#1Kazunori Mizuno (Shriners Hospitals for Children - Portland)H-Index: 19
#2Sergei P. Boudko (OHSU: Oregon Health & Science University)H-Index: 20
Last. Hans Peter Bächinger (OHSU: Oregon Health & Science University)H-Index: 53
view all 4 authors...
Vascular Ehlers-Danlos syndrome (EDS) type IV is the most severe form of EDS. In many cases the disease is caused by a point mutation of Gly in type III collagen. A slower folding of the collagen helix is a potential cause for over-modifications. However, little is known about the rate of folding of type III collagen in patients with EDS. To understand the molecular mechanism of the effect of mutations, a system was developed for bacterial production of homotrimeric model polypeptides. The C-ter...
13 CitationsSource
#2Michael FrankH-Index: 13
Last. Benjamin FournierH-Index: 10
view all 11 authors...
Objective Vascular Ehlers–Danlos syndrome (vEDS) is a rare genetic condition related to mutations in the COL3A1 gene, responsible of vascular, digestive and uterine accidents. Difficulty of clinical diagnosis has led to the design of diagnostic criteria, summarised in the Villefranche classification. The goal was to assess oral features of vEDS. Gingival recession is the only oral sign recognised as a minor diagnostic criterion. The authors aimed to check this assumption since bibliographical se...
13 CitationsSource
#1Dru F. Leistritz (UW: University of Washington)H-Index: 10
#2Melanie G. Pepin (UW: University of Washington)H-Index: 23
Last. Peter H. Byers (UW: University of Washington)H-Index: 70
view all 4 authors...
Purpose: To characterize the clinical outcome of heterozygosity for COL3A1 null mutations in Ehlers-Danlos syndrome type IV, the vascular type. Methods: We identified mutations that produced premature termination codons and resulted in nonsense-mediated messenger RNA decay in 19 families. We reviewed the clinical and family histories and medical complications in 54 individuals from these families with COL3A1 null mutations. Results: Compared with individuals with missense or exon-skipping mutati...
60 CitationsSource
#1Laurence FaivreH-Index: 15
#2Gwenaëlle Collod-Béroud (University of Montpellier)H-Index: 29
Last. Guillaume JondeauH-Index: 52
view all 27 authors...
Mutations in the FBN1 gene cause Marfan syndrome (MFS) and have been associated with a wide range of milder overlapping phenotypes. A proportion of patients carrying a FBN1 mutation does not meet diagnostic criteria for MFS, and are diagnosed with "other type I fibrillinopathy." In order to better describe this entity, we analyzed a subgroup of 146 out of 689 adult propositi with incomplete "clinical" international criteria (Ghent nosology) from a large collaborative international study includin...
38 CitationsSource
#1Anton V. Persikov (UMDNJ: University of Medicine and Dentistry of New Jersey)H-Index: 19
#2Rian J. Pillitteri (UMDNJ: University of Medicine and Dentistry of New Jersey)H-Index: 1
Last. Barbara Brodsky (UMDNJ: University of Medicine and Dentistry of New Jersey)H-Index: 47
view all 6 authors...
A missense mutation leading to the replacement of one Gly in the (Gly-Xaa-Yaa)n repeat of the collagen triple helix can cause a range of heritable connective tissue disorders that depend on the gene in which the mutation occurs. Osteogenesis imperfecta results from mutations in type I collagen, Ehlers-Danlos syndrome type IV from mutations in type III collagen, Alport syndrome from mutations in type IV collagen, and dystrophic epidermolysis bullosa from mutations in type VII collagen. The predic...
65 CitationsSource
#1Ulrike Schwarze (UW: University of Washington)H-Index: 30
#2Wouter I. Schievink (UCI: University of California, Irvine)H-Index: 5
Last. Peter H. Byers (UW: University of Washington)H-Index: 70
view all 8 authors...
Mutations in the COL3A1 gene that encodes the chains of type III procollagen result in the vascular form of Ehlers-Danlos syndrome (EDS), EDS type IV, if they alter the sequence in the triple-helical domain. Although other fibrillar collagen–gene mutations that lead to allele instability or failure to incorporate proα-chains into trimers—and that thus reduce the amount of mature molecules produced—result in clinically apparent phenotypes, no such mutations have been identified in COL3A1. Further...
116 CitationsSource
#1Cecilia Giunta (Boston Children's Hospital)H-Index: 27
#2Beat Steinmann (Boston Children's Hospital)H-Index: 51
We report on 12 patients with EDS IV in whom clinical diagnosis was confirmed by biochemical analysis of collagen type III, and further proven by mutation analysis of the COL3A1 gene. Four overlapping RT-PCR products covering the coding sequence for the triple-helical domain of type III collagen were analyzed by direct sequencing. So far, we have identified, 4 base changes at donor splice junctions, and 1 base change at an acceptor splice site, which all affect mRNA splicing; 1 genomic deletion,...
25 CitationsSource
Mutations resulting in replacement of one obligate Gly residue within the repeating (Gly-Xaa-Yaa)(n) triplet pattern of the collagen type I triple helix are the major cause of osteogenesis imperfecta (OI). Phenotypes of OI involve fragile bones and range from mild to perinatal lethal. In this study, host-guest triple-helical peptides of the form acetyl-(Gly-Pro-Hyp)(3)-Zaa-Pro-Hyp-(Gly-Pro-Hyp)(4)-Gly-Gly-amide are used to isolate the influence of the residue replacing Gly on triple-helix stabil...
125 CitationsSource
Cited By51
#1Javier Barallobre-Barreiro ('KCL': King's College London)H-Index: 15
#2Bart Loeys (Radboud University Nijmegen)H-Index: 56
Last. Jason C. Kovacic (VCCRI: Victor Chang Cardiac Research Institute)H-Index: 34
view all 6 authors...
Highlights •The middle arterial layer, the tunica media, is composed of circumferentially arranged layers of VSMCs that are separated by concentrically arranged elastic lamellae, a form of ECM. •Advances in genetics and proteomics approaches have facilitated dramatic progress in our understanding of the key role of the ECM in vascular health and disease. •The emerging discoveries regarding the role of ECM in the vasculature hold promise to be developed into novel clinical disease biomarkers and ...
#1Mary B. CallaghanH-Index: 1
#2Rob Hadden (Derriford Hospital)H-Index: 1
Last. Peter D. TurnpennyH-Index: 32
view all 6 authors...
Familial amniotic band sequence (ABS) is rare but has been reported in the offspring of mothers with connective tissue disorders. We present a family of two half-siblings with ABS who share the same biological father. Following a serious vascular event a de novo pathogenic variant in COL3A1 was detected in the father, confirming a diagnosis of vascular Ehlers-Danlos syndrome (vEDS). The same variant was found in both his ABS-affected children but not in his unaffected child. The amniotic membran...
1 CitationsSource
#1Pierre Boutouyrie (University of Paris)H-Index: 4
Summary Vascular Ehlers-Danlos syndrome (OMIM 130050, 1/150 000 birth) is caused by mutations in Collagen 3A1 gene. It is associated with severe phenotype associating early arterial dissection and rupture, digestive and uterine perforations, and skin and joints fragility. Until recently, no treatment was available. Celiprolol, a beta1 antagonist with beta2 partial antagonist properties betablocker was tested in a randomized, controlled trial. We could show that this compound was associated with ...
#1Salma Adham (University of Paris)
#1Salma AdhamH-Index: 1
Last. Anne Legrand (French Institute of Health and Medical Research)H-Index: 2
view all 6 authors...
#1Marco Ritelli (University of Brescia)H-Index: 16
#2Chiara RovatiH-Index: 1
Last. Marina Colombi (University of Brescia)H-Index: 20
view all 7 authors...
Vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder due to heterozygous pathogenic COL3A1 variants. Arterial, intestinal, and/or uterine fragility is the disease hallmark and results in reduced life expectancy. The clinical diagnosis is not always straightforward and patients' selection for molecular confirmation depends on the characteristics of applied criteria, that is, the Villefranche criteria (in use until 2017) and their revision according to the new EDS ...
#1Nicolai P. OstbergH-Index: 1
#2Mohammad A. ZafarH-Index: 6
view all 4 authors...
Thoracic aortic aneurysm and dissection (TAAD) affects many patients globally and has high mortality rates if undetected. Once thought to be solely a degenerative disease that afflicted the aorta due to high pressure and biomechanical stress, extensive investigation of the heritability and natural history of TAAD has shown a clear genetic basis for the disease. Here, we review both the cellular mechanisms and clinical manifestations of syndromic and non-syndromic TAAD. We particularly focus on g...
1 CitationsSource
#2Salma Adham (Paris V: Paris Descartes University)H-Index: 1
Last. Xavier Jeunemaitre (Paris V: Paris Descartes University)H-Index: 69
view all 6 authors...
Vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited disorder leading to arterial, digestive, and uterine complications due to pathogenic COL3A1 variants. Identification of causal variants allows family screening, provided that relatives have previously been informed, according to a 2013 French Decree. The aims of our study were to assess the communication of genetic information to at-risk relatives, the impact of diagnosis disclosure and to highlight a possible link between the experience...
#1Sherene Shalhub (UW: University of Washington)H-Index: 13
#2Peter H. Byers (UW: University of Washington)H-Index: 70
Last. Karen Woo (UCLA: University of California, Los Angeles)H-Index: 10
view all 24 authors...
Abstract Objective Vascular Ehlers-Danlos syndrome (vEDS) is a rare disorder and 1 of 13 types of EDS. The syndrome results in aortic and arterial aneurysms and dissections at a young age. Diagnosis is confirmed with molecular testing via skin biopsy or genetic testing for COL3A1 pathogenic variants. We describe a multi-institutional experience in the diagnosis of vEDS from 2000 to 2015. Methods This is a multi-institutional cross-sectional retrospective study of individuals with vEDS. The insti...
#1G. Goudot (Paris V: Paris Descartes University)H-Index: 1
#2Clement Papadacci (PSL Research University)H-Index: 9
Last. Tristan Mirault (Paris V: Paris Descartes University)H-Index: 14
view all 11 authors...
Objective Vascular Ehlers–Danlos syndrome (vEDS) is associated with arterial ruptures due to a mutant gene encoding collagen type III (Col-III). To better understand the role of Col-III, we aimed at evaluating aortic stiffness and dynamic stiffening in vEDS mouse models, with either a quantitative (col3KO mice) or a qualitative Col-III defect (col3KI mice). Materials and Methods Abdominal aortic wall pulse wave velocities (PWV) in col3KO and col3KI mice were compared to their respective wild typ...
2 CitationsSource