The Experts below are selected from a list of 912 Experts worldwide ranked by ideXlab platform
Mark T Keating - One of the best experts on this subject based on the ideXlab platform.
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elastin point mutations cause an obstructive vascular disease Supravalvular Aortic Stenosis
Human Molecular Genetics, 1997Co-Authors: Amanda E Toland, Colleen A Morris, Gregory J Ensing, Mark T Keating, Donald L Atkinson, Beth B BoakAbstract:Supravalvular Aortic Stenosis (SVAS) is an inherited obstructive vascular disease that affects the aorta, carotid, coronary and pulmonary arteries. Previous molecular genetic data have led to the hypothesis that SVAS results from mutations in the elastin gene, ELN. In these studies, the disease phenotype was linked to gross DNA rearrangements (35 and 85 kb deletions and a translocation) in three SVAS families. However, gross rearrangements of ELN have not been identified in most cases of autosomal dominant SVAS. To define the spectrum of ELN mutations responsible for this disorder, we refined the genomic structure of human ELN and used this information in mutational analyses. ELN point mutations co-segregate with the disease in four familial cases and are associated with SVAS in three sporadic cases. Two of the mutations are nonsense, one is a single base pair deletion and four are splice site mutations. In one sporadic case, the mutation arose de novo. These data demonstrate that point mutations of ELN cause autosomal dominant SVAS.
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genetic approaches to cardiovascular disease Supravalvular Aortic Stenosis williams syndrome and long qt syndrome
Circulation, 1995Co-Authors: Mark T KeatingAbstract:Background Although family history can be an important risk factor for cardiovascular disease, relatively little is known about the nature of specific genetic risk factors. One approach to this problem is to identify and characterize genes responsible for inherited disorders in the hope that this information will also provide mechanistic insight into common forms of cardiovascular disease. Methods and Results Over the last decade, it has become possible to identify genes that cause human disease by use of the techniques of molecular genetics, specifically genetic linkage analysis, positional cloning, and mutational analyses. We have used these techniques to study three inherited cardiovascular disorders: Supravalvular Aortic Stenosis, Williams syndrome, and long-QT syndrome. We have discovered that the vascular pathology of Supravalvular Aortic Stenosis and Williams syndrome results from mutations involving the elastin gene on chromosome 7q11.23. These mutations include intragenic deletions, translocation...
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Supravalvular Aortic Stenosis associated with a deletion disrupting the elastin gene
Journal of Clinical Investigation, 1994Co-Authors: Amanda K Ewart, Colleen A Morris, Donald L Atkinson, Weishan Jin, Mark T KeatingAbstract:Abstract Supravalvular Aortic Stenosis (SVAS) is an inherited vascular disease that can cause heart failure and death. SVAS can be inherited as an autosomal dominant trait or as part of a developmental disorder, Williams syndrome (WS). In recent studies we presented evidence suggesting that a translocation disrupting the elastin gene caused SVAS in one family while deletions involving the entire elastin locus caused WS. In this study, pulsed-field, PCR, and Southern analyses showed that a 100-kb deletion of the 3' end of the elastin gene cosegregated with the disease in another SVAS family. DNA sequence analysis localized the breakpoint between elastin exons 27 and 28, the same region disrupted by the SVAS-associated translocation. These data indicate that mutations in the elastin gene cause SVAS and suggest that elastin exons 28-36 may encode critical domains for vascular development.
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a human vascular disorder Supravalvular Aortic Stenosis maps to chromosome 7
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: Amanda K Ewart, Colleen A Morris, Gregory J Ensing, James Loker, Cynthia Moore, M Leppert, Mark T KeatingAbstract:The pathogenesis of vascular disease is unclear, but genetic factors play an important role. In this study we performed linkage analyses in two families with Supravalvular Aortic Stenosis, an inherited vascular disorder that causes narrowing of major arteries and may lead to cardiac overload and failure. DNA markers on the long arm of chromosome 7 (D7S371, D7S395, D7S448, and ELN) were linked to Supravalvular Aortic Stenosis in both families with a combined logarithm of likelihood for linkage (lod score) of 5.9 at the ELN locus. These findings indicate that a gene for Supravalvular Aortic Stenosis is located in the same chromosomal subunit as elastin, which becomes a candidate for the disease gene.
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the elastin gene is disrupted by a translocation associated with Supravalvular Aortic Stenosis
Cell, 1993Co-Authors: Mark E Curran, Amanda K Ewart, Colleen A Morris, M Leppert, Donald L Atkinson, Mark T KeatingAbstract:To identify genes involved in vascular disease, we investigated patients with Supravalvular Aortic Stenosis (SVAS), an inherited vascular disorder that causes hemodynamically significant narrowing of large elastic arteries. Pulsed-field gel and Southern analyses showed that a translocation near the elastin gene cosegregated with SVAS in one family. DNA sequence analyses demonstrated that the translocation disrupted the elastin gene and localized the breakpoint to exon 28. Taken together with our previous study linking SVAS to the elastin gene in two additional families and existing knowledge of vascular biology, these data suggest that mutations in the elastin gene can cause SVAS.
Bart Meyns - One of the best experts on this subject based on the ideXlab platform.
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early and late outcomes after surgical repair of congenital Supravalvular Aortic Stenosis a european congenital heart surgeons association multicentric study
European Journal of Cardio-Thoracic Surgery, 2017Co-Authors: Massimo A Padalino, David J Barron, Anna Chiara Frigo, M Comisso, Martin Kostolny, Ikenna Omeje, Christian Schreiber, Jelena Pabst Von Ohain, Julie Cleuziou, Bart MeynsAbstract:OBJECTIVES Our goal was to evaluate the early and late results of the surgical management of congenital Supravalvular Aortic Stenosis (SVAS). METHODS We performed a retrospective, multicentre study using data from the European Congenital Heart Surgeons Association. Exclusion criteria were age >18 years, operation before 1990 and redo Supravalvular Aortic Stenosis operations. Multivariate Cox regression analysis was performed to detect independent predictors of adverse events. RESULTS Of a total of 301 patients (male/female = 194/107; median age 3.9 years, range 13 days-17.9 years), 17.6% had a prior surgical or interventional procedure. Pulmonary artery Stenosis was present in 41.5% and coronary anomalies in 13.6%. The operation consisted of a single patch repair in 36.7%, a pantaloon-shaped patch in 36.7%, a 3-patch technique in 14.3% and other techniques in 11.7%. Postoperative complications occurred in 14.9%, and the early mortality rate was 5%. At a median follow-up of 13 years (interquartile range 3.5-7.8; follow-up completed 79.1%), there were 10 late deaths (4.2%). A surgical reoperation or an interventional cardiology procedure occurred in 12.6% and 7.2%, respectively. No significant differences in outcomes between the techniques were found. Age at repair <12 months and pulmonary artery Stenosis were associated with an increased risk of early (P = 0.0001) and overall mortality (P = 0.025), respectively. Having an operation after 2005 and co-existing pulmonary artery Stenosis were significant predictors of late reintervention (P = 0.0110 and P = 0.001, respectively). CONCLUSIONS Surgical repair of congenital Stenosis is an effective procedure with acceptable surgical risk and good late survival, but late morbidity is not negligible, especially in infants and when associated pulmonary artery Stenosis is present.
Stuart W Jamieson - One of the best experts on this subject based on the ideXlab platform.
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surgical management of congenital obstruction of the left main coronary artery with Supravalvular Aortic Stenosis
The Journal of Thoracic and Cardiovascular Surgery, 2000Co-Authors: Patricia A Thistlethwaite, Michael M Madani, Jolene M Kriett, Kirk Milhoan, Stuart W JamiesonAbstract:Abstract Objective: Stenosis of the left main coronary artery is a recognized complicating feature of Supravalvular Aortic Stenosis. We have retrospectively identified three anatomic subtypes of left main coronary obstruction in patients with Supravalvular Aortic Stenosis, each necessitating a distinct surgical approach. Methods: From 1991 to 1998, 9 patients underwent surgical repair of Supravalvular Aortic Stenosis and left main coronary Stenosis. Five patients (group 1) had obstruction from near-circumferential thickening of the left main ostium, 2 patients (group 2) had restricted coronary flow due to fusion of an Aortic valve leaflet to the Supravalvular ridge, and 2 patients (group 3) had diffuse narrowing of the left main coronary artery. Group 1 patients were treated with patch aortoplasty encompassing the left main ostium and Supravalvular Aortic Stenosis. Group 2 patients were treated with excision of the fused leaflet from the Aortic wall and patch aortoplasty. Group 3 patients were treated with bypass grafting and aortoplasty. Results: Surgical strategy was determined by coronary angiography and intraoperative assessment of coronary anatomy. There was 1 early death. All surviving patients underwent echocardiography with or without postoperative catheterization. The mean postoperative Supravalvular gradient for 7 patients was 8 mm Hg (range 2-15 mm Hg). One patient required reoperation for a residual Aortic gradient as a result of Aortic arch involvement. No evidence of left main coronary artery Stenosis was seen in groups 1 and 2; bypass grafts were patent in group 3 patients at a mean follow-up of 54.8 months. Conclusion: Three subtypes of left main coronary Stenosis with Supravalvular Aortic Stenosis are described. Each anatomic type mandates an individual surgical approach. Favorable surgical outcomes are achievable with each category. (J Thorac Cardiovasc Surg 2000;120:1040-6)
Chan Uhng Joo - One of the best experts on this subject based on the ideXlab platform.
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demonstration of peripheral pulmonary Stenosis and Supravalvular Aortic Stenosis by different cardiac imaging modalities in a patient with williams syndrome usefulness of noninvasive imaging studies
International Journal of Cardiology, 2008Co-Authors: Jaehyeong Park, Hyunsook Kim, Gong Yong Jin, Chan Uhng JooAbstract:With technical improvement, noninvasive cardiac imaging modalities, including multislice computed tomography and magnetic resonance imaging, can offer sufficient imaging quality to differentiate cardiac anatomies. These noninvasive modalities also can identify Aortic and pulmonary vascular abnormalities clearly in the same study. We report a case with severe pulmonary hypertension associated with peripheral pulmonary Stenosis and Supravalvular Aortic Stenosis in a 29-year-old woman with Williams syndrome, which was identified similarly with both invasive and noninvasive imaging modalities. The need for invasive tests can be reduced with appropriate improvement and validation of these noninvasive tests.
Hongyu Zhao - One of the best experts on this subject based on the ideXlab platform.
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modeling Supravalvular Aortic Stenosis syndrome with human induced pluripotent stem cells
Circulation, 2012Co-Authors: Yongming Ren, Oscar Bartulos, Min Young Lee, Zhichao Yue, Kunyong Kim, Peter J Amos, Esra Cagavi Bozkulak, Amulya Iyer, Wei Zheng, Hongyu ZhaoAbstract:Background—Supravalvular Aortic Stenosis (SVAS) is caused by mutations in the elastin (ELN) gene and is characterized by abnormal proliferation of vascular smooth muscle cells (SMCs) that can lead to narrowing or blockage of the ascending aorta and other arterial vessels. Having patient-specific SMCs available may facilitate the study of disease mechanisms and development of novel therapeutic interventions. Methods and Results—Here, we report the development of a human induced pluripotent stem cell (iPSC) line from a patient with SVAS caused by the premature termination in exon 10 of the ELN gene resulting from an exon 9 four-nucleotide insertion. We showed that SVAS iPSC-derived SMCs (iPSC-SMCs) had significantly fewer organized networks of smooth muscle α-actin filament bundles, a hallmark of mature contractile SMCs, compared with control iPSC-SMCs. The addition of elastin recombinant protein or enhancement of small GTPase RhoA signaling was able to rescue the formation of smooth muscle α-actin filament...