{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:36:57Z","timestamp":1790743017033,"version":"4.1.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>\n              Elastin insufficiency causes recurrent vascular stenoses. Hemizygous deletion of the elastin gene (\n              <jats:italic>ELN<\/jats:italic>\n              ) causes Williams-Beuren syndrome (WBS), while single nucleotide variants in\n              <jats:italic>ELN<\/jats:italic>\n              cause nonsyndromic supravalvar aortic stenosis (SVAS). Our objective was to compare cardiovascular disease outcomes in patients with WBS and nonsyndromic SVAS.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Patients (81 WBS, 42 nonsyndromic SVAS) with cardiovascular disease were included in this retrospective single center study. Freedom from surgical and catheter interventions and reinterventions was compared. Vascular tissue from 8 patients and 6 controls was analyzed for arterial wall architecture.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Patients with nonsyndromic SVAS presented at a younger age (median 0.3 [0.4\u20130.7] years) compared with patients with WBS (1.3 [0.2\u20133.0] years) and had lower freedom from surgical\/catheter interventions compared with patients with WBS, with median event-free survival 1.1 (0.3\u20135.9) versus 4.7 (2.4\u201313.3) years, respectively (hazard ratio, 1.62 [95% CI, 1.02\u20132.56];\n              <jats:italic>P<\/jats:italic>\n              =0.04). Patients with nonsyndromic SVAS also had a lower freedom from reinterventions (\n              <jats:italic>P<\/jats:italic>\n              =0.054 by log-rank test). This was related in part to a higher frequency of primary and reinterventions for concomitant valvar aortic stenosis. Histology revealed abnormal intimal and medial thickening, disorganized and fragmented elastic fibers, reduced smooth muscle calponin expression, and increased macrophage marker, CD68, expression in the arterial walls in patients with WBS and nonsyndromic SVAS compared with controls.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Patients with nonsyndromic SVAS require early and more frequent vascular and valvular interventions and reinterventions, in particular for concomitant valvar aortic stenosis compared with patients with WBS. This provides important prognostic information to guide counseling of affected families with cardiovascular disease and may guide primary intervention strategies based on predicted risk of restenosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.120.002971","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T21:09:12Z","timestamp":1600808952000},"source":"Crossref","is-referenced-by-count":25,"title":["Genetic Diagnosis and the Severity of Cardiovascular Phenotype in Patients With Elastin Arteriopathy"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0544-3102","authenticated-orcid":true,"given":"Sandar","family":"Min","sequence":"first","affiliation":[{"name":"Genetics &amp; Genome Biology Program (S. Min, C.K., J.B., R.Y., S. Mital), Hospital for Sick Children, Toronto."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8085-8493","authenticated-orcid":true,"given":"Caroline","family":"Kinnear","sequence":"additional","affiliation":[{"name":"Genetics &amp; Genome Biology Program (S. Min, C.K., J.B., R.Y., S. Mital), Hospital for Sick Children, Toronto."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa C.A.","family":"D\u2019Alessandro","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Women and Children\u2019s Health, Trillium Health Partners, Mississauga (L.C.A.D.)."},{"name":"Department of Pediatrics (L.C.A.D.), University of Toronto."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0930-1857","authenticated-orcid":true,"given":"Jade","family":"Bouwmeester","sequence":"additional","affiliation":[{"name":"Genetics &amp; Genome Biology Program (S. Min, C.K., J.B., R.Y., S. Mital), Hospital for Sick Children, Toronto."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick","family":"Yao","sequence":"additional","affiliation":[{"name":"Genetics &amp; Genome Biology Program (S. Min, C.K., J.B., R.Y., S. Mital), Hospital for Sick Children, Toronto."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Chiasson","sequence":"additional","affiliation":[{"name":"Department of Paediatric Laboratory Medicine, Laboratory Medicine and Pathobiology (D.C.), Hospital for Sick Children, Toronto."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3319-2793","authenticated-orcid":true,"given":"Fred","family":"Keeley","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine (F.K.), Hospital for Sick Children, Toronto."},{"name":"Department of Paediatric Laboratory Medicine, Laboratory Medicine and Pathobiology (D.C.), Hospital for Sick Children, Toronto."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7643-4484","authenticated-orcid":true,"given":"Seema","family":"Mital","sequence":"additional","affiliation":[{"name":"Genetics &amp; Genome Biology Program (S. Min, C.K., J.B., R.Y., S. Mital), Hospital for Sick Children, Toronto."},{"name":"Department of Pediatrics (S. 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