{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:50:24Z","timestamp":1790693424252,"version":"4.1.0"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec>\n            <jats:title>Objective:<\/jats:title>\n            <jats:p>\n              While rare variants in the\n              <jats:italic>COL5A1<\/jats:italic>\n              gene have been associated with classical Ehlers-Danlos syndrome and rarely with arterial dissections, recurrent variants in\n              <jats:italic>COL5A1<\/jats:italic>\n              underlying a systemic arteriopathy have not been described. Monogenic forms of multifocal fibromuscular dysplasia (mFMD) have not been previously defined.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results:<\/jats:title>\n            <jats:p>\n              We studied 4 independent probands with the\n              <jats:italic>COL5A1<\/jats:italic>\n              pathogenic variant c.1540G&gt;A, p.(Gly514Ser) who presented with arterial aneurysms, dissections, tortuosity, and mFMD affecting multiple arteries. Arterial medial fibroplasia and smooth muscle cell disorganization were confirmed histologically. The\n              <jats:italic>COL5A1<\/jats:italic>\n              c.1540G&gt;A variant is predicted to be pathogenic in silico and absent in gnomAD. The c.1540G&gt;A variant is on a shared 160.1 kb haplotype with 0.4% frequency in Europeans. Furthermore, exome sequencing data from a cohort of 264 individuals with mFMD were examined for\n              <jats:italic>COL5A1<\/jats:italic>\n              variants. In this mFMD cohort,\n              <jats:italic>COL5A1<\/jats:italic>\n              c.1540G&gt;A and 6 additional relatively rare\n              <jats:italic>COL5A1<\/jats:italic>\n              variants predicted to be deleterious in silico were identified and were associated with arterial dissections (\n              <jats:italic>P<\/jats:italic>\n              =0.005).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              <jats:italic>COL5A1<\/jats:italic>\n              c.1540G&gt;A is the first recurring variant recognized to be associated with arterial dissections and mFMD. This variant presents with a phenotype reminiscent of vascular Ehlers-Danlos syndrome. A shared haplotype among probands supports the existence of a common founder. Relatively rare\n              <jats:italic>COL5A1<\/jats:italic>\n              genetic variants predicted to be deleterious by in silico analysis were identified in \u22482.7% of mFMD cases, and as they were enriched in patients with arterial dissections, may act as disease modifiers. Molecular testing for\n              <jats:italic>COL5A1<\/jats:italic>\n              should be considered in patients with a phenotype overlapping with vascular Ehlers-Danlos syndrome and mFMD.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.119.313885","type":"journal-article","created":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T09:01:29Z","timestamp":1600333289000},"page":"2686-2699","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":52,"title":["A Novel Recurrent\n            <i>COL5A1<\/i>\n            Genetic Variant Is Associated With a Dysplasia-Associated Arterial Disease Exhibiting Dissections and Fibromuscular Dysplasia"],"prefix":"10.1161","volume":"40","author":[{"given":"Julie","family":"Richer","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Children\u2019s Hospital of Eastern Ontario, Ottawa, Canada (J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah L.","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Children\u2019s Hospital of Eastern Ontario, Ottawa, Canada (J.R.)."},{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine (H.L.H., Y.W., M.-L.Y., K.L.H., J.L., A.E.K., S.K.G.), University of Michigan Medical School, Ann Arbor."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6608-4310","authenticated-orcid":true,"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine (H.L.H., Y.W., M.-L.Y., K.L.H., J.L., A.E.K., S.K.G.), University of Michigan Medical School, Ann Arbor."},{"name":"Department of Human Genetics (H.L.H., Y.W., M.-L.Y., K.L.H., J.L., A.E.K., J.Z.L., S.K.G.), University of Michigan Medical School, Ann Arbor."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Lee","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine (H.L.H., Y.W., M.-L.Y., K.L.H., J.L., A.E.K., S.K.G.), University of Michigan Medical School, Ann Arbor."},{"name":"Department of Human Genetics (H.L.H., Y.W., M.-L.Y., K.L.H., J.L., A.E.K., J.Z.L., S.K.G.), University of Michigan Medical School, Ann Arbor."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina L.","family":"Hunker","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine (H.L.H., Y.W., M.-L.Y., K.L.H., J.L., A.E.K., S.K.G.), University of Michigan Medical School, Ann Arbor."},{"name":"Department of Human Genetics (H.L.H., Y.W., M.-L.Y., K.L.H., J.L., A.E.K., J.Z.L., S.K.G.), University of Michigan Medical School, Ann 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Department of Internal Medicine (H.L.H., Y.W., M.-L.Y., K.L.H., J.L., A.E.K., S.K.G.), University of Michigan Medical School, Ann Arbor."},{"name":"Department of Human Genetics (H.L.H., Y.W., M.-L.Y., K.L.H., J.L., A.E.K., J.Z.L., S.K.G.), University of Michigan Medical School, Ann Arbor."},{"name":"Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD (A.E.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather L.","family":"Gornik","sequence":"additional","affiliation":[{"name":"Heart and Vascular Institute (N.F.-M., S.L.H., H.L.G.), Cleveland Clinic, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad M.","family":"Brummett","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Michigan Medicine, University of Michigan, Ann Arbor (M.R.M., 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