{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:07:40Z","timestamp":1780916860005,"version":"3.54.1"},"reference-count":22,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T00:00:00Z","timestamp":1580860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T00:00:00Z","timestamp":1580860800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010805","name":"Forskningsr\u00e5det i Syd\u00f6stra Sverige","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010805","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Pathogenic variants in the\n                      <jats:italic>SMAD3<\/jats:italic>\n                      gene affecting the TGF\u2010\u03b2\/SMAD3 signaling pathway with aortic vessel involvement cause Loeys\u2010Dietz syndrome 3, also known as aneurysms\u2013osteoarthritis syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Description of clinical history of a family in Sweden using clinical data, DNA sequencing, bioinformatics, and pedigree analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We report a novel\n                      <jats:italic>SMAD3<\/jats:italic>\n                      variant, initially classified as a genetic variant of uncertain clinical significance (VUS), and later found to be co\u2010segregating with aortic dissection in the family. The index patient presented with a dissecting aneurysm of the aorta including the ascending, descending, and abdominal parts. Genotype analysis revealed a heterozygous missense\n                      <jats:italic>SMAD3<\/jats:italic>\n                      variant: NM_005902.3(\n                      <jats:italic>SMAD3<\/jats:italic>\n                      ): c.11576G\u00a0&gt;\u00a0C (p.Arg386Thr). The same variant was also identified in a 30\u00a0years old formalin\u2010fixed paraffin\u2010embedded block of tissue from a second cousin, who died at 26\u00a0years of age from a dissecting aneurysm of the aorta.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A \u201cvariant of uncertain significance\u201d according to the ACMG guidelines has always a scope for reappraisal. Genetic counselling to relatives, and the offering of surveillance service is important to families with aortic aneurysm disease. The report also highlight the potential use of FFPE analysis from deceased relatives to help in the interpretation of variants.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.1089","type":"journal-article","created":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T07:54:38Z","timestamp":1580889278000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Novel\n                    <i>SMAD3<\/i>\n                    p.Arg386Thr genetic variant co\u2010segregating with thoracic aortic aneurysm and dissection"],"prefix":"10.1002","volume":"8","author":[{"given":"Karolina","family":"Engstr\u00f6m","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics and Department of Clinical and Experimental Medicine Link\u00f6ping University Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farkas","family":"V\u00e1nky","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Vascular Surgery and Department of Medical and Health Sciences Link\u00f6ping University Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malin","family":"Rehnberg","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Department of Clinical and Experimental Medicine Link\u00f6ping University Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Trinks","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Department of Clinical and Experimental Medicine Link\u00f6ping University Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Jonasson","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Department of Clinical and Experimental Medicine Link\u00f6ping University Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Faculty of Medicine and Health \u00d6rebro University \u00d6rebro Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9474-6820","authenticated-orcid":false,"given":"Cecilia","family":"Gunnarsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Department of Clinical and Experimental Medicine Link\u00f6ping University Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.23.4.338"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.01.040"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-5214(97)70261-1"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejvs.2015.08.003"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2015.11.007"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.134.4.361"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2012.11.013"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.009762"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.04.003"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.11.3443"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055695"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.12945\/j.aorta.2015.14.062"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.11"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.248161"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A1651"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23407"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.744"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.12.052"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.12.029"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22977"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35852"}],"container-title":["Molecular Genetics &amp; 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