{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:26Z","timestamp":1753869686575,"version":"3.41.2"},"reference-count":38,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T00:00:00Z","timestamp":1593388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"RCB Bank"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Thoracic aortic aneurysm and dissection (TAA\/D) represents a potentially lethal disease group characterized by an increased risk of dissection or rupture. Only a small percentage (approximately 30%) of individuals with nonsyndromic familial TAA\/D have a pathogenic variant in one of the genes that have been found to be associated with the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A targeted sequencing panel and direct sequencing approach were used to identify causative mutations in the index patients and other family members.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this study we report two apparently unrelated Cypriot families with nonsyndromic familial TAA\/D. The proband A is a female patient diagnosed with TAA\/D and intracranial aneurysm and opted for an elective intervention. The proband B is a male patient who was diagnosed with TAA\/D and underwent cardiac surgery. Sequencing analysis identified a novel splice site variant (c.871+1G&gt;A) in <jats:italic>SMAD3<\/jats:italic> which is shown to be associated with the disease. Analysis of mRNA from the patient's tissue confirmed aberrant splicing and exon 6 skipping.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings expand the mutation spectrum of variants that have been shown to be associated with nonsyndromic familial TAA\/D. This study demonstrates the importance of a comprehensive clinical and genetic evaluation aiming at early diagnosis and intervention.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1378","type":"journal-article","created":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T10:52:21Z","timestamp":1593427941000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification of novel splice mutation in <i>SMAD3<\/i> in two Cypriot families with nonsyndromic thoracic aortic aneurysm. Two case reports"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5785-8601","authenticated-orcid":false,"given":"Anna","family":"Keravnou","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Genetics and The Laboratory of Forensic Genetics The Cyprus Institute of Neurology and Genetics Nicosia Cyprus"},{"name":"Cyprus School of Molecular Medicine The Cyprus Institute of Neurology and Genetics Nicosia Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evy","family":"Bashiardes","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Genetics and The Laboratory of Forensic Genetics The Cyprus Institute of Neurology and Genetics Nicosia Cyprus"},{"name":"Cyprus School of Molecular Medicine The Cyprus Institute of Neurology and Genetics Nicosia Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vassilis","family":"Barberis","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Cardiovascular Surgery American Medical Center Nicosia Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyriaki","family":"Michailidou","sequence":"additional","affiliation":[{"name":"Cyprus School of Molecular Medicine The Cyprus Institute of Neurology and Genetics Nicosia Cyprus"},{"name":"Biostatistics Unit The Cyprus Institute of Neurology &amp; Genetics Nicosia Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marinos","family":"Soteriou","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Cardiovascular Surgery American Medical Center Nicosia Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George A.","family":"Tanteles","sequence":"additional","affiliation":[{"name":"Clinical Genetics Clinic The Cyprus Institute of Neurology &amp; Genetics Nicosia Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marios A.","family":"Cariolou","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Genetics and The Laboratory of Forensic Genetics The Cyprus Institute of Neurology and Genetics Nicosia Cyprus"},{"name":"Cyprus School of Molecular Medicine The Cyprus Institute of Neurology and Genetics Nicosia Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,6,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096387"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1110s43"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.029538"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.140645"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100038\u20101639612"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.12945\/j.aorta.2017.17.003"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010014\u20100221\u20106"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2004.07.016"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1132"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp215"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.7453\/gahmj.2013.008"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881\u2010016\u20100326\u2010y"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/24.17.3439"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399\u20100004.2012.01931.x"},{"volume-title":"SMAD3 pathogenic variants: Risk for thoracic aortic disease and associated complications from the Montalcino Aortic Consortium","year":"2019","author":"Hostetler E. 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