{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T04:03:16Z","timestamp":1778817796899,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,4,23]],"date-time":"2013-04-23T00:00:00Z","timestamp":1366675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Thoracic aortic aneurysm and dissection (TAAD) are associated with connective tissue disorders like Marfan syndrome and Loeys\u2013Dietz syndrome, caused by mutations in the fibrillin\u20101, the TGF\u03b2\u2010receptor 1\u2010 and \u20102 genes, the <jats:italic>SMAD3<\/jats:italic> and <jats:italic>TGF\u03b22<\/jats:italic> genes, but have also been ascribed to <jats:italic>ACTA2<\/jats:italic> gene mutations in adults, spread throughout the gene. We report on a novel de novo c.535C\u2009&gt;\u2009T in exon 6 leading to p.R179C aminoacid substitution in <jats:italic>ACTA2<\/jats:italic> in a toddler girl with primary pulmonary hypertension, persistent ductus arteriosus, extensive cerebral white matter lesions, fixed dilated pupils, intestinal malrotation, and hypotonic bladder. Recently, de novo <jats:italic>ACTA2<\/jats:italic> R179H substitutions have been associated with a similar phenotype and additional cerebral developmental defects including underdeveloped corpus callosum and vermis hypoplasia in a single patient. The patient here shows previously undescribed abnormal lobulation of the frontal lobes and position of the gyrus cinguli and rostral dysplasis of the corpus callosum; she died at the age of 3 years during surgery due to vascular fragility and rupture of the ductus arteriosus. Altogether these observations support a role of <jats:italic>ACTA2<\/jats:italic> in brain development, especially related to the arginine at position 179. Although all previously reported patients with R179H substitution successfully underwent the same surgery at younger ages, the severe outcome of our patient warns against the devastating effects of the R179C substitution on vasculature. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.35858","type":"journal-article","created":{"date-parts":[[2013,4,23]],"date-time":"2013-04-23T20:15:52Z","timestamp":1366748152000},"page":"1376-1380","source":"Crossref","is-referenced-by-count":34,"title":["<i>ACTA2<\/i> mutation with childhood cardiovascular, autonomic and brain anomalies and severe outcome"],"prefix":"10.1002","volume":"161","author":[{"given":"Marije E.C.","family":"Meuwissen","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Erasmus University Medical Center Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maarten H.","family":"Lequin","sequence":"additional","affiliation":[{"name":"Department of Radiology Erasmus University Medical Center Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Bindels\u2010de Heus","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Erasmus University Medical Center Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hennie T.","family":"Bruggenwirth","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus University Medical Center Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maarten F.C.M.","family":"Knapen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Prenatal Medicine Erasmus University Medical Center Rotterdam The 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