{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T13:33:31Z","timestamp":1783776811809,"version":"3.55.0"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,3,22]],"date-time":"2017-03-22T00:00:00Z","timestamp":1490140800000},"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":[[2017,4]]},"abstract":"<jats:sec><jats:label\/><jats:p>De novo heterozygous mutations changing R179 to histidine, leucine, or cysteine in the <jats:italic>ACTA2<\/jats:italic> gene are associated with Multisystemic Smooth Muscle Dysfunction Syndrome (MSMDS). Characteristic hallmarks of this condition, caused only by these specific <jats:italic>ACTA2<\/jats:italic> mutations, are congenital mydriasis (mid\u2010dilated, non\u2010reactive pupils), a large persistent ductus arteriosus (PDA), aortic aneurysms evolving during childhood, and cerebrovascular anomalies. We describe two patients, a 3\u2010day\u2010old newborn and a 26\u2010year\u2010old woman, with this unique mutation in association with a huge PDA and an aorto\u2010pulmonary window. In addition, one showed a coarctation of the aortic arch and the other a complete interruption of the aortic arch type A; thereby expanding the spectrum of cardiac congenital heart defect of this syndrome. Each patient displayed a huge PDA and an extra\u2010cardiovascular phenotype consistent with MSMDS. These observations exemplify that a functional alpha 2 smooth muscle actin is necessary for proper cardiovascular organ development, and demonstrate that a very exceptional congenital heart defect (aortopulmonary window) can be caused by a mutation in a gene encoding a contractile protein of vascular smooth muscle cells. \u00a9 2017 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38102","type":"journal-article","created":{"date-parts":[[2017,3,23]],"date-time":"2017-03-23T05:24:33Z","timestamp":1490246673000},"page":"959-965","source":"Crossref","is-referenced-by-count":10,"title":["Two patients with the heterozygous R189H mutation in <i>ACTA2<\/i> and Complex congenital heart defects expands the cardiac phenotype of multisystemic smooth muscle dysfunction syndrome"],"prefix":"10.1002","volume":"173","author":[{"given":"Thushiha","family":"Logeswaran","sequence":"first","affiliation":[{"name":"Department of Pediatric Cardiology Justus\u2010Liebig\u2010University 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