{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:55:18Z","timestamp":1762102518350,"version":"3.41.2"},"reference-count":26,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,7,7]],"date-time":"2020-07-07T00:00:00Z","timestamp":1594080000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"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>Isomerism or heterotaxy syndrome is the loss of normal asymmetry of the internal thoraco\u2010abdominal organs in the left\u2010right axis and is associated with cardiovascular malformations. Mutations within <jats:italic>DNAH11<\/jats:italic> can be associated with primary ciliary dyskinesia and heterotaxy syndromes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report a family of healthy, nonconsanguinous parents with subsequent pregnancies demonstrating a novel likely pathogenic variant in <jats:italic>DNAH11<\/jats:italic> segregating in a sibship with varied presentations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>The first affected pregnancy presented with right atrial isomerism. Further DNA testing identified three variants in <jats:italic>DNAH11<\/jats:italic> related to primary ciliary dyskinesia: a maternally inherited heterozygous variant of unknown significance (VUS) c.2772G&gt;A (p.Met924Ile), a maternally inherited novel likely pathogenic variant c.11662C&gt;T (p.Arg3888Cys) as well as a paternally inherited pathogenic c.1648delA variant (p.Arg550GlyfsX16). The second pregnancy inherited the same variants including the pathogenic and likely pathogenic <jats:italic>DNAH11<\/jats:italic> variants and presented with left isomerism and extracardiac abnormalities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We present a novel likely pathogenic variant (c.11662C&gt;T) in <jats:italic>DNAH11<\/jats:italic> that has manifested in heterotaxy with variability in phenotypes for subsequent pregnancies of common parents. This report demonstrates that sibship illustrates potential variability in phenotypes associated with the same pathogenic variants within a family and highlights the difficulty in genetic counseling due to the variation in clinical presentation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1358","type":"journal-article","created":{"date-parts":[[2020,7,7]],"date-time":"2020-07-07T09:15:04Z","timestamp":1594113304000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A novel <i>DNAH11<\/i> variant segregating in a sibship with heterotaxy and implications for genetic counseling"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6719-4589","authenticated-orcid":false,"given":"Amirpouyan","family":"Namavarian","sequence":"first","affiliation":[{"name":"Faculty of Medicine University of Toronto Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anas","family":"Eid","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Toronto Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2477-1665","authenticated-orcid":false,"given":"Elaine Suk\u2010Ying","family":"Goh","sequence":"additional","affiliation":[{"name":"Laboratory Medicine and Genetics Trillium Health Partners Mississauga ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varsha","family":"Thakur","sequence":"additional","affiliation":[{"name":"Division of Cardiology Hospital for Sick Children Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,7,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/81695"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.152337699"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2015.01.038"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2016.07.002"},{"key":"e_1_2_8_6_1","first-page":"37","article-title":"Prenatal diagnosis of left isomerism with normal heart: A case report","volume":"3","author":"De Paola N.","year":"2009","journal-title":"Journal of Prenatal Medicine"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.14871"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S1047951107001138","article-title":"The nomenclature, definition and classification of cardiac structures in the setting of heterotaxy","volume":"17","author":"Jacobs J. 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