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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2013-05-20T00:00:00-04:00" class="date-display-single">May 20, 2013</span></p><div class='syndicate'><h1>Clues to Congenital Heart Disease</h1><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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</div><p>A large-scale genomic analysis found that non-inherited mutations in hundreds of genes together account for about 1 in 10 cases of severe congenital heart defects. The findings bring us closer to understanding the most common type of birth defect.</p>
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<p>Congenital heart defects are problems with the heart’s structure that are present at birth. They range from simple defects with no symptoms to complex flaws with severe, life-threatening symptoms. These defects affect 8 out of every 1,000 newborns. More than a million adults nationwide are living with congenital heart disease.</p>
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<p>An international, multicenter collaborative research team performed genomic analyses to gain insights into the causes of congenital heart defects. The effort was supported largely by NIH’s National Heart, Lung and Blood Institute (NHLBI). The team used state-of-the-art sequencing and genome-mapping techniques to focus on the exome — the complete set of protein-coding regions in the genome. While the exome represents only about 1.5% of the genome, past studies have found that it harbors most disease-causing mutations.</p>
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<p>The researchers analyzed 362 parent-offspring trios, each of which included a child with congenital heart disease and his or her healthy parents. A group of 264 healthy parent-offspring trios served as controls for comparison. The results appeared online in <em>Nature</em> on May 12, 2013.</p>
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<p>The scientists found that about 10% of the participant cases were associated with spontaneous (or <em>de novo</em>) mutations, which arise during fetal development. Based on their results, the investigators were able to estimate that there may be several hundred genes in which <em>de novo</em> mutations could contribute to congenital heart disease.</p>
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<p>Many of the genes with spontaneous mutations are involved in the biological pathway for a type of epigenetic modification called histone 3 lysine 4 (H3K4) methylation. Epigenetic modifications are changes to DNA that affect gene expression without altering the genetic sequence itself. Targeted sequencing of these genes in larger groups of patients may reveal more about the role of these mutations.</p>
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<p>“These findings provide new insight into the causes of this common congenital disease,” says Dr. Richard Lifton of the Yale School of Medicine, a senior author of the paper. “Most interestingly, the set of genes mutated in congenital heart disease unexpectedly overlapped with genes and pathways mutated in autism. These findings suggest there may be common pathways that underlie a wide range of common congenital diseases.”</p>
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<p>While this study identified many genes involved in congenital heart disease, the findings still don’t resolve the causes of most cases. Other genes and molecular pathways that cause congenital heart disease remain to be discovered.</p>
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<p>— by Harrison Wein, Ph.D.</p>
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</div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="http://www.youtube.com/watch?v=33dmTyBGSGo" target="_top">Researchers Take Step in Unlocking the Causes of Congenital Heart Disease (video)</a></li><li><a href="http://www.nhlbi.nih.gov/health/health-topics/topics/chd/" target="_top">What Are Congenital Heart Defects?</a></li><li><a href="http://www.nhlbi.nih.gov/news/spotlight/success/congenital-heart-disease.html" target="_top">NHLBI Story of Success: Congenital Heart Disease</a></li><li><a href="http://www.benchtobassinet.net/" target="_top">NHLBI Bench to Bassinet Program</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="http://www.ncbi.nlm.nih.gov/pubmed/23665959">Nature</a>. 2013 May 12. doi: 10.1038/nature12141. [Epub ahead of print]. PMID: 23665959.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Heart, Lung, and Blood Institute (NHLBI) and National Human Genome Research Institute (NHGRI); and the Simons Foundation for Autism Research.</p>
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<h3 class="block__title">About NIH Research Matters</h3>
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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<p>ISSN 2375-9593</p>
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