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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2022-01-11T00:00:00-05:00" class="date-display-single">January 11, 2022</span></p><div class='syndicate'><h1>Genetics of sudden unexplained death in children</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<li>Researchers identified genetic mutations associated with sudden unexplained death in children, or SUDC.</li>
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<li>The results could lead to a better understanding of the causes of these deaths and suggest new approaches to prevent them.</li>
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2022/202201111-children.jpg?itok=QKUkSdY4&timestamp=1641851801 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2022/202201111-children.jpg?itok=uC0P7cQg&timestamp=1641851801 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2022/202201111-children.jpg?itok=s8lNMly4&timestamp=1641851801 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2022/202201111-children.jpg?itok=P7ppK1sH&timestamp=1641851801 1x" media="screen and (min-width: 0)" />
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2022/202201111-children.jpg?itok=QKUkSdY4&timestamp=1641851801" alt="Teddy bear sitting alone on couch" title="Teddy bear sitting alone on couch" />
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</picture><span class="caption">Researchers have been working to understand the causes of sudden unexplained death in children.</span><span class="credit">Ann in the uk / Shutterstock</span></div>
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</div><p>Approximately 1,800 children in the United States die from sudden, unexplained causes each year, most while asleep. When it happens in children under 1 year of age, it's called sudden infant death syndrome (SIDS). In children 1 year of age or older, it’s called sudden unexplained death in children (SUDC). While SIDS cases outnumber SUDC cases by four to one, research funding and published studies for SIDS have dwarfed that for SUDC.</p>
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<p>A research team led by Drs. Richard Tsien and Orrin Devinsky at the NYU Grossman School of Medicine sought to identify genetic mutations that might contribute to SUDC. To do so, they sequenced DNA from 124 SUDC cases and their parents. DNA was extracted from samples collected through the SUDC Registry and Research Collaborative.</p>
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<p>NIH’s National Institute on Drug Abuse (NIDA) and National Institute of Mental Health (NIMH) supported the work. Results appeared in <em>Proceedings of the National Academy of Sciences </em>on December 28, 2021.</p>
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<p>The team first sequenced whole exomes, the 1% of the human genome that codes for proteins. There weren’t enough subjects to uncover genetic associations in a broad, initial analysis. The researchers then focused on 137 genes associated with heart or seizure disorders, both of which can trigger sudden death.</p>
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<p>They found that in SUDC cases, these genes contained significantly more mutations than would be expected by chance. Most were “de novo” mutations, meaning that while they were found in the child, they weren’t found in either parent. A handful of potentially harmful mutations in these genes occurred in parents. In such cases, the mutation also showed up in the offspring 80% of the time—again, more often than would be expected by chance.</p>
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<p>The researchers identified 11 particular mutations that were likely to cause health problems. These mutations were estimated to contributed to death in 9% of cases. Many of the mutations occurred in a cluster of genes that regulate calcium in neurons and heart muscle cells. Calcium changes in these cells control nerve signal transmission and muscle contraction. Mutations in one of the genes, <em>RYR2</em>, have been linked to heart problems. Mutations in another, <em>CACNA1C</em>, have been linked to a rare disorder, called Timothy syndrome, that can affect the heart, limbs, muscle, and brain.</p>
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<p>The results suggest that altered calcium signaling may play a significant role in SUDC. They also highlight the importance of de novo mutations for SUDC risk. Studies in larger samples might reveal additional genetic risk factors. Identifying these risk factors is the first step towards developing life-saving medical interventions.</p>
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<p>“Our study is the largest of its kind to date, the first to prove that there are definite genetic causes of SUDC, and the first to fill in any portion of the risk picture,” Tsien says. “Along with providing comfort to parents, new findings about genetic changes involved will accumulate with time, reveal the mechanisms responsible, and serve as the basis for new treatment approaches.”</p>
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<p>—by Brian Doctrow, Ph.D.</p></div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/insights-into-genetic-causes-childhood-epilepsies" target="_top">Insights into Genetic Causes of Childhood Epilepsies</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/common-genetic-factors-found-5-mental-disorders" target="_top">Common Genetic Factors Found in 5 Mental Disorders</a></li><li><a href="https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Febrile-Seizures-Fact-Sheet" target="_top">Febrile Seizures Fact Sheet</a></li><li><a href="https://www.nichd.nih.gov/health/topics/sids" target="_top">Sudden Infant Death Syndrome (SIDS)</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="https://pubmed.ncbi.nlm.nih.gov/34930847/">De novo mutations in childhood cases of sudden unexplained death that disrupt intracellular Ca<sup>2+</sup> regulation.</a> Halvorsen M, Gould L, Wang X, Grant G, Moya R, Rabin R, Ackerman MJ, Tester DJ, Lin PT, Pappas JG, Maurano MT, Goldstein DB, Tsien RW, Devinsky O. <em>Proc Natl Acad Sci U S A</em>. 2021 Dec 28;118(52):e2115140118. doi: 10.1073/pnas.2115140118. PMID: 34930847.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Institute on Drug Abuse (NIDA) and National Institute of Mental Health (NIMH); SUDC Foundation; Finding a Cure for Epilepsy and Seizures (FACES); Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program.</p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-can-we-slow-aging">Research in Context: Can we slow aging?</a></p>
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|
||
<p><a href="https://www.nih.gov/news-events/nih-research-matters/brain-changes-observed-during-pregnancy">Brain changes observed during pregnancy</a></p>
|
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|
||
<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-detecting-cancer">Research in Context: Detecting cancer</a></p>
|
||
|
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/risk-future-burden-dementia-united-states">Risk and future burden of dementia in the United States </a></p>
|
||
|
||
<p><a href="https://www.nih.gov/news-events/nih-research-matters/complete-wiring-map-adult-fruit-fly-brain">Complete wiring map of an adult fruit fly brain</a></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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