Diagnostic Yield of Clinical Next-Generation Sequencing Panels for Epilepsy | Epilepsy and Seizures | JAMA Neurology

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Several studies have addressed the diagnostic yield and cost of NGS relative to other types of DNA testing. G-banded karyotyping identifies chromosomal aberrations and has a 3%..." /> <meta property="fb:pages" content="87087958340" /> <meta property="fb:pages" content="122228711814384" /> <meta property="fb:pages" content="1648414928738217" /> <meta property="fb:pages" content="117506346528" /> <meta property="fb:pages" content="97538728726" /> <meta property="fb:pages" content="114116793520" /> <meta property="fb:pages" content="100679858757" /> <meta property="fb:pages" content="759822190741773" /> <meta property="fb:pages" content="100265333750" /> <meta property="fb:pages" content="234770525256" /> <meta property="fb:pages" content="98784919862" /> <meta property="fb:pages" content="120829458202" /> <meta property="fb:pages" content="124842870398" /> <meta property="fb:pages" content="110245330325636" /> <meta name="twitter:card" content="summary_large_image" /> <meta name="twitter:site" content="@JAMANeuro" /> <meta name="twitter:image" content="https://cdn.jamanetwork.com/ama/content_public/journal/neur/930106/nld140001t1.png?Expires=2147483647&Signature=2yPfXFPYiRbU-ZOzOP7S7xL3yEtVDKEGRAlMovX~yzPgVTJ75QWAdQCcu2ltPwG5SACqBUZGlbBdiBH6QYr7QtCobJ4vIXNTW87B5Hw~QBwnC8kDqX8m2jwgmo0Dwv-1~Xudry1D7AuHM9zSzcN3NxuEyIw4vVh4gY2PdOY7YUuOq6HJrpO74eawq3wGeo4S0s0iPKvPwaV9QWmmDuAR~ydJwhdj3Ad8A128IPUeTUkXikUXxfAOx~R~cDEpjKmX8lSDPwCFPVfVODGVtGBahJwYJI~IHuTMPDQJom3wSARPF0iStfTgitlvnD5T5QHREMDZk8ho41H0D4prXQ0XfA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" /> <script type="application/ld+json"> { "@context": "https://schema.org/", "@type": "Article", "headline": "Diagnostic Yield of Clinical Next-Generation Sequencing Panels for Epilepsy", "author": "Jason Wang, MD", "url": "https://jamanetwork.com/journals/jamaneurology/fullarticle/1867434", "datePublished": "2014-05-01", "description": "During the past 2 years, next-generation DNA sequencing (NGS) has become a widespread diagnostic tool in neurology. Several studies have addressed the diagnostic yield and cost of NGS relative to other types of DNA testing. G-banded karyotyping identifies chromosomal aberrations and has a 3% diagnostic yield for unexplained developmental disabilities or other congenital anomalies. 1 In comparison, chromosomal microarrays detect gene copy number variations and have a yield of 15% to 20% for the same disorder categories. 1 Next-generation DNA sequencing, in the format of whole-exome sequencing (WES), can be diagnostic in 25% of neurogenetic cases. 2 Similarly, whole-genome sequencing (WGS) with NGS has a reported diagnostic yield of 27% in children and adults with a broad variety of diseases. 3 In contrast to WES and WGS, targeted NGS panels focus on subsets (dozens to hundreds) of genes associated with specific phenotypes. For example, targeted NGS directed at a single disease category, such as congenital glycosylation disorders, has a reported diagnostic yield of 14.8%. 4 Given the prevalence of pediatric epilepsy, we set out to critically assess the diagnostic yield of an NGS panel for epilepsy in a pediatric tertiary care hospital.", "publisher": { "@type": "Organization", "name": "JAMA Network", "logo": { "@type": "ImageObject", "url": "//cdn.jamanetwork.com/UI/app/img/favicons/neur/favicon.ico" } }, "image": [ "https://cdn.jamanetwork.com/ama/content_public/journal/neur/930106/nld140001t1.png?Expires=2147483647&Signature=2yPfXFPYiRbU-ZOzOP7S7xL3yEtVDKEGRAlMovX~yzPgVTJ75QWAdQCcu2ltPwG5SACqBUZGlbBdiBH6QYr7QtCobJ4vIXNTW87B5Hw~QBwnC8kDqX8m2jwgmo0Dwv-1~Xudry1D7AuHM9zSzcN3NxuEyIw4vVh4gY2PdOY7YUuOq6HJrpO74eawq3wGeo4S0s0iPKvPwaV9QWmmDuAR~ydJwhdj3Ad8A128IPUeTUkXikUXxfAOx~R~cDEpjKmX8lSDPwCFPVfVODGVtGBahJwYJI~IHuTMPDQJom3wSARPF0iStfTgitlvnD5T5QHREMDZk8ho41H0D4prXQ0XfA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" ], "articleSection": [ "Methods", "Results", "Discussion", "Article Information" ], "keyWords": "epilepsy, massively-parallel sequencing, high-throughput nucleotide sequencing" } </script> <meta name="citation_author" content="Jason Wang" /><meta name="citation_author_institution" content="Department of Pathology, Children’s Medical Center, University of Texas Southwestern Medical Center, Dallas" /><meta name="citation_author" content="Garrett Gotway" /><meta name="citation_author_institution" content="Division of Genetics and Metabolism, Department of Pediatrics, Children’s Medical Center, University of Texas Southwestern Medical Center, Dallas" /><meta name="citation_author" content="Juan M. Pascual" /><meta name="citation_author_institution" content="Rare Brain Disorders Program, Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas" /><meta name="citation_author" content="Jason Y. Park" /><meta name="citation_author_institution" content="Department of Pathology, Children’s Medical Center, University of Texas Southwestern Medical Center, Dallas" /><meta name="citation_title" content="Diagnostic Yield of Clinical Next-Generation Sequencing Panels for Epilepsy" /><meta name="citation_firstpage" content="650" /><meta name="citation_lastpage" content="651" /><meta name="citation_doi" content="10.1001/jamaneurol.2014.405" /><meta name="citation_keyword" content="epilepsy" /><meta name="citation_keyword" content="massively-parallel genome sequencing" /><meta name="citation_keyword" content="high-throughput nucleotide sequencing" /><meta name="citation_journal_title" content="JAMA Neurology" /><meta name="citation_journal_abbrev" content="JAMA Neurol" /><meta name="citation_volume" content="71" /><meta name="citation_issue" content="5" /><meta name="citation_publication_date" content="2014/05/01" /><meta name="citation_issn" content="2168-6149" /><meta name="citation_publisher" content="American Medical Association" /><meta name="citation_reference" content="citation_title=Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies.; citation_author=Miller DT; citation_author=Adam MP; citation_author=Aradhya S; citation_journal_title=Am J Hum Genet; citation_year=2010; citation_volume=86; citation_issue=5; citation_pages=749-764; " /><meta name="citation_reference" content="citation_title=Clinical whole-exome sequencing for the diagnosis of mendelian disorders.; citation_author=Yang Y; citation_author=Muzny DM; citation_author=Reid JG; citation_journal_title=N Engl J Med; citation_year=2013; citation_volume=369; citation_issue=16; citation_pages=1502-1511; " /><meta name="citation_reference" content="citation_title=Genomics in clinical practice: lessons from the front lines.; citation_author=Jacob HJ; citation_author=Abrams K; citation_author=Bick DP; citation_journal_title=Sci Transl Med; citation_year=2013; citation_volume=5; citation_issue=194; citation_pages=194cm5" /><meta name="citation_reference" content="citation_title=Molecular diagnostic testing for congenital disorders of glycosylation (CDG): detection rate for single gene testing and next generation sequencing panel testing.; citation_author=Jones MA; citation_author=Rhodenizer D; citation_author=da Silva C; citation_journal_title=Mol Genet Metab; citation_year=2013; citation_volume=110; citation_issue=1-2; citation_pages=78-85; " /><meta name="citation_reference" content="citation_title=Evidence report: genetic and metabolic testing on children with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.; citation_author=Michelson DJ; citation_author=Shevell MI; citation_author=Sherr EH; citation_author=Moeschler JB; citation_author=Gropman AL; citation_author=Ashwal S; citation_journal_title=Neurology; citation_year=2011; citation_volume=77; citation_issue=17; citation_pages=1629-1635; " /><meta name="citation_reference" content="Ambry Genetics. http://www.ambrygen.com. Accessed February 2, 2014. " /><meta name="citation_reference" content="OMIM gene map statistics.http://www.omim.org/statistics/geneMap. Accessed February 2, 2014. " /><meta name="citation_reference" content="The Human Gene Mutation database.http://www.hgmd.cf.ac.uk/ac/index.php. Accessed February 2, 2014. " /><meta name="citation_fulltext_world_readable" content="" /><meta name="citation_pdf_url" content="https://jamanetwork.com/journals/jamaneurology/articlepdf/1867434/nld140001.pdf" /> <meta name="citation_xml_url" content="https://datafeed.jamanetwork.com/journals/jamaneurology/xml/1867434" /> <title>Diagnostic Yield of Clinical Next-Generation Sequencing Panels for Epilepsy | Epilepsy and Seizures | JAMA Neurology | JAMA Network</title> <meta name="description" content="During the past 2 years, next-generation DNA sequencing (NGS) has become a widespread diagnostic tool in neurology. 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Comparison of NGS Panel, WES, and Sanger Sequencing</div><a class="figure-table-anchor" id="nld140001t1"> </a><div class="figure-table-links right"><a class="view-large figure-table-link is-b desktop-only" path-from-xml="nld140001t1" href="https://cdn.jamanetwork.com/ama/content_public/journal/neur/930106/nld140001t1.png?Expires=1735235077&Signature=3YKR4UK2ImZaRidxCihrMSkmom7SdjX9dZVQgXHwQg767zXCOQ5d6EzuXPdQidVH~QHr8p-HBJLP7WMgpPqFnGxUMuSuJeoKB6h~QDCP2oEvZLu3SRDm-hfBj2BspwXIMnOoG9-5bYP-qpCr4bOQm-2PpsHMrULKDG4jqgFpRkMiCLYP58QD6AfnoaROesDVay55tPyodwS03dOAiUGCc0QXakrKbBgrB3PTxIO39C4MLzSiPW1LZizBYol6DZI2M06KnGTeW4MysjvL-aykfwRaQ9INMILRkqtXZJJGeVoyjY7JJFanz4kbmrP3yYCkVqkYnSqMEum4ONMieMLBoA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" target="_blank" rel="nofollow"><span class="view-large-text">View Large</span></a><a class="download-ppt figure-table-link is-b stats-download-figure-table" path-from-xml="nld140001t1" href="/downloadimage.aspx?image=https://cdn.jamanetwork.com/ama/content_public/journal/neur/930106/nld140001t1.png?Expires=1735235077&Signature=3YKR4UK2ImZaRidxCihrMSkmom7SdjX9dZVQgXHwQg767zXCOQ5d6EzuXPdQidVH~QHr8p-HBJLP7WMgpPqFnGxUMuSuJeoKB6h~QDCP2oEvZLu3SRDm-hfBj2BspwXIMnOoG9-5bYP-qpCr4bOQm-2PpsHMrULKDG4jqgFpRkMiCLYP58QD6AfnoaROesDVay55tPyodwS03dOAiUGCc0QXakrKbBgrB3PTxIO39C4MLzSiPW1LZizBYol6DZI2M06KnGTeW4MysjvL-aykfwRaQ9INMILRkqtXZJJGeVoyjY7JJFanz4kbmrP3yYCkVqkYnSqMEum4ONMieMLBoA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA&sec=49919229&ar=1867434&imagename=&siteId=16" rel="nofollow"><span class="download-ppt-text">Download</span></a><a class="figure-table-twitter figure-table-link figure-table-social addthis_button_twitter is-b" rel="nofollow"><span class="share-text"> </span></a><a class="figure-table-facebook figure-table-link figure-table-social addthis_button_facebook is-b" rel="nofollow"><span class="share-text"> </span></a></div><div class="figure-table cf cb"><div class="figure-table-image"><a href="https://cdn.jamanetwork.com/ama/content_public/journal/neur/930106/nld140001t1.png?Expires=1735235077&Signature=3YKR4UK2ImZaRidxCihrMSkmom7SdjX9dZVQgXHwQg767zXCOQ5d6EzuXPdQidVH~QHr8p-HBJLP7WMgpPqFnGxUMuSuJeoKB6h~QDCP2oEvZLu3SRDm-hfBj2BspwXIMnOoG9-5bYP-qpCr4bOQm-2PpsHMrULKDG4jqgFpRkMiCLYP58QD6AfnoaROesDVay55tPyodwS03dOAiUGCc0QXakrKbBgrB3PTxIO39C4MLzSiPW1LZizBYol6DZI2M06KnGTeW4MysjvL-aykfwRaQ9INMILRkqtXZJJGeVoyjY7JJFanz4kbmrP3yYCkVqkYnSqMEum4ONMieMLBoA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" target="_blank" path-from-xml="nld140001t1" rel="nofollow"><img data-original="https://cdn.jamanetwork.com/ama/content_public/journal/neur/930106/m_nld140001t1.png?Expires=1735235077&Signature=zKYUjxyFoAVvzJ-SaG9ZsgNX~-g7~-N15I-9g9mrBRQDscDPDv0rJuUeQgUTlCzD1Tf21eK9vsNN4IJKU7LICDmGDdUcLs7j~fXAg-~gHev6JZFy-JYB-BExPfi0~3QiGja1r1d795lfffP7-nC68ADSR4iQHFr8TmV35lZ6g4HThZvuxxL0Tf4XICBH~GJGLmbKAlWnfsjr22bMLecdyKb1Jt5LqPrOeAm0vP1H0viIcegiQEqe4LubpZBuS4j~uthZ-v9Xh5mU5SYUePm76zUTIGHEj9xCaDn5CN~XCUo2vMs0iCm1SAWujSxJUBSNThG6Cb37f3DWKg7vxqvScA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" alt="Comparison of NGS Panel, WES, and Sanger Sequencing" class="content-img lazy" path-from-xml="nld140001t1" /></a></div></div><div class="table-caption"></div></div> </div> </div> <div id="multimedia-tab" class="resource-tab js-resource-tab multimedia-tab need-jobs-ad"> </div> <div id="supplemental-tab" class="resource-tab js-resource-tab supplemental-tab need-jobs-ad"> </div> <div id="references-tab" class="resource-tab js-resource-tab references-tab need-jobs-ad"> <div class="references-wrap"> <div class="widget-SectionDisplay widget-instance-AMA_References_Tab"> <div class="references"><div class="reference"><a class="reference-number" id="nld140001r1">1.</a><div class="reference-content">Miller DT, Adam MP, Aradhya S, et al. 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</span><span class="wi-fullname brand-fg"><a href="/searchresults?author=Garrett+Gotway&q=Garrett+Gotway" rel=nofollow target="_blank">Garrett Gotway, MD, PhD<sup>2</sup></a></span><span class='al-author-delim'>; </span><span class="wi-fullname brand-fg"><a href="/searchresults?author=Juan+M.+Pascual&q=Juan+M.+Pascual" rel=nofollow target="_blank">Juan M. Pascual, MD, PhD<sup>3</sup></a></span>; <a class="meta-authors--etal td-u stats-meta-authors--etal">et al</a></span> <span class="meta-authors--remaining"><span class="wi-fullname brand-fg"><a href="/searchresults?author=Jason+Y.+Park&q=Jason+Y.+Park" rel=nofollow target="_blank">Jason Y. Park, MD, PhD<sup>1</sup></a></span></span> </div> <div class="meta-author"> <a class="meta-author-title is-b stats-meta-author-toggle" data-tog-target=".meta-author-content">Author Affiliations</a> <a class="meta-articleinfo-jumplink section-jump-link scroll-to stats-scroll-to-articleinfo" data-tab-toggle=".tab-nav-full-text" href="#49919235">Article Information</a> <div class="meta-author-content"> <ul class="meta-author-affiliations"> <li class="meta-author-affiliation"> <div class="meta-author-name"><sup>1</sup>Department of Pathology, Children’s Medical Center, University of Texas Southwestern Medical Center, Dallas</div> </li> <li class="meta-author-affiliation"> <div class="meta-author-name"><sup>2</sup>Division of Genetics and Metabolism, Department of Pediatrics, Children’s Medical Center, University of Texas Southwestern Medical Center, Dallas</div> </li> <li class="meta-author-affiliation"> <div class="meta-author-name"><sup>3</sup>Rare Brain Disorders Program, Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas</div> </li> </ul> </div> </div> <div class="meta-citation-wrap"> <span class="meta-citation-journal-name">JAMA Neurol. </span><span class="meta-citation"> 2014;71(5):650-651. doi:10.1001/jamaneurol.2014.405</span> </div> </div> <div class="widget-EditorsChoice widget-instance-AMA_EditorsChoice_Links"> </div> <div class="widget-LinkedContentToolbar widget-instance-AMA_LinkedContentToolbar"> <div class="linked-content-toolbar"> <div class="hidden js-search-open-multimedia-by-default" showContentByDefault="False"></div> <div class="linked-content-controls"> <a class="linked-content-trigger td-n stats-graphical-abstract" href="#graphical-abstract-tab"> <i class="icon-visual-abstract"><span class="sr-t">visual abstract icon</span></i> <div class="trigger-text d-ib va-m ta-l fw-5">Visual <div>Abstract</div></div> </a> <a class="linked-content-trigger td-n stats-editorial-comment" href="#editorial-comment-tab"> <i class="icon-document"><span class="sr-t">editorial comment icon</span></i> <div class="trigger-text d-ib va-m ta-l fw-5">Editorial <div>Comment</div></div> </a> <a class="linked-content-trigger td-n stats-related-articles" href="#related-articles-tab"> <i class="icon-related"><span class="sr-t">related articles icon</span></i> <div class="trigger-text d-ib va-m ta-l fw-5">Related <div>Articles</div></div> </a> <a class="linked-content-trigger td-n stats-author-interviews" href="#author-interviews-tab"> <i class="icon-author_interview"><span class="sr-t">author interview icon</span></i> <div class="trigger-text d-ib va-m ta-l fw-5">Interviews</div> </a> <a class="linked-content-trigger td-n stats-more-multimedia" href="#more-multimedia-tab"> <i class="icon-multimedia"><span class="sr-t">multimedia icon</span></i> <div class="trigger-text d-ib va-m ta-l fw-5">Multimedia</div> </a> <a class="linked-content-trigger td-n stats-listen-to-this-article" href="#listen-to-this-article-tab"> <i class="icon-audio"><span class="sr-t">audio icon</span></i> <div class="trigger-text d-ib va-m ta-l fw-5">Listen to <div>this article</div></div> </a> </div> <div class="linked-content-tabs"> <div id="graphical-abstract-tab" class="linked-content-tab graphical-abstract-tab"> <div class="widget-SectionDisplay widget-instance-AMA_GraphicalAbstract_Tab"> </div> </div> <div id="editorial-comment-tab" class="linked-content-tab editorial-comment-tab"> <div class="widget-ArticleLinks widget-instance-AMA_LinkedContentToolbar_EditorialComments"> </div> </div> <div id="related-articles-tab" class="linked-content-tab related-article-tab"> <div class="widget-ArticleLinks widget-instance-AMA_LinkedContentToolbar_RelatedArticle"> </div> <div class="widget-ArticleLinks widget-instance-AMA_LinkedContentToolbar_RelatedEditorsChoices"> </div> </div> <div id="author-interviews-tab" class="linked-content-tab linked-author-interviews-tab"> <div class="widget-AudioPlayer widget-instance-AMA_LinkedContentToolbar_PlatformAudioPlayer_AuthorInterviews"> </div> </div> <div id="listen-to-this-article-tab" class="linked-content-tab linked-listen-to-this-article-tab"> <div class="widget-AudioPlayer widget-instance-AMA_LinkedContentToolbar_PlatformAudioPlayer_ListenToThisArticle"> </div> </div> <div id="more-multimedia-tab" class="linked-content-tab more-multimedia-tab"> </div> </div> </div> </div> <div class="widget-ArticleFulltext widget-instance-AMA_Article_FullText_Widget"> <div class="article-full-text" data-userHasAccess="True"> <a class="article-section-id-anchor" id="49919226"></a> <p class="para">During the past 2 years, next-generation DNA sequencing (NGS) has become a widespread diagnostic tool in neurology. Several studies have addressed the diagnostic yield and cost of NGS relative to other types of DNA testing. G-banded karyotyping identifies chromosomal aberrations and has a 3% diagnostic yield for unexplained developmental disabilities or other congenital anomalies.<sup><a href="#nld140001r1" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">1</a></sup> In comparison, chromosomal microarrays detect gene copy number variations and have a yield of 15% to 20% for the same disorder categories.<sup><a href="#nld140001r1" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">1</a></sup> Next-generation DNA sequencing, in the format of whole-exome sequencing (WES), can be diagnostic in 25% of neurogenetic cases.<sup><a href="#nld140001r2" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">2</a></sup> Similarly, whole-genome sequencing (WGS) with NGS has a reported diagnostic yield of 27% in children and adults with a broad variety of diseases.<sup><a href="#nld140001r3" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">3</a></sup> In contrast to WES and WGS, targeted NGS panels focus on subsets (dozens to hundreds) of genes associated with specific phenotypes. For example, targeted NGS directed at a single disease category, such as congenital glycosylation disorders, has a reported diagnostic yield of 14.8%.<sup><a href="#nld140001r4" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">4</a></sup> Given the prevalence of pediatric epilepsy, we set out to critically assess the diagnostic yield of an NGS panel for epilepsy in a pediatric tertiary care hospital.</p> <a class="article-section-id-anchor" id="49919227"></a> <div class="movable-ad-target bta"> </div> <div class="h3 cb section-type-section "> <div class="heading-text thm-col sb-sc"> Methods </div> </div> <a class="article-section-id-anchor" id="49919228"></a> <p class="para">The University of Texas Southwestern Medical Center institutional review board approved this retrospective study; patient informed consent was waived. We conducted a 1-year retrospective review of all patients with epilepsy treated at our institution who received targeted NGS on peripheral blood by either the 2012 GeneDx Comprehensive (53 genes) or Infantile (38 genes) Epilepsy Gene Panels. The patients’ clinical histories were reviewed to determine the relevance (ie, diagnostic yield) of the targeted NGS test results. In addition, we compared the cost of the targeted NGS panels, subsets of single-gene sequencing tests, and WES (<a href="#nld140001t1" class="table-link section-jump-link" data-tab-toggle=".tab-nav-figure-table">Table</a>).</p> <a class="article-section-id-anchor" id="49919230"></a> <div class="h3 cb section-type-section "> <div class="heading-text thm-col sb-sc"> Results </div> </div> <a class="article-section-id-anchor" id="49919231"></a> <p class="para">In 2012, 28 patients were tested using either the GeneDx Comprehensive or the Infantile Epilepsy Gene Panels. Six patients harbored pathogenic or likely pathogenic mutations in 5 epilepsy-associated genes (<i>TCF4</i>, <i>SCN1A</i>, <i>CDKL5</i>, <i>KCNQ2</i>, and <i>POLG</i>) and 11 patients were found to have novel missense variants that were classified as variants of unknown significance in 8 genes (<i>GABRG2</i>, <i>MECP2</i>, <i>PNPO</i>, <i>SCN1A</i>, <i>SCN2A</i>, <i>SCN1B</i>, <i>SLC9A6</i>, and <i>TSC2</i>). All of the pathogenic mutations had been previously characterized as such in the literature; novel variants that were likely pathogenic were reported as variants of unknown significance. The diagnostic yield of these disease-targeted NGS panels was 21.4% (6 of 28 patients), on par with WES or WGS.<sup><a href="#nld140001r2" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">2</a></sup><sup>-<a href="#nld140001r2" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">4</a></sup> If the GeneDx criteria for prior reporting in diagnosing pathogenicity had been used in a recent study of clinical WES, the WES diagnostic yield would have been only 18%<sup><a href="#nld140001r2" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">2</a></sup>; therefore, with equivalent reporting criteria, these NGS panel tests for epilepsy would have a superior diagnostic yield compared with WES.</p> <a class="article-section-id-anchor" id="49919232"></a> <p class="para">The Comprehensive and Infantile Epilepsy Gene Panels cost $5750 and $4780, respectively. Whole-exome sequencing costs up to $15 129.<sup><a href="#nld140001r6" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">6</a></sup> In contrast, examining a subset of 3 commonly tested epilepsy genes by Sanger sequencing (<i>SLC2A1</i>, <i>MECP2</i>, and <i>SCN1A</i>) costs $7300.<sup><a href="#nld140001r6" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">6</a></sup> We concluded that there is a cost advantage in the use of NGS technology compared with traditional Sanger sequencing.</p> <a class="article-section-id-anchor" id="49919233"></a> <div class="h3 cb section-type-section "> <div class="heading-text thm-col sb-sc"> Discussion </div> </div> <a class="article-section-id-anchor" id="49919234"></a> <p class="para">Whole-exome sequencing analyzes, with varying quality, more than 20 000 genes, but the Online Mendelian Inheritance in Man and the Human Gene Mutation Database currently include information for 3131 and 6137 genes, respectively.<sup><a href="#nld140001r7" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">7</a></sup><sup>,<a href="#nld140001r8" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">8</a></sup> Indeed, a recent study of WES reporting a diagnostic yield of 25% included 48 novel variants that had not been previously reported.<sup><a href="#nld140001r2" class="ref-link section-jump-link" data-tab-toggle=".tab-nav-references">2</a></sup> In this review of targeted NGS panels for epilepsy, the diagnostic yield was, in aggregate, similar to WES and achieved at a lower cost. In summary, targeted NGS gene panels are a cost-effective alternative to both Sanger sequencing of individual genes and WES for the genetic diagnosis of epilepsy.</p> <a class="article-section-id-anchor" id="49919235"></a> <div class="h3 cb section-type-acknowledgements has-back-to-top"> <a href="#top" class="section-jump-link back-to-top" data-tab-toggle=".tab-nav-full-text">Back to top</a> <div class="heading-text thm-col sb-sc"> Article Information </div> </div> <p class="authorInfoSection"><strong>Corresponding Author:</strong> Jason Wang, MD, Department of Pathology, Children’s Medical Center, 1935 Medical District Dr, Dallas, TX 75235 (<a href="mailto:jason.wang@utsouthwestern.edu" target="_blank">jason.wang@utsouthwestern.edu</a>).</p><p class="paraauthor-contributions"><strong>Author Contributions: </strong>Drs Wang and Park had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.</p><p class="para"><i>Study concept and design: </i>All authors.</p><p class="para"><i>Acquisition, analysis, or interpretation of data: </i>All authors.</p><p class="para"><i>Drafting of the manuscript: </i>All authors.</p><p class="para"><i>Critical revision of the manuscript for important intellectual content: </i>All authors.</p><p class="para"><i>Administrative, technical, or material support:</i> All authors.</p><p class="para"><i>Study supervision: </i>Pascual, Park.</p><p class="parafinancial-disclosure"><strong>Conflict of Interest Disclosures:</strong> Dr Park is a member of the Scientific Advisory Board of Fujirebio Inc. No other disclosures were reported.</p><p class="parafunding-statement"><strong>Funding/Support:</strong> Drs Pascual and Park are supported by National Institutes of Health Office of Rare Diseases Research: Collaboration, Education, and Test Translation (CETT) program for rare genetic diseases.</p><p class="para"><strong>Role of the Sponsor:</strong> The National Institutes of Health had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.</p> <a class="article-section-id-anchor" id="49919236"></a> <div class="h3 cb section-type-references "> <div class="heading-text thm-col sb-sc"> References </div> </div> <div class="references"><div class="reference"><a class="reference-number" id="nld140001r1">1.</a><div class="reference-content">Miller DT, Adam MP, Aradhya S, et al. 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