One NF1 Mutation may Conceal Another

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NF1 is caused by loss-of-function mutations in the NF1 gene, a negative regulator of the RAS-MAPK pathway. The NF1 gene has one of the highest mutation rates in human disorders, which may explain the outbreak of independent de novo variants in the same family. Here, we report the co-occurrence of pathogenic variants in the NF1 and SPRED1 genes in six families with NF1 and Legius syndrome, using next-generation sequencing. In five of these families, we observed the co-occurrence of two independent NF1 variants. All NF1 variants were classified as pathogenic, according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines. In the sixth family, one sibling inherited a complete deletion of the NF1 gene from her mother and carried a variant of unknown significance in the SPRED1 gene. This variant was also present in her brother, who was diagnosed with Legius syndrome, a differential diagnosis of NF1. This work illustrates the complexity of molecular diagnosis in a not-so-rare genetic disease." > <link rel="image_src" href="https://pub.mdpi-res.com/img/journals/genes-logo.png?8600e93ff98dbf14" > <meta name="dc.title" content="One NF1 Mutation may Conceal Another"> <meta name="dc.creator" content="Laurence Pacot"> <meta name="dc.creator" content="Cyril Burin des Roziers"> <meta name="dc.creator" content="Ingrid Laurendeau"> <meta name="dc.creator" content="Audrey Briand-Suleau"> <meta name="dc.creator" content="Audrey Coustier"> <meta name="dc.creator" content="Théodora Mayard"> <meta name="dc.creator" content="Camille Tlemsani"> <meta name="dc.creator" content="Laurence Faivre"> <meta name="dc.creator" content="Quentin Thomas"> <meta name="dc.creator" content="Diana Rodriguez"> <meta name="dc.creator" content="Sophie Blesson"> <meta name="dc.creator" content="Hélène Dollfus"> <meta name="dc.creator" content="Yvon-Gauthier Muller"> <meta name="dc.creator" content="Béatrice Parfait"> <meta name="dc.creator" content="Michel Vidaud"> <meta name="dc.creator" content="Brigitte Gilbert-Dussardier"> <meta name="dc.creator" content="Catherine Yardin"> <meta name="dc.creator" content="Benjamin Dauriat"> <meta name="dc.creator" content="Christian Derancourt"> <meta name="dc.creator" content="Dominique Vidaud"> <meta name="dc.creator" content="Eric Pasmant"> <meta name="dc.type" content="Article"> <meta name="dc.source" content="Genes 2019, Vol. 10, Page 633"> <meta name="dc.date" content="2019-08-22"> <meta name ="dc.identifier" content="10.3390/genes10090633"> <meta name="dc.publisher" content="Multidisciplinary Digital Publishing Institute"> <meta name="dc.rights" content="http://creativecommons.org/licenses/by/3.0/"> <meta name="dc.format" content="application/pdf" > <meta name="dc.language" content="en" > <meta name="dc.description" content="Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with complete penetrance but high variable expressivity. NF1 is caused by loss-of-function mutations in the NF1 gene, a negative regulator of the RAS-MAPK pathway. The NF1 gene has one of the highest mutation rates in human disorders, which may explain the outbreak of independent de novo variants in the same family. Here, we report the co-occurrence of pathogenic variants in the NF1 and SPRED1 genes in six families with NF1 and Legius syndrome, using next-generation sequencing. In five of these families, we observed the co-occurrence of two independent NF1 variants. All NF1 variants were classified as pathogenic, according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines. In the sixth family, one sibling inherited a complete deletion of the NF1 gene from her mother and carried a variant of unknown significance in the SPRED1 gene. This variant was also present in her brother, who was diagnosed with Legius syndrome, a differential diagnosis of NF1. This work illustrates the complexity of molecular diagnosis in a not-so-rare genetic disease." > <meta name="dc.subject" content="de novo variant" > <meta name="dc.subject" content="Legius syndrome" > <meta name="dc.subject" content="neurofibromatosis type 1" > <meta name="dc.subject" content="<i>NF1</i>" > <meta name="dc.subject" content="<i>SPRED1</i>" > <meta name ="prism.issn" content="2073-4425"> <meta name ="prism.publicationName" content="Genes"> <meta name ="prism.publicationDate" content="2019-08-22"> <meta name ="prism.volume" content="10"> <meta name ="prism.number" content="9"> <meta name ="prism.section" content="Article" > <meta name ="prism.startingPage" content="633" > <meta name="citation_issn" content="2073-4425"> <meta name="citation_journal_title" content="Genes"> <meta name="citation_publisher" content="Multidisciplinary Digital Publishing Institute"> <meta name="citation_title" content="One NF1 Mutation may Conceal Another"> <meta name="citation_publication_date" content="2019/9"> <meta name="citation_online_date" content="2019/08/22"> <meta name="citation_volume" content="10"> <meta name="citation_issue" content="9"> <meta name="citation_firstpage" content="633"> <meta name="citation_author" content="Pacot, Laurence"> <meta name="citation_author" content="Burin des Roziers, Cyril"> <meta name="citation_author" content="Laurendeau, Ingrid"> <meta name="citation_author" content="Briand-Suleau, Audrey"> <meta name="citation_author" content="Coustier, Audrey"> <meta name="citation_author" content="Mayard, Théodora"> <meta name="citation_author" content="Tlemsani, Camille"> <meta name="citation_author" content="Faivre, Laurence"> <meta name="citation_author" content="Thomas, Quentin"> <meta name="citation_author" content="Rodriguez, Diana"> <meta name="citation_author" content="Blesson, Sophie"> <meta name="citation_author" content="Dollfus, Hélène"> <meta name="citation_author" content="Muller, Yvon-Gauthier"> <meta name="citation_author" content="Parfait, Béatrice"> <meta name="citation_author" content="Vidaud, Michel"> <meta name="citation_author" content="Gilbert-Dussardier, Brigitte"> <meta name="citation_author" content="Yardin, Catherine"> <meta name="citation_author" content="Dauriat, Benjamin"> <meta name="citation_author" content="Derancourt, Christian"> <meta name="citation_author" content="Vidaud, Dominique"> <meta name="citation_author" content="Pasmant, Eric"> <meta name="citation_doi" content="10.3390/genes10090633"> <meta name="citation_id" content="mdpi-genes10090633"> <meta name="citation_abstract_html_url" content="https://www.mdpi.com/2073-4425/10/9/633"> <meta name="citation_pdf_url" content="https://www.mdpi.com/2073-4425/10/9/633/pdf?version=1566464889"> <link rel="alternate" type="application/pdf" title="PDF Full-Text" href="https://www.mdpi.com/2073-4425/10/9/633/pdf?version=1566464889"> <meta name="fulltext_pdf" content="https://www.mdpi.com/2073-4425/10/9/633/pdf?version=1566464889"> <meta name="citation_fulltext_html_url" content="https://www.mdpi.com/2073-4425/10/9/633/htm"> <link rel="alternate" type="text/html" title="HTML Full-Text" href="https://www.mdpi.com/2073-4425/10/9/633/htm"> <meta name="fulltext_html" content="https://www.mdpi.com/2073-4425/10/9/633/htm"> <link rel="alternate" type="text/xml" title="XML Full-Text" href="https://www.mdpi.com/2073-4425/10/9/633/xml"> <meta name="fulltext_xml" content="https://www.mdpi.com/2073-4425/10/9/633/xml"> <meta name="citation_xml_url" content="https://www.mdpi.com/2073-4425/10/9/633/xml"> <meta name="twitter:card" content="summary" /> <meta name="twitter:site" content="@MDPIOpenAccess" /> <meta name="twitter:image" content="https://pub.mdpi-res.com/img/journals/genes-logo-social.png?8600e93ff98dbf14" /> <meta property="fb:app_id" content="131189377574"/> <meta property="og:site_name" content="MDPI"/> <meta property="og:type" content="article"/> <meta property="og:url" content="https://www.mdpi.com/2073-4425/10/9/633" /> <meta property="og:title" content="One NF1 Mutation may Conceal Another" /> <meta property="og:description" content="Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with complete penetrance but high variable expressivity. NF1 is caused by loss-of-function mutations in the NF1 gene, a negative regulator of the RAS-MAPK pathway. The NF1 gene has one of the highest mutation rates in human disorders, which may explain the outbreak of independent de novo variants in the same family. Here, we report the co-occurrence of pathogenic variants in the NF1 and SPRED1 genes in six families with NF1 and Legius syndrome, using next-generation sequencing. In five of these families, we observed the co-occurrence of two independent NF1 variants. All NF1 variants were classified as pathogenic, according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines. In the sixth family, one sibling inherited a complete deletion of the NF1 gene from her mother and carried a variant of unknown significance in the SPRED1 gene. This variant was also present in her brother, who was diagnosed with Legius syndrome, a differential diagnosis of NF1. This work illustrates the complexity of molecular diagnosis in a not-so-rare genetic disease." /> <meta property="og:image" content="https://pub.mdpi-res.com/genes/genes-10-00633/article_deploy/html/images/genes-10-00633-g001-550.jpg?1566464953" /> <link rel="alternate" type="application/rss+xml" title="MDPI Publishing - Latest articles" href="https://www.mdpi.com/rss"> <meta name="google-site-verification" content="PxTlsg7z2S00aHroktQd57fxygEjMiNHydKn3txhvwY"> <meta name="facebook-domain-verification" content="mcoq8dtq6sb2hf7z29j8w515jjoof7" /> <script id="Cookiebot" data-cfasync="false" src="https://consent.cookiebot.com/uc.js" data-cbid="51491ddd-fe7a-4425-ab39-69c78c55829f" type="text/javascript" async></script>  <script type="text/plain" data-cookieconsent="statistics"> (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start': new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0], j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src= 'https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f); 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</ul> </div> <li> <a class="expand" onclick='$(this).closest("li").next("div").toggle(); return false;'>on Google Scholar</a> </li> <div id="AuthorGoogleExpand" style="display:none;"> <ul class="submenu"> <li class="li-link"> <a href="https://scholar.google.com/scholar?q=Laurence%20Pacot" target="_blank" rel="noopener noreferrer">Pacot, L.</a> <li> </li> <li class="li-link"> <a href="https://scholar.google.com/scholar?q=Cyril%20Burin%20des%20Roziers" target="_blank" rel="noopener noreferrer">Burin des Roziers, C.</a> <li> </li> <li class="li-link"> <a href="https://scholar.google.com/scholar?q=Ingrid%20Laurendeau" target="_blank" rel="noopener noreferrer">Laurendeau, I.</a> <li> </li> <li class="li-link"> <a href="https://scholar.google.com/scholar?q=Audrey%20Briand-Suleau" target="_blank" rel="noopener noreferrer">Briand-Suleau, A.</a> <li> </li> <li class="li-link"> <a href="https://scholar.google.com/scholar?q=Audrey%20Coustier" target="_blank" rel="noopener noreferrer">Coustier, A.</a> <li> </li> <li class="li-link"> <a href="https://scholar.google.com/scholar?q=Th%C3%A9odora%20Mayard" target="_blank" rel="noopener noreferrer">Mayard, T.</a> <li> </li> <li class="li-link"> <a href="https://scholar.google.com/scholar?q=Camille%20Tlemsani" target="_blank" rel="noopener noreferrer">Tlemsani, C.</a> <li> </li> <li class="li-link"> <a href="https://scholar.google.com/scholar?q=Laurence%20Faivre" target="_blank" rel="noopener noreferrer">Faivre, L.</a> <li> </li> <li class="li-link"> <a href="https://scholar.google.com/scholar?q=Quentin%20Thomas" target="_blank" rel="noopener noreferrer">Thomas, Q.</a> <li> </li> <li class="li-link"> <a href="https://scholar.google.com/scholar?q=Diana%20Rodriguez" target="_blank" rel="noopener noreferrer">Rodriguez, D.</a> <li> </li> <li class="li-link"> <a href="https://scholar.google.com/scholar?q=Sophie%20Blesson" target="_blank" rel="noopener noreferrer">Blesson, S.</a> <li> </li> <li class="li-link"> <a 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articletype">Article</span></div> <h1 class="title hypothesis_container" itemprop="name"> One <span class="html-italic">NF1</span> Mutation may Conceal Another </h1> <div class="art-authors hypothesis_container"> by <span class="inlineblock "><div class='profile-card-drop' data-dropdown='profile-card-drop2044460' data-options='is_hover:true, hover_timeout:5000'> Laurence Pacot</div><div id="profile-card-drop2044460" data-dropdown-content class="f-dropdown content profile-card-content" aria-hidden="true" tabindex="-1"><div class="profile-card__title"><div class="sciprofiles-link" style="display: inline-block"><div class="sciprofiles-link__link"><img class="sciprofiles-link__image" src="/bundles/mdpisciprofileslink/img/unknown-user.png" style="width: auto; height: 16px; border-radius: 50%;"><span class="sciprofiles-link__name">Laurence Pacot</span></div></div></div><div class="profile-card__buttons" style="margin-bottom: 10px;"><a href="https://sciprofiles.com/profile/796425?utm_source=mdpi.com&utm_medium=website&utm_campaign=avatar_name" class="button button--color-inversed" target="_blank"> SciProfiles </a><a href="https://scilit.com/scholars?q=Laurence%20Pacot" class="button button--color-inversed" target="_blank"> Scilit </a><a href="https://www.preprints.org/search?search1=Laurence%20Pacot&field1=authors" class="button button--color-inversed" target="_blank"> Preprints.org </a><a href="https://scholar.google.com/scholar?q=Laurence%20Pacot" class="button button--color-inversed" target="_blank" rels="noopener noreferrer"> Google Scholar </a></div></div><sup> 1,2</sup>, </span><span class="inlineblock "><div class='profile-card-drop' data-dropdown='profile-card-drop2044461' data-options='is_hover:true, hover_timeout:5000'> Cyril Burin des Roziers</div><div id="profile-card-drop2044461" data-dropdown-content class="f-dropdown content profile-card-content" aria-hidden="true" tabindex="-1"><div class="profile-card__title"><div class="sciprofiles-link" style="display: inline-block"><div class="sciprofiles-link__link"><img class="sciprofiles-link__image" src="/bundles/mdpisciprofileslink/img/unknown-user.png" style="width: auto; height: 16px; border-radius: 50%;"><span class="sciprofiles-link__name">Cyril Burin des Roziers</span></div></div></div><div class="profile-card__buttons" style="margin-bottom: 10px;"><a href="https://sciprofiles.com/profile/author/SUxJaXAwWklYcThQeTBTMUpzenYrZDhMMjdSMElML2NyOEhkK0FmWlQ4cz0=?utm_source=mdpi.com&utm_medium=website&utm_campaign=avatar_name" class="button button--color-inversed" target="_blank"> SciProfiles </a><a href="https://scilit.com/scholars?q=Cyril%20Burin%20des%20Roziers" class="button button--color-inversed" target="_blank"> Scilit </a><a href="https://www.preprints.org/search?search1=Cyril%20Burin%20des%20Roziers&field1=authors" class="button button--color-inversed" target="_blank"> Preprints.org </a><a href="https://scholar.google.com/scholar?q=Cyril%20Burin%20des%20Roziers" class="button button--color-inversed" target="_blank" rels="noopener noreferrer"> Google Scholar </a></div></div><sup> 1,2</sup><a href="https://orcid.org/0000-0001-9720-5536" target="_blank" rel="noopener noreferrer"><img src="https://pub.mdpi-res.com/img/design/orcid.png?0465bc3812adeb52?1739526160" title="ORCID" style="position: relative; width: 13px; margin-left: 3px; max-width: 13px !important; height: auto; top: -5px;"></a>, </span><span class="inlineblock "><div class='profile-card-drop' data-dropdown='profile-card-drop2044462' data-options='is_hover:true, hover_timeout:5000'> Ingrid Laurendeau</div><div id="profile-card-drop2044462" data-dropdown-content class="f-dropdown content profile-card-content" aria-hidden="true" tabindex="-1"><div class="profile-card__title"><div class="sciprofiles-link" style="display: inline-block"><div class="sciprofiles-link__link"><img class="sciprofiles-link__image" src="/bundles/mdpisciprofileslink/img/unknown-user.png" style="width: auto; height: 16px; border-radius: 50%;"><span class="sciprofiles-link__name">Ingrid Laurendeau</span></div></div></div><div class="profile-card__buttons" style="margin-bottom: 10px;"><a href="https://sciprofiles.com/profile/author/Zjd3Y21LakU4K3NhRVMrSzVpODN0WklFN2E4d29kd255eVNFM2pvN3NOMXVHMEwzTEdNaitRYUVXU3Fxd3pkUg==?utm_source=mdpi.com&utm_medium=website&utm_campaign=avatar_name" class="button button--color-inversed" target="_blank"> SciProfiles </a><a href="https://scilit.com/scholars?q=Ingrid%20Laurendeau" class="button button--color-inversed" target="_blank"> Scilit </a><a href="https://www.preprints.org/search?search1=Ingrid%20Laurendeau&field1=authors" class="button button--color-inversed" target="_blank"> Preprints.org </a><a href="https://scholar.google.com/scholar?q=Ingrid%20Laurendeau" class="button button--color-inversed" target="_blank" rels="noopener noreferrer"> Google Scholar </a></div></div><sup> 2</sup>, </span><span class="inlineblock "><div class='profile-card-drop' data-dropdown='profile-card-drop2044463' data-options='is_hover:true, hover_timeout:5000'> Audrey Briand-Suleau</div><div id="profile-card-drop2044463" data-dropdown-content class="f-dropdown content profile-card-content" aria-hidden="true" tabindex="-1"><div class="profile-card__title"><div class="sciprofiles-link" style="display: inline-block"><div class="sciprofiles-link__link"><img class="sciprofiles-link__image" src="/bundles/mdpisciprofileslink/img/unknown-user.png" style="width: auto; height: 16px; border-radius: 50%;"><span class="sciprofiles-link__name">Audrey Briand-Suleau</span></div></div></div><div class="profile-card__buttons" style="margin-bottom: 10px;"><a href="https://sciprofiles.com/profile/author/YmFMYWlQWHd1R1dxTGpGcDBRdFNlZ0xwSmdwbVVSTCt1QlFMcFFFMUdkST0=?utm_source=mdpi.com&utm_medium=website&utm_campaign=avatar_name" class="button button--color-inversed" target="_blank"> SciProfiles </a><a 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src="/bundles/mdpisciprofileslink/img/unknown-user.png" style="width: auto; height: 16px; border-radius: 50%;"><span class="sciprofiles-link__name">Audrey Coustier</span></div></div></div><div class="profile-card__buttons" style="margin-bottom: 10px;"><a href="https://sciprofiles.com/profile/author/NmNxQlljTU1KR1JIUmxVZmVEN1dvQjZKamVMeWhvMzRyckhRRDVwaXMxND0=?utm_source=mdpi.com&utm_medium=website&utm_campaign=avatar_name" class="button button--color-inversed" target="_blank"> SciProfiles </a><a href="https://scilit.com/scholars?q=Audrey%20Coustier" class="button button--color-inversed" target="_blank"> Scilit </a><a href="https://www.preprints.org/search?search1=Audrey%20Coustier&field1=authors" class="button button--color-inversed" target="_blank"> Preprints.org </a><a href="https://scholar.google.com/scholar?q=Audrey%20Coustier" class="button button--color-inversed" target="_blank" rels="noopener noreferrer"> Google Scholar </a></div></div><sup> 1</sup>, </span><span class="inlineblock "><div class='profile-card-drop' data-dropdown='profile-card-drop2044465' data-options='is_hover:true, hover_timeout:5000'> Théodora Mayard</div><div id="profile-card-drop2044465" data-dropdown-content class="f-dropdown content profile-card-content" aria-hidden="true" tabindex="-1"><div class="profile-card__title"><div class="sciprofiles-link" style="display: inline-block"><div class="sciprofiles-link__link"><img class="sciprofiles-link__image" src="/bundles/mdpisciprofileslink/img/unknown-user.png" style="width: auto; height: 16px; border-radius: 50%;"><span class="sciprofiles-link__name">Théodora Mayard</span></div></div></div><div class="profile-card__buttons" style="margin-bottom: 10px;"><a href="https://sciprofiles.com/profile/author/di9jemxIbUtMd0pqd0pBS0JBWmxGOHZYb3Vxa3hqR2lFVTc2OC9rRmpWMD0=?utm_source=mdpi.com&utm_medium=website&utm_campaign=avatar_name" class="button button--color-inversed" target="_blank"> SciProfiles </a><a 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src="/bundles/mdpisciprofileslink/img/unknown-user.png" style="width: auto; height: 16px; border-radius: 50%;"><span class="sciprofiles-link__name">Camille Tlemsani</span></div></div></div><div class="profile-card__buttons" style="margin-bottom: 10px;"><a href="https://sciprofiles.com/profile/782225?utm_source=mdpi.com&utm_medium=website&utm_campaign=avatar_name" class="button button--color-inversed" target="_blank"> SciProfiles </a><a href="https://scilit.com/scholars?q=Camille%20Tlemsani" class="button button--color-inversed" target="_blank"> Scilit </a><a href="https://www.preprints.org/search?search1=Camille%20Tlemsani&field1=authors" class="button button--color-inversed" target="_blank"> Preprints.org </a><a href="https://scholar.google.com/scholar?q=Camille%20Tlemsani" class="button button--color-inversed" target="_blank" rels="noopener noreferrer"> Google Scholar </a></div></div><sup> 1,2</sup><a href="https://orcid.org/0000-0002-3342-1704" target="_blank" rel="noopener noreferrer"><img src="https://pub.mdpi-res.com/img/design/orcid.png?0465bc3812adeb52?1739526160" title="ORCID" style="position: relative; width: 13px; margin-left: 3px; max-width: 13px !important; height: auto; top: -5px;"></a>, </span><span class="inlineblock "><div class='profile-card-drop' data-dropdown='profile-card-drop2044467' data-options='is_hover:true, hover_timeout:5000'> Laurence Faivre</div><div id="profile-card-drop2044467" data-dropdown-content class="f-dropdown content profile-card-content" aria-hidden="true" tabindex="-1"><div class="profile-card__title"><div class="sciprofiles-link" style="display: inline-block"><div class="sciprofiles-link__link"><img class="sciprofiles-link__image" src="/bundles/mdpisciprofileslink/img/unknown-user.png" style="width: auto; height: 16px; border-radius: 50%;"><span class="sciprofiles-link__name">Laurence Faivre</span></div></div></div><div class="profile-card__buttons" style="margin-bottom: 10px;"><a href="https://sciprofiles.com/profile/author/YzdrSXFpZUxCN0Y5WEFpd3laVHFLU3ZvWlZLTGVyV2g1a1owNWNFLzRvZz0=?utm_source=mdpi.com&utm_medium=website&utm_campaign=avatar_name" class="button button--color-inversed" target="_blank"> SciProfiles </a><a href="https://scilit.com/scholars?q=Laurence%20Faivre" class="button button--color-inversed" target="_blank"> Scilit </a><a href="https://www.preprints.org/search?search1=Laurence%20Faivre&field1=authors" class="button button--color-inversed" target="_blank"> Preprints.org </a><a href="https://scholar.google.com/scholar?q=Laurence%20Faivre" class="button button--color-inversed" target="_blank" rels="noopener noreferrer"> Google Scholar </a></div></div><sup> 3,4</sup>, </span><span class="inlineblock "><div class='profile-card-drop' data-dropdown='profile-card-drop2044468' data-options='is_hover:true, hover_timeout:5000'> Quentin Thomas</div><div id="profile-card-drop2044468" data-dropdown-content class="f-dropdown content profile-card-content" aria-hidden="true" tabindex="-1"><div class="profile-card__title"><div class="sciprofiles-link" style="display: inline-block"><div class="sciprofiles-link__link"><img class="sciprofiles-link__image" src="/bundles/mdpisciprofileslink/img/unknown-user.png" style="width: auto; height: 16px; border-radius: 50%;"><span class="sciprofiles-link__name">Quentin Thomas</span></div></div></div><div class="profile-card__buttons" style="margin-bottom: 10px;"><a href="https://sciprofiles.com/profile/4037166?utm_source=mdpi.com&utm_medium=website&utm_campaign=avatar_name" class="button button--color-inversed" target="_blank"> SciProfiles </a><a href="https://scilit.com/scholars?q=Quentin%20Thomas" class="button button--color-inversed" target="_blank"> Scilit </a><a href="https://www.preprints.org/search?search1=Quentin%20Thomas&field1=authors" class="button button--color-inversed" target="_blank"> Preprints.org </a><a href="https://scholar.google.com/scholar?q=Quentin%20Thomas" class="button 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href="/cdn-cgi/l/email-protection#79561a171d541a1e105615561c1418101554090b160d1c1a0d1016175a4949484e4f4c491a494f4d1b484c494d484f4941494d491b48484b4c484c494d484e491a484f49484949484f494f494d484e48484949484f4d1b494a484e"><sup><i class="fa fa-envelope-o"></i></sup></a><a href="https://orcid.org/0000-0002-1881-8762" target="_blank" rel="noopener noreferrer"><img src="https://pub.mdpi-res.com/img/design/orcid.png?0465bc3812adeb52?1739526160" title="ORCID" style="position: relative; width: 13px; margin-left: 3px; max-width: 13px !important; height: auto; top: -5px;"></a></span><a href="#" class="show-full-author-list"><i class="material-icons">add</i> Show full author list </a><a href="#" class="hide-full-author-list"><i class="material-icons">remove</i> Hide full author list </a> </div> <div class="nrm"></div> <span style="display:block; height:6px;"></span> <div></div> <div style="margin: 5px 0 15px 0;" class="hypothesis_container"> <div class="art-affiliations"> <div class="affiliation "> <div class="affiliation-item"><sup>1</sup></div> <div class="affiliation-name affiliation-name-extended">Service de Génétique et Biologie Moléculaires, Hôpital Cochin, HUPC, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France</div> </div> <div class="affiliation "> <div class="affiliation-item"><sup>2</sup></div> <div class="affiliation-name affiliation-name-extended">Institut Cochin, INSERM U1016, Université Paris Descartes, 75014 Paris, France</div> </div> <div class="affiliation "> <div class="affiliation-item"><sup>3</sup></div> <div class="affiliation-name affiliation-name-extended">Inserm, UMR 1231, Génétique des Anomalies du Développement, Université de Bourgogne, 21079 Dijon, France</div> </div> <div class="affiliation "> <div class="affiliation-item"><sup>4</sup></div> <div class="affiliation-name affiliation-name-extended">Centre de Référence Anomalies du Développement et Syndromes Malformatifs, Hôpital d’Enfants, 21079 Dijon, France</div> </div> <div class="affiliation "> <div class="affiliation-item"><sup>5</sup></div> <div class="affiliation-name affiliation-name-extended">Department of Child Neurology and National Reference Center for Neurogenetic Disorders, Armand Trousseau Hospital, GHUEP, AP-HP, INSERM U1141, 75012 Paris, France</div> </div> <div class="affiliation "> <div class="affiliation-item"><sup>6</sup></div> <div class="affiliation-name affiliation-name-extended">GRC n°19 ConCer-LD, Sorbonne Université, 75012 Paris, France</div> </div> <div class="affiliation "> <div class="affiliation-item"><sup>7</sup></div> <div class="affiliation-name affiliation-name-extended">Service de Génétique, CHRU de Tours, 37044 Tours, France</div> </div> <div class="affiliation "> <div class="affiliation-item"><sup>8</sup></div> <div class="affiliation-name affiliation-name-extended">Centre de référence pour les Affections Rares en Génétique Ophtalmologique (CARGO), Hôpital Civil, 67091 Strasbourg, France</div> </div> <div class="affiliation "> <div class="affiliation-item"><sup>9</sup></div> <div class="affiliation-name affiliation-name-extended">Service de Génétique Médicale, Hôpital de Hautepierre, 67200 Strasbourg, France</div> </div> <div class="affiliation "> <div class="affiliation-item"><sup>10</sup></div> <div class="affiliation-name affiliation-name-extended">Laboratoire de Génétique Médicale, INSERM U1112, 67000 Strasbourg, France</div> </div> <div class="affiliation affiliation-item-hidden js-affiliation-item-hidden"> <div class="affiliation-item"><sup>11</sup></div> <div class="affiliation-name affiliation-name-extended">Service de Génétique, EA3808, Université de Poitiers, CHU de Poitiers, 86000 Poitiers, France</div> </div> <div class="affiliation affiliation-item-hidden js-affiliation-item-hidden"> <div class="affiliation-item"><sup>12</sup></div> <div class="affiliation-name affiliation-name-extended">Department of Cytogenetics and clinical genetics, Limoges University Hospital, 87042 Limoges, France</div> </div> <div class="affiliation affiliation-item-hidden js-affiliation-item-hidden"> <div class="affiliation-item"><sup>13</sup></div> <div class="affiliation-name affiliation-name-extended">UMR 7252, Limoges University, CNRS, XLIM, 87000 Limoges, France</div> </div> <div class="affiliation affiliation-item-hidden js-affiliation-item-hidden"> <div class="affiliation-item"><sup>14</sup></div> <div class="affiliation-name affiliation-name-extended">EA 4537, Antilles University, 97261 Fort-de-France, Martinique, France</div> </div> <div class="affiliation affiliation-item-hidden js-affiliation-item-hidden"> <div class="affiliation-item"><sup>15</sup></div> <div class="affiliation-name affiliation-name-extended">DRCI, Martinique University Hospital, 97261 Fort-de-France, Martinique, France</div> </div> <div class="affiliation"> <a href="#" class="show-full-affiliation-list"> <div class="affiliation-item"><sup> </sup></div> <div class="affiliation-name affiliation-name-extended"> <i class="material-icons">add</i> Show full affiliation list </div> </a> <a href="#" class="hide-full-affiliation-list"> <div class="affiliation-item"><sup> </sup></div> <div class="affiliation-name affiliation-name-extended"> <i class="material-icons">remove</i> Hide full affiliation list </div> </a> </div> <div class="affiliation"> <div class="affiliation-item"><sup>*</sup></div> <div class="affiliation-name affiliation-name-extended">Author to whom correspondence should be addressed. </div> </div> </div> </div> <div class="bib-identity" style="margin-bottom: 10px;"> <em>Genes</em> <b>2019</b>, <em>10</em>(9), 633; <a href="https://doi.org/10.3390/genes10090633">https://doi.org/10.3390/genes10090633</a> </div> <div class="pubhistory" style="font-weight: bold; padding-bottom: 10px;"> <span style="display: inline-block">Submission received: 19 July 2019</span> / <span style="display: inline-block">Revised: 10 August 2019</span> / <span style="display: inline-block">Accepted: 20 August 2019</span> / <span style="display: inline-block">Published: 22 August 2019</span> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Special Issue <a href=" /journal/genes/special_issues/neurofibromatosis ">Neurofibromatosis 1 Genetics</a>)<br/> </div> <div class="highlight-box1"> <div class="download"> <a class="button button--color-inversed button--drop-down" data-dropdown="drop-download-259901" aria-controls="drop-supplementary-259901" aria-expanded="false"> Download <i class="material-icons">keyboard_arrow_down</i> </a> <div id="drop-download-259901" class="f-dropdown label__btn__dropdown label__btn__dropdown--button" data-dropdown-content aria-hidden="true" tabindex="-1"> <a class="UD_ArticlePDF" href="/2073-4425/10/9/633/pdf?version=1566464889" data-name="One NF1 Mutation may Conceal Another" data-journal="genes">Download PDF</a> <br/> <a id="js-pdf-with-cover-access-captcha" href="#" data-target="/2073-4425/10/9/633/pdf-with-cover" class="accessCaptcha">Download PDF with Cover</a> <br/> <a id="js-xml-access-captcha" href="#" data-target="/2073-4425/10/9/633/xml" class="accessCaptcha">Download XML</a> <br/> <a href="/2073-4425/10/9/633/epub" id="epub_link">Download Epub</a> <br/> </div> <div class="js-browse-figures" style="display: inline-block;"> <a href="#" class="button button--color-inversed margin-bottom-10 openpopupgallery UI_BrowseArticleFigures" data-target='article-popup' data-counterslink = "https://www.mdpi.com/2073-4425/10/9/633/browse" >Browse Figure</a> </div> <div id="article-popup" class="popupgallery" style="display: inline; line-height: 200%"> <a href="https://pub.mdpi-res.com/genes/genes-10-00633/article_deploy/html/images/genes-10-00633-g001.png?1566464953" title=" <strong>Figure 1</strong><br/> <p>Pedigrees of the six NF1 families. NF1 patients with molecular diagnosis, relatives reported as presenting a NF1 phenotype, and patients with a Legius syndrome are shown in black, black crosshatching, and gray, respectively. Haplotypes for the <span class="html-italic">NF1</span> and <span class="html-italic">SPRED1</span> loci are depicted for the corresponding patients. Arrows indicate the propositus in each family. Paternal and maternal ages at conception are indicated above the patient in blue and red, respectively, when available.</p> "> </a> </div> <a class="button button--color-inversed" href="/2073-4425/10/9/633/notes">Versions Notes</a> </div> </div> <div class="responsive-moving-container small hidden" data-id="article-counters" style="margin-top: 15px;"></div> <div class="html-dynamic"> <section> <div class="art-abstract art-abstract-new in-tab hypothesis_container"> <p> <div><section class="html-abstract" id="html-abstract"> <h2 id="html-abstract-title">Abstract</h2><b>:</b> <div class="html-p">Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with complete penetrance but high variable expressivity. NF1 is caused by loss-of-function mutations in the <span class="html-italic">NF1</span> gene, a negative regulator of the RAS-MAPK pathway. The <span class="html-italic">NF1</span> gene has one of the highest mutation rates in human disorders, which may explain the outbreak of independent de novo variants in the same family. Here, we report the co-occurrence of pathogenic variants in the <span class="html-italic">NF1</span> and <span class="html-italic">SPRED1</span> genes in six families with NF1 and Legius syndrome, using next-generation sequencing. In five of these families, we observed the co-occurrence of two independent <span class="html-italic">NF1</span> variants. All <span class="html-italic">NF1</span> variants were classified as pathogenic, according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines. In the sixth family, one sibling inherited a complete deletion of the <span class="html-italic">NF1</span> gene from her mother and carried a variant of unknown significance in the <span class="html-italic">SPRED1</span> gene. This variant was also present in her brother, who was diagnosed with Legius syndrome, a differential diagnosis of NF1. This work illustrates the complexity of molecular diagnosis in a not-so-rare genetic disease.</div> </section> <div id="html-keywords"> <div class="html-gwd-group"><div id="html-keywords-title">Keywords: </div><a href="/search?q=de+novo+variant">de novo variant</a>; <a href="/search?q=Legius+syndrome">Legius syndrome</a>; <a href="/search?q=neurofibromatosis+type+1">neurofibromatosis type 1</a>; <a href="/search?q=NF1"><span class="html-italic">NF1</span></a>; <a href="/search?q=SPRED1"><span class="html-italic">SPRED1</span></a></div> <div> </div> </div> </div> </p> </div> </section> </div> <div class="hypothesis_container"> <ul class="menu html-nav" data-prev-node="#html-quick-links-title"> </ul> <div class="html-body"> <section id='sec1-genes-10-00633' type='intro'><h2 data-nested='1'> 1. Introduction</h2><div class='html-p'>Neurofibromatosis type 1 (NF1; MIM#162200) is an autosomal dominant disease with a worldwide incidence between 1 in 2500 and 1 in 3000 individuals [<a href="#B1-genes-10-00633" class="html-bibr">1</a>]. Clinical features predominantly consist of multiple café-au-lait spots (CALS), axillary or inguinal freckling, Lisch nodules, and neurofibromas (NFs). Other symptoms can develop in some patients, such as optic pathway gliomas (OPGs), short stature, or pseudarthrosis. Affected patients are predisposed to benign peripheral nervous tumors [<a href="#B2-genes-10-00633" class="html-bibr">2</a>] called plexiform neurofibromas (PNFs), which can transform into malignant peripheral nerve sheath tumors (MPNSTs) in ~10% of cases [<a href="#B3-genes-10-00633" class="html-bibr">3</a>]. The NF1 diagnosis relies on the National Institutes of Health (NIH) clinical criteria [<a href="#B4-genes-10-00633" class="html-bibr">4</a>]. NF1 is characterized by complete penetrance and great inter- and intrafamilial variable expressivity [<a href="#B5-genes-10-00633" class="html-bibr">5</a>].</div><div class='html-p'>More than 95% of NF1 cases [<a href="#B6-genes-10-00633" class="html-bibr">6</a>] are caused by loss-of-function mutations in the <span class='html-italic'>NF1</span> gene (MIM*613113), which is located at 17q11.2. <span class='html-italic'>NF1</span> comprises 57 constitutive and three alternative exons and spans over ~350 kb. The 8454-nucleotide open reading frame of the <span class='html-italic'>NF1</span> gene (NM_00267.3) encodes a 2818-amino-acid protein, neurofibromin, which shows tumor suppressor function [<a href="#B7-genes-10-00633" class="html-bibr">7</a>] by negatively regulating the RAS-MAPK pathway [<a href="#B8-genes-10-00633" class="html-bibr">8</a>]. The <span class='html-italic'>NF1</span> gene shows one of the highest mutation rates [<a href="#B9-genes-10-00633" class="html-bibr">9</a>], with more than 2600 different pathogenic variants referenced in public databases (Leiden Open Variation Database and Human Gene Mutation Database). About 50% of all NF1 cases are sporadic, i.e., due to de novo mutations [<a href="#B10-genes-10-00633" class="html-bibr">10</a>,<a href="#B11-genes-10-00633" class="html-bibr">11</a>,<a href="#B12-genes-10-00633" class="html-bibr">12</a>].</div><div class='html-p'>Some of the NF1 clinical features are common to other diseases, such as Legius syndrome (MIM#611431), an autosomal dominant disorder characterized by the presence of multiple CALS, sometimes associated with skinfold freckling and macrocephaly or learning disabilities. Legius syndrome is caused by loss-of-function mutations in the <span class='html-italic'>SPRED1</span> gene (MIM*609291) [<a href="#B13-genes-10-00633" class="html-bibr">13</a>,<a href="#B14-genes-10-00633" class="html-bibr">14</a>,<a href="#B15-genes-10-00633" class="html-bibr">15</a>]. The SPRED1 protein acts as a negative regulator of the RAS-MAPK pathway [<a href="#B16-genes-10-00633" class="html-bibr">16</a>].</div><div class='html-p'>Here, we report the observation of six NF1 families. Surprisingly, the <span class='html-italic'>NF1</span> pathogenic variant identified in the index cases was not present in all the other affected members of the family, thus revealing the presence of a second independent <span class='html-italic'>NF1</span> pathogenic variant in the same family. In one family, NF1 and Legius syndrome co-occurred in siblings, challenging the molecular diagnosis for these patients. Our study aimed at highlighting the complexity of molecular diagnosis in NF1 families where patients can carry distinct pathogenic variants or may present with phenocopies.</div></section><section id='sec2-genes-10-00633' type=''><h2 data-nested='1'> 2. Materials and Methods</h2><section id='sec2dot1-genes-10-00633' type=''><h4 class='html-italic' data-nested='2'> 2.1. Study Samples</h4><div class='html-p'>Informed consent was collected for all the patients and their relatives (ethical approval code: <span class='html-italic'>Comités de protection des personnes</span> CPP17/79, A0296746, and 2015-08-11DC). Samples were collected on EDTA tubes for DNA analysis and on PAXgene™ Blood RNA Tubes (Becton Dickinson, Rungis, France) for RNA analysis. All patients underwent a physical examination with a referent clinician who recorded the phenotypic data according to a standardized questionnaire including: number and size of CALS; number and localization of freckling; number and localization of plexiform and spinal neurofibromas; number of cutaneous and subcutaneous neurofibromas, each classified into quantitative categories of 0, 1–9, 10–99, and >100; the presence or absence of MPNSTs, Lisch nodules, optic pathway gliomas, skeletal malformations, or developmental delay.</div></section><section id='sec2dot2-genes-10-00633' type=''><h4 class='html-italic' data-nested='2'> 2.2. DNA and RNA Extractions</h4><div class='html-p'>DNA extraction was performed with the Maxwell<sup>®</sup> 16 LEV Blood DNA Kit (Promega, Charbonnières-les-Bains, France) on EDTA blood samples according to the manufacturer’s instructions. RNA was directly extracted from 5 mL of PAXgene<sup>TM</sup> blood samples with the PAXgene<sup>TM</sup> Blood RNA System (Qiagen, Courtaboeuf, France) according to the manufacturer’s instructions. DNA concentrations were quantified using a NanoDrop 1000 Spectrophotometer v3.8 (Thermo Fisher Scientific, Courtaboeuf, France).</div></section><section id='sec2dot3-genes-10-00633' type=''><h4 class='html-italic' data-nested='2'> 2.3. Microsatellite Typing</h4><div class='html-p'>Four <span class='html-italic'>NF1</span> intragenic polymorphic microsatellites (D17S1307, D17S2163, D17S1166, and GDB:270136) were studied for segregation analysis. Three additional <span class='html-italic'>NF1</span> extragenic polymorphic microsatellites (D17S841, D17S1800, and D17S798) were also genotyped when the previous ones were not informative. Three <span class='html-italic'>SPRED1</span> intragenic polymorphic microsatellites were studied for family 6 (19AT, 19TG, 23AC). DNA samples were diluted to a concentration of 10 ng/mL and amplified using dedicated primers and the Taq GOLD polymerase (Thermo Fisher Scientific). The GS-500LIZ (Thermo Fisher Scientific) marker was used for detection. Sequencing analysis was performed on an ABI Prism 3130 automatic DNA sequencer (Thermo Fisher Scientific). The results were analyzed with the GeneMapper<sup>®</sup> v.4.0 software package (Thermo Fisher Scientific). Samples with a unique haplotype were tested for large <span class='html-italic'>NF1</span> deletion using real-time PCR-based gene dosage of exons 8 and 57, as described in Sabbagh et al., 2013 [<a href="#B6-genes-10-00633" class="html-bibr">6</a>]. To confirm that variants were de novo, both maternity and paternity were confirmed using a PowerPlex<sup>®</sup> 16 HS System (Promega, Madison, WI, USA) kit to analyze the segregation of 15 short tandem repeat (STR) markers.</div></section><section id='sec2dot4-genes-10-00633' type=''><h4 class='html-italic' data-nested='2'> 2.4. NF1 and SPRED1 Next-Generation Sequencing (NGS)</h4><div class='html-p'>Experiments were performed at the NGS facility of Cochin Hospital, Paris (Assistance Publique-Hôpitaux de Paris, France). The techniques were previously described by Pasmant et al., 2015 [<a href="#B17-genes-10-00633" class="html-bibr">17</a>]. Variants were analyzed with NextGENe v.2.4.2.2 (Softgenetics, State College, PA, USA) and Polydiag (Imagine Institute, Necker Hospital, Paris, France) software. </div></section><section id='sec2dot5-genes-10-00633' type=''><h4 class='html-italic' data-nested='2'> 2.5. DNA and RNA Sequencing with PCR</h4><div class='html-p'>Polymerase chain reaction (PCR) was performed either for screening purposes or for confirmation of NGS results on cDNA after reverse transcription of the <span class='html-italic'>NF1</span> transcript, or on DNA samples, respectively. Selected exons of the <span class='html-italic'>NF1</span> (NM_00267.3) and <span class='html-italic'>SPRED1</span> (NM_152594.2) genes were amplified by PCR and sequenced as previously described in Sabbagh et al., 2013 [<a href="#B6-genes-10-00633" class="html-bibr">6</a>]. Variants identified by cDNA or NGS approaches were confirmed using DNA sequencing analysis performed on the corresponding exon. Sequences were aligned on the reference sequence with Seqscape analysis software v2.5 (Thermo Fisher Scientific). </div></section><section id='sec2dot6-genes-10-00633' type=''><h4 class='html-italic' data-nested='2'> 2.6. Variant Classification</h4><div class='html-p'>Variants in the <span class='html-italic'>NF1</span> and <span class='html-italic'>SPRED1</span> genes are reported according to the reference sequences NM_00267.3 and NM_152594.2, respectively, with the first nucleotide of the first methionine codon corresponding to the +1 position. Exon numbering is indicated according to the NCBI nomenclature. Variants were named at the coding DNA and protein levels according to the Human Genome Variation Society (HGVS) recommendations. In silico predictions of the effect of missense variants were performed with SIFT, MutationTaster, and Polyphen-2, together with SpliceSiteFinder-like, MaxEntScan, NNSPLICE, GeneSplicer, and Human Splice Finder embedded in Alamut visual software v.2.7.1 (Interactive Biosoftware, Rouen, France). CADD scores were obtained for single nucleotide variants (SNVs) with the 1.4 version. Variant frequency in the general population was checked in the gnomAD and dbSNP databases. The Leiden Open Variation Database (LOVD) and ClinVar databases were systematically checked for all variants. An assessment of variants’ pathogenicity was performed according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines [<a href="#B18-genes-10-00633" class="html-bibr">18</a>]. </div></section></section><section id='sec3-genes-10-00633' type='results'><h2 data-nested='1'> 3. Results</h2><div class='html-p'>Pedigrees and clinical data of NF1 patients are shown in <a href="#genes-10-00633-f001" class="html-fig">Figure 1</a> and <a href="#genes-10-00633-t001" class="html-table">Table 1</a>, respectively. Ages at last examination are indicated in the corresponding column. All variants were classified according to the ACMG-AMP guidelines [<a href="#B18-genes-10-00633" class="html-bibr">18</a>] (<a href="#genes-10-00633-t002" class="html-table">Table 2</a>).</div><div class='html-p'>Family 1 is a Sephardic family in which two siblings (patients IV-1 and IV-3) were clinically diagnosed with NF1. The first child of the kindred (IV-1) had more than eight CALS >1.5 cm and five CALS <1.5 cm. He also had one subcutaneous NF on the right forearm, an anemic nevus on the left thigh, bilateral Lisch nodules, mild scoliosis, and learning disabilities with a global IQ of 105 at the age of 16. His sister (IV-3) had a Sylvian artery stroke when she was eight months old, leading to permanent left hemiparesis. She was diagnosed with NF1 as she had more than six CALS > 1.5 cm and multiple smaller CALS, bilateral axillary and inguinal freckling, cutaneous NFs, bilateral Lisch nodules, and mild scoliosis. The third child of the kindred (IV-2) suffered from intellectual disabilities, including reading delays. However, he did not show any sign of NF1. The family history revealed the existence of cysts in several relatives (eyelid cysts in III-7, head cysts in III-8, and renal cysts in III-10), but no formal diagnosis of NF1 was made in any of them. Molecular diagnosis in the two siblings IV-1 and IV-3 revealed two independent pathogenic variants in the <span class='html-italic'>NF1</span> gene: c.7084_7085insGA (p.Asn2362Argfs*14) and c.1885G>A (p.Gln616Glyfs*4), respectively. Sequencing of the parents’ DNA confirmed that both pathogenic variants occurred de novo. To determine the parental origin of each variant, long-range PCR was performed in the parents and children. Sequencing of the distal part of the intron 48 revealed the presence of the c.7126+37C>G variant in both the father (II-6) and his affected son (IV-1). This benign variant was in <span class='html-italic'>cis</span> with the c.7084_7085insGA pathogenic variant found in the affected son (IV-1), indicating that the de novo c.7084_7085insGA pathogenic variant occurred in the <span class='html-italic'>NF1</span> paternal allele.</div><div class='html-p'>Family 2 is a Caucasian family with a medical history of NF1 in the paternal branch. All the affected members of family 2 (patients I-2, II-1, III-2, and III-3) had more than six CALS. The grandmother, I-2, was also described as having developed a scalp tumor. The propositus (III-3) had a more severe clinical presentation including bilateral axillary freckling and Lisch nodules, OPG, multiple cutaneous and subcutaneous NFs, and a thoracic PNF. He also developed a spinal NF near the left iliac crest, xanthogranulomas, scoliosis, and suffered from attention deficit disorder. NGS revealed the presence of the c.4537C>T, p.(Arg1513*) pathogenic variant in the <span class='html-italic'>NF1</span> gene, which was confirmed at the transcript level. This variant was not found in the other affected members of the family. The grandmother (I-2), father (II-1), and sister (III-2) of the propositus carried the c.6642-5del pathogenic <span class='html-italic'>NF1</span> variant, which is responsible for the exon 45 skip in the <span class='html-italic'>NF1</span> transcript: p.Phe2215Hisfs*6.</div><div class='html-p'>In family 3, the propositus (patient III-2) presented with an OPG associated with CALS. NGS analysis in the propositus identified the c.2044C>T, p.(Gln682*) pathogenic variant in the <span class='html-italic'>NF1</span> gene. Her cousin (III-1) showed multiple CALS, bilateral sub-mammal freckling, cutaneous and subcutaneous NFs, one PNF, and scoliosis. Unidentified bright objects (UBOs) were revealed on MRI, but no OPG was identified. NGS and <span class='html-italic'>NF1</span> transcript analysis identified the c.5749+5G>A, p.Ser1850fs*2 pathogenic variant in the <span class='html-italic'>NF1</span> gene (leading to the exon 39 skip in the <span class='html-italic'>NF1</span> transcript). Parental DNA studies showed the de novo origin of both variants in patients III-1 and III-2. Segregation analysis revealed that the two patients inherited distinct NF1 haplotypes from their respective parents, suggesting that the two variants occurred on different alleles of the <span class='html-italic'>NF1</span> gene.</div><div class='html-p'>Family 4 is a Caucasian family with a medical history of NF1. The propositus (patient III-5) was a 39-year-old man presenting with CALS, bilateral axillary freckling, Lisch nodules, and cutaneous and subcutaneous neurofibromas. In addition to NF1, he also suffered from Brugada syndrome (MIM#601144), inherited from his father. NGS analysis of <span class='html-italic'>NF1</span> in patient III-5 revealed the c.3314+2T>C <span class='html-italic'>NF1</span> pathogenic variant, which was predicted by in silico tools to alter the <span class='html-italic'>NF1</span> transcript splicing. His cousin (patient III-2), a 26-year-old woman, was addressed for a molecular confirmation of her clinical NF1, including CALS, axillary freckling, and cutaneous NFs. NGS analysis revealed the c.5154dup, p.(Phe1719Ilefs*17) <span class='html-italic'>NF1</span> pathogenic variant in patient III-2. NF1 symptoms were mentioned in several members of the family, including their respective parents (patients II-3 and II-2), an aunt who died from a brain tumor (II-1), and her daughter (III-1).</div><div class='html-p'>The propositus of family 5 (patient II-6) was a 23-year-old girl with short stature (150 cm), multiple CALS, axillary freckling, cutaneous and subcutaneous NFs, one plexiform neurofibroma in the lumbar fossa, Lisch nodules, and scoliosis. She had developed breast cancer. NGS analysis identified the c.3916C>T, p.(Arg1306*) <span class='html-italic'>NF1</span> pathogenic variant. Her great-nephew (patient IV-1) was also diagnosed with NF1. He presented a unilateral OPG at the age of two. He suffered from pseudarthrosis and sphenoid wing dysplasia. He underwent multiple surgeries for a tibial deformation. Together with the classical manifestations of the disease, both patients II-6 and IV-1 showed UBOs on MRI. Patient IV-1 carried a different <span class='html-italic'>NF1</span> pathogenic variant from the propositus: c.2376del, p.Asn793Thrfs*28. Molecular analysis of the family showed that both <span class='html-italic'>NF1</span> variants occurred de novo. Of note, the father of the propositus (individual I-1) was described as affected by NF1 (presenting Lisch nodules and CALS), but he did not carry his daughter’s <span class='html-italic'>NF1</span> variant, nor any other <span class='html-italic'>NF1</span> variant that could have been detected by our techniques.</div><div class='html-p'>In family 6, both the mother (patient I-2) and the daughter (II-2) carried a large deletion of the <span class='html-italic'>NF1</span> locus. The 10-year-old propositus (II-2) presented multiple CALS, freckling, cutaneous NFs, and a cardiac malformation. Her mother (I-2) presented CALS, cutaneous NFs, and scoliosis. The propositus’ brother (II-1) only showed multiple CALS and freckling. No pathogenic variant or deletion of the <span class='html-italic'>NF1</span> gene could be detected in this patient. Real-time quantitative PCR was performed in all three patients and confirmed the absence of deletion at the <span class='html-italic'>NF1</span> locus for II-1. However, he and his sister both carried a variant of unknown significance in the <span class='html-italic'>SPRED1</span> gene: c.944C>T, p.(Pro315Leu). The variant was not detected in their mother, but their father could not be tested. The Pro315 is evolutionarily conserved and proline presents very different chemical and physical properties from leucine. The c.944C>T, p.(Pro315Leu) variant is rare in the global population (31/282544 alleles in gnomAD) and is predominantly found in the African population (30/24958).</div></section><section id='sec4-genes-10-00633' type='discussion'><h2 data-nested='1'> 4. Discussion</h2><div class='html-p'>Because of its great phenotypic and genetic heterogeneities, NF1 diagnosis can be challenging. To date, few cases of two or more different <span class='html-italic'>NF1</span> pathogenic variants in the same family have been described [<a href="#B6-genes-10-00633" class="html-bibr">6</a>,<a href="#B23-genes-10-00633" class="html-bibr">23</a>,<a href="#B24-genes-10-00633" class="html-bibr">24</a>]. Such cases are challenging and the absence of a familial mutation in a patient presenting with NF1 clinical features is not sufficient to exclude the diagnosis. On the contrary, the high mutation rate reported in the <span class='html-italic'>NF1</span> gene [<a href="#B9-genes-10-00633" class="html-bibr">9</a>] should encourage us to search for the occurrence of a de novo mutation in any suspected case.</div><div class='html-p'>Likewise, phenocopies in a family can lead to a delayed diagnosis. As mentioned above for family 6, Legius syndrome can be mistaken for NF1. The inability to find a <span class='html-italic'>NF1</span> pathogenic variant should encourage the exploration of the <span class='html-italic'>SPRED1</span> gene when confronted with a mild phenotype. In the case of family 6, the pathogenicity of the <span class='html-italic'>SPRED1</span> c.944C>T variant could not be ascertained. Its allelic frequency (31/282544 alleles in GnomAD, predominantly in the African population) and the lack of data about its de novo origin questioned its role in the development of CALS in patient II-1. The <span class='html-italic'>SPRED1</span> c.944C>T, p.(Pro315Leu) variant was thus classified as a variant of unknown significance according to the ACMG-AMP guidelines. Only one case of co-occurrence of NF1 and Legius syndrome in the same family (with confirmed pathogenic variants in the <span class='html-italic'>NF1</span> and <span class='html-italic'>SPRED1</span> genes) has previously been reported [<a href="#B25-genes-10-00633" class="html-bibr">25</a>]. Moreover, some <span class='html-italic'>NF1</span> mutations can lead to the development of the overlapping neurofibromatosis‒Noonan syndrome (MIM #601321) [<a href="#B26-genes-10-00633" class="html-bibr">26</a>,<a href="#B27-genes-10-00633" class="html-bibr">27</a>,<a href="#B28-genes-10-00633" class="html-bibr">28</a>,<a href="#B29-genes-10-00633" class="html-bibr">29</a>,<a href="#B30-genes-10-00633" class="html-bibr">30</a>,<a href="#B31-genes-10-00633" class="html-bibr">31</a>], which combines the typical features of NF1 (CALS, axillary and inguinal freckling, Lisch nodules, OPG, and neurofibromas) and Noonan syndrome (short stature, facial dysmorphism, and congenital heart defects, among others). This observation further reduces the gap between RASopathies and complicates genetic counseling, even more so when NF1 and Noonan syndrome co-exist in one family [<a href="#B32-genes-10-00633" class="html-bibr">32</a>,<a href="#B33-genes-10-00633" class="html-bibr">33</a>] or in one patient [<a href="#B34-genes-10-00633" class="html-bibr">34</a>,<a href="#B35-genes-10-00633" class="html-bibr">35</a>,<a href="#B36-genes-10-00633" class="html-bibr">36</a>].</div><div class='html-p'>Studies have suggested that most de novo point mutations or small indels have a paternal origin [<a href="#B37-genes-10-00633" class="html-bibr">37</a>], whereas large deletions are predominantly of maternal origin, as is the case with NF1 [<a href="#B38-genes-10-00633" class="html-bibr">38</a>]. Advanced paternal age can substantially increase this tendency for de novo point mutations, particularly for mutations occurring in genes implicated in the RAS pathway [<a href="#B39-genes-10-00633" class="html-bibr">39</a>,<a href="#B40-genes-10-00633" class="html-bibr">40</a>]. Indeed, such mutations stimulate selfish selection during spermatogenesis in a process close to oncogenesis, leading to an over-representation of spermatozoids carrying these alterations over time. The <span class='html-italic'>NF1</span> gene seems to obey this rule, too [<a href="#B41-genes-10-00633" class="html-bibr">41</a>,<a href="#B42-genes-10-00633" class="html-bibr">42</a>]. In the present cases, segregation analysis of family 5 showed that patient II-6 inherited her mutated allele from her father, as she transmitted her maternal chromosome to her children, who were not affected. In family 1, haplotype analysis indicated that the de novo c.7084_7085insGA pathogenic variant occurred in the <span class='html-italic'>NF1</span> paternal allele of patient IV-1. His father (III-6) was 35 years old at the time of conception.</div></section><section id='sec5-genes-10-00633' type='conclusions'><h2 data-nested='1'> 5. Conclusions</h2><div class='html-p'>These clinical reports highlight the primordial importance of a systematic approach to the clinical and molecular diagnoses of NF1 patients. Putative co-occurrence of two or more distinct <span class='html-italic'>NF1</span> mutations in a pedigree should not be underestimated.</div></section> </div> <div class="html-back"> <section class='html-notes'><h2 >Author Contributions</h2><div class='html-p'>Conceptualization, methodology and validation, B.P., M.V., D.V. and E.P.; software, A.B.-S.; technique, L.P., I.L., A.C., T.M., C.T.; investigation, L.P., L.F., Q.T., D.R., S.B., H.D., Y.-G.M., B.G.-D., C.Y., B.D., C.D.; writing-original draft preparation, L.P. and C.B.d.R.; writing-review and editing, L.P. and E.P.; supervision and project administration, E.P.</div></section><section class='html-notes'><h2 >Funding</h2><div class='html-p'>This research received no external funding.</div></section><section id='html-ack' class='html-ack'><h2 >Acknowledgments</h2><div class='html-p'>The authors are grateful to patients for their participation and cooperation.</div></section><section class='html-notes'><h2 >Conflicts of Interest</h2><div class='html-p'>The authors declare no conflict of interest.</div></section><section id='html-references_list'><h2>References</h2><ol class='html-xx'><li id='B1-genes-10-00633' class='html-x' data-content='1.'>Williams, V.C.; Lucas, J.; Babcock, M.A.; Gutmann, D.H.; Korf, B.; Maria, B.L. Neurofibromatosis type 1 revisited. <span class='html-italic'>Pediatrics</span> <b>2009</b>, <span class='html-italic'>123</span>, 124–133. [<a href="https://scholar.google.com/scholar_lookup?title=Neurofibromatosis+type+1+revisited&author=Williams,+V.C.&author=Lucas,+J.&author=Babcock,+M.A.&author=Gutmann,+D.H.&author=Korf,+B.&author=Maria,+B.L.&publication_year=2009&journal=Pediatrics&volume=123&pages=124%E2%80%93133&doi=10.1542/peds.2007-3204" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1542/peds.2007-3204" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B2-genes-10-00633' class='html-x' data-content='2.'>Ferner, R.E.; Huson, S.M.; Thomas, N.; Moss, C.; Willshaw, H.; Evans, D.G.; Upadhyaya, M.; Towers, R.; Gleeson, M.; Steiger, C.; et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. <span class='html-italic'>J. Med. Genet.</span> <b>2007</b>, <span class='html-italic'>44</span>, 81–88. [<a href="https://scholar.google.com/scholar_lookup?title=Guidelines+for+the+diagnosis+and+management+of+individuals+with+neurofibromatosis+1&author=Ferner,+R.E.&author=Huson,+S.M.&author=Thomas,+N.&author=Moss,+C.&author=Willshaw,+H.&author=Evans,+D.G.&author=Upadhyaya,+M.&author=Towers,+R.&author=Gleeson,+M.&author=Steiger,+C.&publication_year=2007&journal=J.+Med.+Genet.&volume=44&pages=81%E2%80%9388&doi=10.1136/jmg.2006.045906" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1136/jmg.2006.045906" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B3-genes-10-00633' class='html-x' data-content='3.'>Tucker, T.; Wolkenstein, P.; Revuz, J.; Zeller, J.; Friedman, J.M. Association between benign and malignant peripheral nerve sheath tumors in NF1. <span class='html-italic'>Neurology</span> <b>2005</b>, <span class='html-italic'>65</span>, 205–211. [<a href="https://scholar.google.com/scholar_lookup?title=Association+between+benign+and+malignant+peripheral+nerve+sheath+tumors+in+NF1&author=Tucker,+T.&author=Wolkenstein,+P.&author=Revuz,+J.&author=Zeller,+J.&author=Friedman,+J.M.&publication_year=2005&journal=Neurology&volume=65&pages=205%E2%80%93211&doi=10.1212/01.wnl.0000168830.79997.13" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1212/01.wnl.0000168830.79997.13" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B4-genes-10-00633' class='html-x' data-content='4.'>Stumpf, D.A. Neurofibromatosis. Conference statement. National Institutes of Health Consensus Development Conference. <span class='html-italic'>Arch. Neurol.</span> <b>1988</b>, <span class='html-italic'>45</span>, 575–578. [<a href="https://scholar.google.com/scholar_lookup?title=Neurofibromatosis.+Conference+statement.+National+Institutes+of+Health+Consensus+Development+Conference&author=Stumpf,+D.A.&publication_year=1988&journal=Arch.+Neurol.&volume=45&pages=575%E2%80%93578" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>]</li><li id='B5-genes-10-00633' class='html-x' data-content='5.'>Friedman, J.M. Epidemiology of neurofibromatosis type 1. <span class='html-italic'>Am. J. Med. Genet.</span> <b>1999</b>, <span class='html-italic'>89</span>, 1–6. [<a href="https://scholar.google.com/scholar_lookup?title=Epidemiology+of+neurofibromatosis+type+1&author=Friedman,+J.M.&publication_year=1999&journal=Am.+J.+Med.+Genet.&volume=89&pages=1%E2%80%936&doi=10.1002/(SICI)1096-8628(19990326)89:1%3C1::AID-AJMG3%3E3.0.CO;2-8" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19990326)89:1<1::AID-AJMG3>3.0.CO;2-8" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B6-genes-10-00633' class='html-x' data-content='6.'>Sabbagh, A.; Pasmant, E.; Imbard, A.; Luscan, A.; Soares, M.; Blanché, H.; Laurendeau, I.; Ferkal, S.; Vidaud, M.; Pinson, S.; et al. NF1 molecular characterization and neurofibromatosis type I genotype-phenotype correlation: The French experience. <span class='html-italic'>Hum. Mutat.</span> <b>2013</b>, <span class='html-italic'>34</span>, 1510–1518. [<a href="https://scholar.google.com/scholar_lookup?title=NF1+molecular+characterization+and+neurofibromatosis+type+I+genotype-phenotype+correlation:+The+French+experience&author=Sabbagh,+A.&author=Pasmant,+E.&author=Imbard,+A.&author=Luscan,+A.&author=Soares,+M.&author=Blanch%C3%A9,+H.&author=Laurendeau,+I.&author=Ferkal,+S.&author=Vidaud,+M.&author=Pinson,+S.&publication_year=2013&journal=Hum.+Mutat.&volume=34&pages=1510%E2%80%931518&doi=10.1002/humu.22392" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1002/humu.22392" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B7-genes-10-00633' class='html-x' data-content='7.'>Von Deimling, A.; Krone, W.; Menon, A.G. Neurofibromatosis type 1: Pathology, clinical features and molecular genetics. <span class='html-italic'>Brain Pathol.</span> <b>1995</b>, <span class='html-italic'>5</span>, 153–162. [<a href="https://scholar.google.com/scholar_lookup?title=Neurofibromatosis+type+1:+Pathology,+clinical+features+and+molecular+genetics&author=Von+Deimling,+A.&author=Krone,+W.&author=Menon,+A.G.&publication_year=1995&journal=Brain+Pathol.&volume=5&pages=153%E2%80%93162&doi=10.1111/j.1750-3639.1995.tb00589.x" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1111/j.1750-3639.1995.tb00589.x" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B8-genes-10-00633' class='html-x' data-content='8.'>Xu, G.; O’Connell, P.; Viskochil, D.; Cawthon, R.; Robertson, M.; Culver, M.; Dunn, D.; Stevens, J.; Gesteland, R.; White, R.; et al. The neurofibromatosis type 1 gene encodes a protein related to GAP. <span class='html-italic'>Cell</span> <b>1990</b>, <span class='html-italic'>62</span>, 599–608. [<a href="https://scholar.google.com/scholar_lookup?title=The+neurofibromatosis+type+1+gene+encodes+a+protein+related+to+GAP&author=Xu,+G.&author=O%E2%80%99Connell,+P.&author=Viskochil,+D.&author=Cawthon,+R.&author=Robertson,+M.&author=Culver,+M.&author=Dunn,+D.&author=Stevens,+J.&author=Gesteland,+R.&author=White,+R.&publication_year=1990&journal=Cell&volume=62&pages=599%E2%80%93608&doi=10.1016/0092-8674(90)90024-9" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/0092-8674(90)90024-9" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B9-genes-10-00633' class='html-x' data-content='9.'>Clementi, M.; Barbujani, G.; Turolla, L.; Tenconi, R. Neurofibromatosis-1: A maximum likelihood estimation of mutation rate. <span class='html-italic'>Hum. Genet.</span> <b>1990</b>, <span class='html-italic'>84</span>, 116–118. [<a href="https://scholar.google.com/scholar_lookup?title=Neurofibromatosis-1:+A+maximum+likelihood+estimation+of+mutation+rate&author=Clementi,+M.&author=Barbujani,+G.&author=Turolla,+L.&author=Tenconi,+R.&publication_year=1990&journal=Hum.+Genet.&volume=84&pages=116%E2%80%93118&doi=10.1007/BF00208923" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1007/BF00208923" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B10-genes-10-00633' class='html-xx' data-content='10.'>Kluwe, L.; Siebert, R.; Gesk, S.; Friedrich, R.E.; Tinschert, S.; Kehrer-Sawatzki, H.; Mautner, V.F. Screening 500 unselected neurofibromatosis 1 patients for deletions of the <span class='html-italic'>NF1</span> gene. <span class='html-italic'>Hum. Mutat.</span> <b>2004</b>, <span class='html-italic'>23</span>, 111–116. [<a href="https://scholar.google.com/scholar_lookup?title=Screening+500+unselected+neurofibromatosis+1+patients+for+deletions+of+the+NF1+gene&author=Kluwe,+L.&author=Siebert,+R.&author=Gesk,+S.&author=Friedrich,+R.E.&author=Tinschert,+S.&author=Kehrer-Sawatzki,+H.&author=Mautner,+V.F.&publication_year=2004&journal=Hum.+Mutat.&volume=23&pages=111%E2%80%93116&doi=10.1002/humu.10299" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1002/humu.10299" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B11-genes-10-00633' class='html-xx' data-content='11.'>Mautner, V.F.; Kluwe, L.; Friedrich, R.E.; Roehl, A.C.; Bammert, S.; Högel, J.; Spöri, H.; Cooper, D.N.; Kehrer-Sawatzki, H. Clinical characterisation of 29 neurofibromatosis type-1 patients with molecularly ascertained 1.4 Mb type-1 NF1 deletions. <span class='html-italic'>J. Med. Genet.</span> <b>2010</b>, <span class='html-italic'>47</span>, 623–630. [<a href="https://scholar.google.com/scholar_lookup?title=Clinical+characterisation+of+29+neurofibromatosis+type-1+patients+with+molecularly+ascertained+1.4+Mb+type-1+NF1+deletions&author=Mautner,+V.F.&author=Kluwe,+L.&author=Friedrich,+R.E.&author=Roehl,+A.C.&author=Bammert,+S.&author=H%C3%B6gel,+J.&author=Sp%C3%B6ri,+H.&author=Cooper,+D.N.&author=Kehrer-Sawatzki,+H.&publication_year=2010&journal=J.+Med.+Genet.&volume=47&pages=623%E2%80%93630&doi=10.1136/jmg.2009.075937" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1136/jmg.2009.075937" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="https://hal.archives-ouvertes.fr/hal-00557391/file/PEER_stage2_10.1136%2Fjmg.2009.075937.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B12-genes-10-00633' class='html-xx' data-content='12.'>Pasmant, E.; Sabbagh, A.; Spurlock, G.; Laurendeau, I.; Grillo, E.; Hamel, M.J.; Martin, L.; Barbarot, S.; Leheup, B.; Rodriguez, D.; et al. NF1 microdeletions in neurofibromatosis type 1: From genotype to phenotype. <span class='html-italic'>Hum. Mutat.</span> <b>2010</b>, <span class='html-italic'>31</span>, E1506–E1518. [<a href="https://scholar.google.com/scholar_lookup?title=NF1+microdeletions+in+neurofibromatosis+type+1:+From+genotype+to+phenotype&author=Pasmant,+E.&author=Sabbagh,+A.&author=Spurlock,+G.&author=Laurendeau,+I.&author=Grillo,+E.&author=Hamel,+M.J.&author=Martin,+L.&author=Barbarot,+S.&author=Leheup,+B.&author=Rodriguez,+D.&publication_year=2010&journal=Hum.+Mutat.&volume=31&pages=E1506%E2%80%93E1518&doi=10.1002/humu.21271" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1002/humu.21271" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B13-genes-10-00633' class='html-xx' data-content='13.'>Brems, H.; Chmara, M.; Sahbatou, M.; Denayer, E.; Taniguchi, K.; Kato, R.; Somers, R.; Messiaen, L.; De Schepper, S.; Fryns, J.P.; et al. Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. <span class='html-italic'>Nat. Genet.</span> <b>2007</b>, <span class='html-italic'>39</span>, 1120–1126. [<a href="https://scholar.google.com/scholar_lookup?title=Germline+loss-of-function+mutations+in+SPRED1+cause+a+neurofibromatosis+1-like+phenotype&author=Brems,+H.&author=Chmara,+M.&author=Sahbatou,+M.&author=Denayer,+E.&author=Taniguchi,+K.&author=Kato,+R.&author=Somers,+R.&author=Messiaen,+L.&author=De+Schepper,+S.&author=Fryns,+J.P.&publication_year=2007&journal=Nat.+Genet.&volume=39&pages=1120%E2%80%931126&doi=10.1038/ng2113" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1038/ng2113" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B14-genes-10-00633' class='html-xx' data-content='14.'>Pasmant, E.; Sabbagh, A.; Hanna, N.; Masliah-Planchon, J.; Jolly, E.; Goussard, P.; Ballerini, P.; Cartault, F.; Barbarot, S.; Landman-Parker, J.; et al. SPRED1 germline mutations caused a neurofibromatosis type 1 overlapping phenotype. <span class='html-italic'>J. Med. Genet.</span> <b>2009</b>, <span class='html-italic'>46</span>, 425–430. [<a href="https://scholar.google.com/scholar_lookup?title=SPRED1+germline+mutations+caused+a+neurofibromatosis+type+1+overlapping+phenotype&author=Pasmant,+E.&author=Sabbagh,+A.&author=Hanna,+N.&author=Masliah-Planchon,+J.&author=Jolly,+E.&author=Goussard,+P.&author=Ballerini,+P.&author=Cartault,+F.&author=Barbarot,+S.&author=Landman-Parker,+J.&publication_year=2009&journal=J.+Med.+Genet.&volume=46&pages=425%E2%80%93430&doi=10.1136/jmg.2008.065243" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1136/jmg.2008.065243" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="https://jmg.bmj.com/content/46/7/425.full.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B15-genes-10-00633' class='html-xx' data-content='15.'>Brems, H.; Pasmant, E.; Van Minkelen, R.; Wimmer, K.; Upadhyaya, M.; Legius, E.; Messiaen, L. Review and update of SPRED1 mutations causing Legius syndrome. <span class='html-italic'>Hum. Mutat.</span> <b>2012</b>, <span class='html-italic'>33</span>, 1538–1546. [<a href="https://scholar.google.com/scholar_lookup?title=Review+and+update+of+SPRED1+mutations+causing+Legius+syndrome&author=Brems,+H.&author=Pasmant,+E.&author=Van+Minkelen,+R.&author=Wimmer,+K.&author=Upadhyaya,+M.&author=Legius,+E.&author=Messiaen,+L.&publication_year=2012&journal=Hum.+Mutat.&volume=33&pages=1538%E2%80%931546&doi=10.1002/humu.22152" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1002/humu.22152" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B16-genes-10-00633' class='html-xx' data-content='16.'>Wakioka, T.; Sasaki, A.; Kato, R.; Shouda, T.; Matsumoto, A.; Miyoshi, K.; Tsuneoka, M.; Komiya, S.; Baron, R.; Yoshimura, A. Spred is a Sprouty-related suppressor of Ras signalling. <span class='html-italic'>Nature</span> <b>2001</b>, <span class='html-italic'>412</span>, 647–651. [<a href="https://scholar.google.com/scholar_lookup?title=Spred+is+a+Sprouty-related+suppressor+of+Ras+signalling&author=Wakioka,+T.&author=Sasaki,+A.&author=Kato,+R.&author=Shouda,+T.&author=Matsumoto,+A.&author=Miyoshi,+K.&author=Tsuneoka,+M.&author=Komiya,+S.&author=Baron,+R.&author=Yoshimura,+A.&publication_year=2001&journal=Nature&volume=412&pages=647%E2%80%93651&doi=10.1038/35088082" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1038/35088082" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B17-genes-10-00633' class='html-xx' data-content='17.'>Pasmant, E.; Parfait, B.; Luscan, A.; Goussard, P.; Briand-Suleau, A.; Laurendeau, I.; Fouveaut, C.; Leroy, C.; Montadert, A.; Wolkenstein, P.; et al. Neurofibromatosis type 1 molecular diagnosis: What can NGS do for you when you have a large gene with loss of function mutations? <span class='html-italic'>Eur. J. Hum. Genet.</span> <b>2015</b>, <span class='html-italic'>23</span>, 596–601. [<a href="https://scholar.google.com/scholar_lookup?title=Neurofibromatosis+type+1+molecular+diagnosis:+What+can+NGS+do+for+you+when+you+have+a+large+gene+with+loss+of+function+mutations?&author=Pasmant,+E.&author=Parfait,+B.&author=Luscan,+A.&author=Goussard,+P.&author=Briand-Suleau,+A.&author=Laurendeau,+I.&author=Fouveaut,+C.&author=Leroy,+C.&author=Montadert,+A.&author=Wolkenstein,+P.&publication_year=2015&journal=Eur.+J.+Hum.+Genet.&volume=23&pages=596%E2%80%93601&doi=10.1038/ejhg.2014.145" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1038/ejhg.2014.145" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B18-genes-10-00633' class='html-xx' data-content='18.'>Richards, S.; Aziz, N.; Bale, S.; Bick, D.; Das, S.; Gastier-Foster, J.; Grody, W.W.; Hegde, M.; Lyon, E.; Spector, E.; et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. <span class='html-italic'>Genet. Med.</span> <b>2015</b>, <span class='html-italic'>17</span>, 405–424. [<a href="https://scholar.google.com/scholar_lookup?title=Standards+and+guidelines+for+the+interpretation+of+sequence+variants:+A+joint+consensus+recommendation+of+the+American+College+of+Medical+Genetics+and+Genomics+and+the+Association+for+Molecular+Pathology&author=Richards,+S.&author=Aziz,+N.&author=Bale,+S.&author=Bick,+D.&author=Das,+S.&author=Gastier-Foster,+J.&author=Grody,+W.W.&author=Hegde,+M.&author=Lyon,+E.&author=Spector,+E.&publication_year=2015&journal=Genet.+Med.&volume=17&pages=405%E2%80%93424&doi=10.1038/gim.2015.30" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1038/gim.2015.30" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B19-genes-10-00633' class='html-xx' data-content='19.'>Ars, E.; Kruyer, H.; Morell, M.; Pros, E.; Serra, E.; Ravella, A.; Estivill, X.; Lázaro, C. Recurrent mutations in the <span class='html-italic'>NF1</span> gene are common among neurofibromatosis type 1 patients. <span class='html-italic'>J. Med. Genet.</span> <b>2003</b>, <span class='html-italic'>40</span>, e82. [<a href="https://scholar.google.com/scholar_lookup?title=Recurrent+mutations+in+the+NF1+gene+are+common+among+neurofibromatosis+type+1+patients&author=Ars,+E.&author=Kruyer,+H.&author=Morell,+M.&author=Pros,+E.&author=Serra,+E.&author=Ravella,+A.&author=Estivill,+X.&author=L%C3%A1zaro,+C.&publication_year=2003&journal=J.+Med.+Genet.&volume=40&pages=e82&doi=10.1136/jmg.40.6.e82" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1136/jmg.40.6.e82" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B20-genes-10-00633' class='html-xx' data-content='20.'>Side, L.; Taylor, B.; Cayouette, M.; Conner, E.; Thompson, P.; Luce, M.; Shannon, K. Homozygous inactivation of the <span class='html-italic'>NF1</span> gene in bone marrow cells from children with neurofibromatosis type 1 and malignant myeloid disorders. <span class='html-italic'>N. Engl. J. Med.</span> <b>1997</b>, <span class='html-italic'>336</span>, 1713–1720. [<a href="https://scholar.google.com/scholar_lookup?title=Homozygous+inactivation+of+the+NF1+gene+in+bone+marrow+cells+from+children+with+neurofibromatosis+type+1+and+malignant+myeloid+disorders&author=Side,+L.&author=Taylor,+B.&author=Cayouette,+M.&author=Conner,+E.&author=Thompson,+P.&author=Luce,+M.&author=Shannon,+K.&publication_year=1997&journal=N.+Engl.+J.+Med.&volume=336&pages=1713%E2%80%931720&doi=10.1056/NEJM199706123362404" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1056/NEJM199706123362404" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B21-genes-10-00633' class='html-xx' data-content='21.'>Pros, E.; Gómez, C.; Martín, T.; Fábregas, P.; Serra, E.; Lázaro, C. Nature and mRNA effect of 282 different NF1 point mutations: Focus on splicing alterations. <span class='html-italic'>Hum. Mutat.</span> <b>2008</b>, <span class='html-italic'>29</span>, E173–E193. [<a href="https://scholar.google.com/scholar_lookup?title=Nature+and+mRNA+effect+of+282+different+NF1+point+mutations:+Focus+on+splicing+alterations&author=Pros,+E.&author=G%C3%B3mez,+C.&author=Mart%C3%ADn,+T.&author=F%C3%A1bregas,+P.&author=Serra,+E.&author=L%C3%A1zaro,+C.&publication_year=2008&journal=Hum.+Mutat.&volume=29&pages=E173%E2%80%93E193&doi=10.1002/humu.20826" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1002/humu.20826" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B22-genes-10-00633' class='html-xx' data-content='22.'>Park, V.M.; Pivnick, E.K. Neurofibromatosis type 1 (NF1): A protein truncation assay yielding identification of mutations in 73% of patients. <span class='html-italic'>J. Med. Genet.</span> <b>1998</b>, <span class='html-italic'>35</span>, 813–820. [<a href="https://scholar.google.com/scholar_lookup?title=Neurofibromatosis+type+1+(NF1):+A+protein+truncation+assay+yielding+identification+of+mutations+in+73%25+of+patients&author=Park,+V.M.&author=Pivnick,+E.K.&publication_year=1998&journal=J.+Med.+Genet.&volume=35&pages=813%E2%80%93820&doi=10.1136/jmg.35.10.813" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1136/jmg.35.10.813" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B23-genes-10-00633' class='html-xx' data-content='23.'>Klose, A.; Peters, H.; Hoffmeyer, S.; Buske, A.; Lüder, A.; Hess, D.; Lehmann, R.; Nürnberg, P.; Tinschert, S. Two independent mutations in a family with neurofibromatosis type 1 (NF1). <span class='html-italic'>Am. J. Med. Genet.</span> <b>1999</b>, <span class='html-italic'>83</span>, 6–12. [<a href="https://scholar.google.com/scholar_lookup?title=Two+independent+mutations+in+a+family+with+neurofibromatosis+type+1+(NF1)&author=Klose,+A.&author=Peters,+H.&author=Hoffmeyer,+S.&author=Buske,+A.&author=L%C3%BCder,+A.&author=Hess,+D.&author=Lehmann,+R.&author=N%C3%BCrnberg,+P.&author=Tinschert,+S.&publication_year=1999&journal=Am.+J.+Med.+Genet.&volume=83&pages=6%E2%80%9312&doi=10.1002/(SICI)1096-8628(19990305)83:1%3C6::AID-AJMG3%3E3.0.CO;2-E" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19990305)83:1<6::AID-AJMG3>3.0.CO;2-E" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B24-genes-10-00633' class='html-xx' data-content='24.'>Upadhyaya, M.; Majounie, E.; Thompson, P.; Han, S.; Consoli, C.; Krawczak, M.; Cordeiro, I.; Cooper, D.N. Three different pathological lesions in the <span class='html-italic'>NF1</span> gene originating de novo in a family with neurofibromatosis type 1. <span class='html-italic'>Hum. Genet.</span> <b>2003</b>, <span class='html-italic'>112</span>, 12–17. [<a href="https://scholar.google.com/scholar_lookup?title=Three+different+pathological+lesions+in+the+NF1+gene+originating+de+novo+in+a+family+with+neurofibromatosis+type+1&author=Upadhyaya,+M.&author=Majounie,+E.&author=Thompson,+P.&author=Han,+S.&author=Consoli,+C.&author=Krawczak,+M.&author=Cordeiro,+I.&author=Cooper,+D.N.&publication_year=2003&journal=Hum.+Genet.&volume=112&pages=12%E2%80%9317&doi=10.1007/s00439-002-0840-1" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1007/s00439-002-0840-1" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B25-genes-10-00633' class='html-xx' data-content='25.'>Messiaen, L.; Yao, S.; Brems, H.; Callens, T.; Sathienkijkanchai, A.; Denayer, E.; Spencer, E.; Arn, P.; Babovic-Vuksanovic, D.; Bay, C.; et al. Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome. <span class='html-italic'>JAMA</span> <b>2009</b>, <span class='html-italic'>302</span>, 2111–2118. [<a href="https://scholar.google.com/scholar_lookup?title=Clinical+and+mutational+spectrum+of+neurofibromatosis+type+1-like+syndrome&author=Messiaen,+L.&author=Yao,+S.&author=Brems,+H.&author=Callens,+T.&author=Sathienkijkanchai,+A.&author=Denayer,+E.&author=Spencer,+E.&author=Arn,+P.&author=Babovic-Vuksanovic,+D.&author=Bay,+C.&publication_year=2009&journal=JAMA&volume=302&pages=2111%E2%80%932118&doi=10.1001/jama.2009.1663" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1001/jama.2009.1663" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B26-genes-10-00633' class='html-xx' data-content='26.'>Baralle, D.; Mattocks, C.; Kalidas, K.; Elmslie, F.; Whittaker, J.; Lees, M.; Ragge, N.; Patton, M.A.; Winter, R.M.; ffrench-Constant, C. Different mutations in the <span class='html-italic'>NF1</span> gene are associated with Neurofibromatosis-Noonan syndrome (NFNS). <span class='html-italic'>Am. J. Med. Genet. Part A</span> <b>2003</b>, <span class='html-italic'>119</span>, 1–8. [<a href="https://scholar.google.com/scholar_lookup?title=Different+mutations+in+the+NF1+gene+are+associated+with+Neurofibromatosis-Noonan+syndrome+(NFNS)&author=Baralle,+D.&author=Mattocks,+C.&author=Kalidas,+K.&author=Elmslie,+F.&author=Whittaker,+J.&author=Lees,+M.&author=Ragge,+N.&author=Patton,+M.A.&author=Winter,+R.M.&author=ffrench-Constant,+C.&publication_year=2003&journal=Am.+J.+Med.+Genet.+Part+A&volume=119&pages=1%E2%80%938&doi=10.1002/ajmg.a.20023" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1002/ajmg.a.20023" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B27-genes-10-00633' class='html-xx' data-content='27.'>De Luca, A.; Bottillo, I.; Sarkozy, A.; Carta, C.; Neri, C.; Bellacchio, E.; Schirinzi, A.; Conti, E.; Zampino, G.; Battaglia, A.; et al. <span class='html-italic'>NF1</span> gene mutations represent the major molecular event underlying neurofibromatosis-Noonan syndrome. <span class='html-italic'>Am. J. Hum. Genet.</span> <b>2005</b>, <span class='html-italic'>77</span>, 1092–1101. [<a href="https://scholar.google.com/scholar_lookup?title=NF1+gene+mutations+represent+the+major+molecular+event+underlying+neurofibromatosis-Noonan+syndrome&author=De+Luca,+A.&author=Bottillo,+I.&author=Sarkozy,+A.&author=Carta,+C.&author=Neri,+C.&author=Bellacchio,+E.&author=Schirinzi,+A.&author=Conti,+E.&author=Zampino,+G.&author=Battaglia,+A.&publication_year=2005&journal=Am.+J.+Hum.+Genet.&volume=77&pages=1092%E2%80%931101&doi=10.1086/498454" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1086/498454" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B28-genes-10-00633' class='html-xx' data-content='28.'>Stevenson, D.A.; Viskochil, D.H.; Rope, A.F.; Carey, J.C. Clinical and molecular aspects of an informative family with neurofibromatosis type 1 and Noonan phenotype. <span class='html-italic'>Clin. Genet.</span> <b>2006</b>, <span class='html-italic'>69</span>, 246–253. [<a href="https://scholar.google.com/scholar_lookup?title=Clinical+and+molecular+aspects+of+an+informative+family+with+neurofibromatosis+type+1+and+Noonan+phenotype&author=Stevenson,+D.A.&author=Viskochil,+D.H.&author=Rope,+A.F.&author=Carey,+J.C.&publication_year=2006&journal=Clin.+Genet.&volume=69&pages=246%E2%80%93253&doi=10.1111/j.1399-0004.2006.00576.x" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2006.00576.x" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://europepmc.org/articles/pmc3243644?pdf=render" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B29-genes-10-00633' class='html-xx' data-content='29.'>Hüffmeier, U.; Zenker, M.; Hoyer, J.; Fahsold, R.; Rauch, A. A variable combination of features of Noonan syndrome and neurofibromatosis type I are caused by mutations in the <span class='html-italic'>NF1</span> gene. <span class='html-italic'>Am. J. Med. Genet. Part A</span> <b>2006</b>, <span class='html-italic'>140</span>, 2749–2756. [<a href="https://scholar.google.com/scholar_lookup?title=A+variable+combination+of+features+of+Noonan+syndrome+and+neurofibromatosis+type+I+are+caused+by+mutations+in+the+NF1+gene&author=H%C3%BCffmeier,+U.&author=Zenker,+M.&author=Hoyer,+J.&author=Fahsold,+R.&author=Rauch,+A.&publication_year=2006&journal=Am.+J.+Med.+Genet.+Part+A&volume=140&pages=2749%E2%80%932756&doi=10.1002/ajmg.a.31547" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1002/ajmg.a.31547" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B30-genes-10-00633' class='html-xx' data-content='30.'>Nyström, A.M.; Ekvall, S.; Allanson, J.; Edeby, C.; Elinder, M.; Holmström, G.; Bondeson, M.L.; Annerén, G. Noonan syndrome and neurofibromatosis type I in a family with a novel mutation in NF1. <span class='html-italic'>Clin. Genet.</span> <b>2009</b>, <span class='html-italic'>76</span>, 524–534. [<a href="https://scholar.google.com/scholar_lookup?title=Noonan+syndrome+and+neurofibromatosis+type+I+in+a+family+with+a+novel+mutation+in+NF1&author=Nystr%C3%B6m,+A.M.&author=Ekvall,+S.&author=Allanson,+J.&author=Edeby,+C.&author=Elinder,+M.&author=Holmstr%C3%B6m,+G.&author=Bondeson,+M.L.&author=Anner%C3%A9n,+G.&publication_year=2009&journal=Clin.+Genet.&volume=76&pages=524%E2%80%93534&doi=10.1111/j.1399-0004.2009.01233.x" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2009.01233.x" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B31-genes-10-00633' class='html-xx' data-content='31.'>Ekvall, S.; Sjörs, K.; Jonzon, A.; Vihinen, M.; Annerén, G.; Bondeson, M.L. Novel association of neurofibromatosis type 1-causing mutations in families with neurofibromatosis-Noonan syndrome. <span class='html-italic'>Am. J. Med. Genet. Part A</span> <b>2014</b>, <span class='html-italic'>164</span>, 579–587. [<a href="https://scholar.google.com/scholar_lookup?title=Novel+association+of+neurofibromatosis+type+1-causing+mutations+in+families+with+neurofibromatosis-Noonan+syndrome&author=Ekvall,+S.&author=Sj%C3%B6rs,+K.&author=Jonzon,+A.&author=Vihinen,+M.&author=Anner%C3%A9n,+G.&author=Bondeson,+M.L.&publication_year=2014&journal=Am.+J.+Med.+Genet.+Part+A&volume=164&pages=579%E2%80%93587&doi=10.1002/ajmg.a.36313" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1002/ajmg.a.36313" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B32-genes-10-00633' class='html-xx' data-content='32.'>Bahuau, M.; Houdayer, C.; Assouline, B.; Blanchet-Bardon, C.; Le Merrer, M.; Lyonnet, S.; Giraud, S.; Récan, D.; Lakhdar, H.; Vidaud, M.; et al. Novel recurrent nonsense mutation causing neurofibromatosis type 1 (NF1) in a family segregating both NF1 and Noonan syndrome. <span class='html-italic'>Am. J. Med. Genet.</span> <b>1998</b>, <span class='html-italic'>75</span>, 265–272. [<a href="https://scholar.google.com/scholar_lookup?title=Novel+recurrent+nonsense+mutation+causing+neurofibromatosis+type+1+(NF1)+in+a+family+segregating+both+NF1+and+Noonan+syndrome&author=Bahuau,+M.&author=Houdayer,+C.&author=Assouline,+B.&author=Blanchet-Bardon,+C.&author=Le+Merrer,+M.&author=Lyonnet,+S.&author=Giraud,+S.&author=R%C3%A9can,+D.&author=Lakhdar,+H.&author=Vidaud,+M.&publication_year=1998&journal=Am.+J.+Med.+Genet.&volume=75&pages=265%E2%80%93272&doi=10.1002/(SICI)1096-8628(19980123)75:3%3C265::AID-AJMG8%3E3.0.CO;2-P" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19980123)75:3<265::AID-AJMG8>3.0.CO;2-P" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B33-genes-10-00633' class='html-xx' data-content='33.'>Pasmant, E.; Amiel, J.; Rodriguez, D.; Vidaud, M.; Vidaud, D.; Parfait, B. Two independent de novo mutations as a cause for neurofibromatosis type 1 and Noonan syndrome in a single family. <span class='html-italic'>Am. J. Med. Genet. Part A</span> <b>2012</b>, <span class='html-italic'>158</span>, 2290–2291. [<a href="https://scholar.google.com/scholar_lookup?title=Two+independent+de+novo+mutations+as+a+cause+for+neurofibromatosis+type+1+and+Noonan+syndrome+in+a+single+family&author=Pasmant,+E.&author=Amiel,+J.&author=Rodriguez,+D.&author=Vidaud,+M.&author=Vidaud,+D.&author=Parfait,+B.&publication_year=2012&journal=Am.+J.+Med.+Genet.+Part+A&volume=158&pages=2290%E2%80%932291&doi=10.1002/ajmg.a.35496" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1002/ajmg.a.35496" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B34-genes-10-00633' class='html-xx' data-content='34.'>Bertola, D.R.; Pereira, A.C.; Passetti, F.; de Oliveira, P.S.L.; Messiaen, L.; Gelb, B.D.; Kim, C.A.; Krieger, J.E. Neurofibromatosis-Noonan syndrome: Molecular evidence of the concurrence of both disorders in a patient. <span class='html-italic'>Am. J. Med. Genet. Part A</span> <b>2005</b>, <span class='html-italic'>136</span>, 242–245. [<a href="https://scholar.google.com/scholar_lookup?title=Neurofibromatosis-Noonan+syndrome:+Molecular+evidence+of+the+concurrence+of+both+disorders+in+a+patient&author=Bertola,+D.R.&author=Pereira,+A.C.&author=Passetti,+F.&author=de+Oliveira,+P.S.L.&author=Messiaen,+L.&author=Gelb,+B.D.&author=Kim,+C.A.&author=Krieger,+J.E.&publication_year=2005&journal=Am.+J.+Med.+Genet.+Part+A&volume=136&pages=242%E2%80%93245&doi=10.1002/ajmg.a.30813" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1002/ajmg.a.30813" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B35-genes-10-00633' class='html-xx' data-content='35.'>Thiel, C.; Wilken, M.; Zenker, M.; Sticht, H.; Fahsold, R.; Gusek-Schneider, G.-C.; Rauch, A. Independent NF1 and PTPN11 mutations in a family with neurofibromatosis-Noonan syndrome. <span class='html-italic'>Am. J. Med. Genet. Part A</span> <b>2009</b>, <span class='html-italic'>149</span>, 1263–1267. [<a href="https://scholar.google.com/scholar_lookup?title=Independent+NF1+and+PTPN11+mutations+in+a+family+with+neurofibromatosis-Noonan+syndrome&author=Thiel,+C.&author=Wilken,+M.&author=Zenker,+M.&author=Sticht,+H.&author=Fahsold,+R.&author=Gusek-Schneider,+G.-C.&author=Rauch,+A.&publication_year=2009&journal=Am.+J.+Med.+Genet.+Part+A&volume=149&pages=1263%E2%80%931267&doi=10.1002/ajmg.a.32837" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1002/ajmg.a.32837" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B36-genes-10-00633' class='html-xx' data-content='36.'>Prada, C.E.; Zarate, Y.A.; Hagenbuch, S.; Lovell, A.; Schorry, E.K.; Hopkin, R.J. Lethal presentation of neurofibromatosis and Noonan syndrome. <span class='html-italic'>Am. J. Med. Genet. Part A</span> <b>2011</b>, <span class='html-italic'>155</span>, 1360–1366. [<a href="https://scholar.google.com/scholar_lookup?title=Lethal+presentation+of+neurofibromatosis+and+Noonan+syndrome&author=Prada,+C.E.&author=Zarate,+Y.A.&author=Hagenbuch,+S.&author=Lovell,+A.&author=Schorry,+E.K.&author=Hopkin,+R.J.&publication_year=2011&journal=Am.+J.+Med.+Genet.+Part+A&volume=155&pages=1360%E2%80%931366&doi=10.1002/ajmg.a.33996" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1002/ajmg.a.33996" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B37-genes-10-00633' class='html-xx' data-content='37.'>Goriely, A. Decoding germline de novo point mutations. <span class='html-italic'>Nat. Genet.</span> <b>2016</b>, <span class='html-italic'>48</span>, 823–824. [<a href="https://scholar.google.com/scholar_lookup?title=Decoding+germline+de+novo+point+mutations&author=Goriely,+A.&publication_year=2016&journal=Nat.+Genet.&volume=48&pages=823%E2%80%93824&doi=10.1038/ng.3629" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1038/ng.3629" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B38-genes-10-00633' class='html-xx' data-content='38.'>Lázaro, C.; Gaona, A.; Ainsworth, P.; Tenconi, R.; Vidaud, D.; Kruyer, H.; Ars, E.; Volpini, V.; Estivill, X. Sex differences in mutational rate and mutational mechanism in the <span class='html-italic'>NF1</span> gene in neurofibromatosis type 1 patients. <span class='html-italic'>Hum. Genet.</span> <b>1996</b>, <span class='html-italic'>98</span>, 696–699. [<a href="https://scholar.google.com/scholar_lookup?title=Sex+differences+in+mutational+rate+and+mutational+mechanism+in+the+NF1+gene+in+neurofibromatosis+type+1+patients&author=L%C3%A1zaro,+C.&author=Gaona,+A.&author=Ainsworth,+P.&author=Tenconi,+R.&author=Vidaud,+D.&author=Kruyer,+H.&author=Ars,+E.&author=Volpini,+V.&author=Estivill,+X.&publication_year=1996&journal=Hum.+Genet.&volume=98&pages=696%E2%80%93699&doi=10.1007/s004390050287" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1007/s004390050287" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B39-genes-10-00633' class='html-xx' data-content='39.'>Goriely, A.; Wilkie, A.O.M. Paternal age effect mutations and selfish spermatogonial selection: Causes and consequences for human disease. <span class='html-italic'>Am. J. Hum. Genet.</span> <b>2012</b>, <span class='html-italic'>90</span>, 175–200. [<a href="https://scholar.google.com/scholar_lookup?title=Paternal+age+effect+mutations+and+selfish+spermatogonial+selection:+Causes+and+consequences+for+human+disease&author=Goriely,+A.&author=Wilkie,+A.O.M.&publication_year=2012&journal=Am.+J.+Hum.+Genet.&volume=90&pages=175%E2%80%93200&doi=10.1016/j.ajhg.2011.12.017" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1016/j.ajhg.2011.12.017" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B40-genes-10-00633' class='html-xx' data-content='40.'>Maher, G.J.; Ralph, H.K.; Ding, Z.; Koelling, N.; Mlcochova, H.; Giannoulatou, E.; Dhami, P.; Paul, D.S.; Stricker, S.H.; Beck, S.; et al. Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes. <span class='html-italic'>Genome Res.</span> <b>2018</b>, <span class='html-italic'>28</span>, 1779–1790. [<a href="https://scholar.google.com/scholar_lookup?title=Selfish+mutations+dysregulating+RAS-MAPK+signaling+are+pervasive+in+aged+human+testes&author=Maher,+G.J.&author=Ralph,+H.K.&author=Ding,+Z.&author=Koelling,+N.&author=Mlcochova,+H.&author=Giannoulatou,+E.&author=Dhami,+P.&author=Paul,+D.S.&author=Stricker,+S.H.&author=Beck,+S.&publication_year=2018&journal=Genome+Res.&volume=28&pages=1779%E2%80%931790&doi=10.1101/gr.239186.118" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1101/gr.239186.118" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>] [<a href="http://genome.cshlp.org/content/28/12/1779.full.pdf" target='_blank' rel="noopener noreferrer">Green Version</a>]</li><li id='B41-genes-10-00633' class='html-xx' data-content='41.'>Snajderova, M.; Riccardi, V.M.; Petrak, B.; Zemkova, D.; Zapletalova, J.; Mardesic, T.; Petrakova, A.; Lanska, V.; Marikova, T.; Bendova, S.; et al. The importance of advanced parental age in the origin of neurofibromatosis type 1. <span class='html-italic'>Am. J. Med. Genet. Part A</span> <b>2012</b>, <span class='html-italic'>158</span>, 519–523. [<a href="https://scholar.google.com/scholar_lookup?title=The+importance+of+advanced+parental+age+in+the+origin+of+neurofibromatosis+type+1&author=Snajderova,+M.&author=Riccardi,+V.M.&author=Petrak,+B.&author=Zemkova,+D.&author=Zapletalova,+J.&author=Mardesic,+T.&author=Petrakova,+A.&author=Lanska,+V.&author=Marikova,+T.&author=Bendova,+S.&publication_year=2012&journal=Am.+J.+Med.+Genet.+Part+A&volume=158&pages=519%E2%80%93523&doi=10.1002/ajmg.a.34413" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1002/ajmg.a.34413" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li><li id='B42-genes-10-00633' class='html-xx' data-content='42.'>Dubov, T.; Toledano-Alhadef, H.; Bokstein, F.; Constantini, S.; Ben-Shachar, S. The effect of parental age on the presence of de novo mutations—Lessons from neurofibromatosis type I. <span class='html-italic'>Mol. Genet. Genomic Med.</span> <b>2016</b>, <span class='html-italic'>4</span>, 480–486. [<a href="https://scholar.google.com/scholar_lookup?title=The+effect+of+parental+age+on+the+presence+of+de+novo+mutations%E2%80%94Lessons+from+neurofibromatosis+type+I&author=Dubov,+T.&author=Toledano-Alhadef,+H.&author=Bokstein,+F.&author=Constantini,+S.&author=Ben-Shachar,+S.&publication_year=2016&journal=Mol.+Genet.+Genomic+Med.&volume=4&pages=480%E2%80%93486&doi=10.1002/mgg3.222" class='google-scholar' target='_blank' rel='noopener noreferrer'>Google Scholar</a>] [<a href="https://doi.org/10.1002/mgg3.222" class='cross-ref' target='_blank' rel='noopener noreferrer'>CrossRef</a>]</li></ol></section><section id='FigureandTables' type='display-objects'><div class="html-fig-wrap" id="genes-10-00633-f001"> <div class='html-fig_img'> <div class="html-figpopup html-figpopup-link" data-counterslinkmanual = "https://www.mdpi.com/2073-4425/10/9/633/display" href="#fig_body_display_genes-10-00633-f001"> <img alt="Genes 10 00633 g001 550" data-large="/genes/genes-10-00633/article_deploy/html/images/genes-10-00633-g001.png" data-original="/genes/genes-10-00633/article_deploy/html/images/genes-10-00633-g001.png" data-lsrc="/genes/genes-10-00633/article_deploy/html/images/genes-10-00633-g001-550.jpg" /> <a class="html-expand html-figpopup" data-counterslinkmanual = "https://www.mdpi.com/2073-4425/10/9/633/display" href="#fig_body_display_genes-10-00633-f001"></a> </div> </div> <div class="html-fig_description"> <b>Figure 1.</b> Pedigrees of the six NF1 families. NF1 patients with molecular diagnosis, relatives reported as presenting a NF1 phenotype, and patients with a Legius syndrome are shown in black, black crosshatching, and gray, respectively. Haplotypes for the <span class='html-italic'>NF1</span> and <span class='html-italic'>SPRED1</span> loci are depicted for the corresponding patients. Arrows indicate the propositus in each family. Paternal and maternal ages at conception are indicated above the patient in blue and red, respectively, when available.  </div> </div> <div class="html-fig_show mfp-hide" id ="fig_body_display_genes-10-00633-f001" > <div class="html-caption" > <b>Figure 1.</b> Pedigrees of the six NF1 families. NF1 patients with molecular diagnosis, relatives reported as presenting a NF1 phenotype, and patients with a Legius syndrome are shown in black, black crosshatching, and gray, respectively. Haplotypes for the <span class='html-italic'>NF1</span> and <span class='html-italic'>SPRED1</span> loci are depicted for the corresponding patients. Arrows indicate the propositus in each family. Paternal and maternal ages at conception are indicated above the patient in blue and red, respectively, when available.</div> <div class="html-img"><img alt="Genes 10 00633 g001" data-large="/genes/genes-10-00633/article_deploy/html/images/genes-10-00633-g001.png" data-original="/genes/genes-10-00633/article_deploy/html/images/genes-10-00633-g001.png" data-lsrc="/genes/genes-10-00633/article_deploy/html/images/genes-10-00633-g001.png" /></div> </div><div class="html-table-wrap" id="genes-10-00633-t001"> <div class="html-table_wrap_td" > <div class="html-tablepopup html-tablepopup-link" data-counterslinkmanual = "https://www.mdpi.com/2073-4425/10/9/633/display" href='#table_body_display_genes-10-00633-t001'> <img alt="Table" data-lsrc="https://www.mdpi.com/img/table.png" /> <a class="html-expand html-tablepopup" data-counterslinkmanual = "https://www.mdpi.com/2073-4425/10/9/633/display" href="#table_body_display_genes-10-00633-t001"></a> </div> </div> <div class="html-table_wrap_discription"> <b>Table 1.</b> Clinical features of the patients with molecular diagnosis of NF1 in the six families. </div> </div> <div class="html-table_show mfp-hide " id ="table_body_display_genes-10-00633-t001" > <div class="html-caption" ><b>Table 1.</b> Clinical features of the patients with molecular diagnosis of NF1 in the six families.</div> <table > <thead ><tr ><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Family</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Patient</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Sex</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Age</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >CALS *</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Freckling</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Subcutaneous/Cutaneous NFs</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Plexiform NFs</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Lisch Nodules</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >OPG</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Skeletal Abnormalities</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Other</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' ><span class='html-italic'>NF1</span> Variant</th></tr></thead><tbody ><tr ><td rowspan='2' align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >1</td><td align='center' valign='middle' class='html-align-center' >IV-1</td><td align='center' valign='middle' class='html-align-center' >M</td><td align='center' valign='middle' class='html-align-center' >21</td><td align='center' valign='middle' class='html-align-center' >>6</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >Yes</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >Yes, bilateral</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >Mild scoliosis, <span class='html-italic'>cubitus valgus</span></td><td align='center' valign='middle' class='html-align-center' >Anemic nevus, learning disabilities, headaches, myopia</td><td align='center' valign='middle' class='html-align-center' >c.7084_7085insGA</td></tr><tr ><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >IV-3 <sup>#</sup></td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >F</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >18</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >>6</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes, Ax & In bilateral </td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >No</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes, bilateral</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >No</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Mild scoliosis</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Facial nevus, left hemiparesis, hyperopia, mild intellectual disability</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >c.1885G>A</td></tr><tr ><td rowspan='3' align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >2</td><td align='center' valign='middle' class='html-align-center' >II-1</td><td align='center' valign='middle' class='html-align-center' >M</td><td align='center' valign='middle' class='html-align-center' >41</td><td align='center' valign='middle' class='html-align-center' >>6</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >ND</td><td align='center' valign='middle' class='html-align-center' >None</td><td align='center' valign='middle' class='html-align-center' > </td><td align='center' valign='middle' class='html-align-center' >c.6642-5del</td></tr><tr ><td align='center' valign='middle' class='html-align-center' >III-2</td><td align='center' valign='middle' class='html-align-center' >F</td><td align='center' valign='middle' class='html-align-center' >14</td><td align='center' valign='middle' class='html-align-center' >>6</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >ND</td><td align='center' valign='middle' class='html-align-center' >None</td><td align='center' valign='middle' class='html-align-center' > </td><td align='center' valign='middle' class='html-align-center' >c.6642-5del</td></tr><tr ><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >III-3 <sup>#</sup></td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >M</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >2</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >>6</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes, Ax bilateral </td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes, bilateral</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Scoliosis</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Spinal NFs, xanthogranulomas, headaches, attention deficit disorder</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >c.4537C>T</td></tr><tr ><td rowspan='2' align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >3</td><td align='center' valign='middle' class='html-align-center' >III-1</td><td align='center' valign='middle' class='html-align-center' >F</td><td align='center' valign='middle' class='html-align-center' >20</td><td align='center' valign='middle' class='html-align-center' >>6</td><td align='center' valign='middle' class='html-align-center' >Yes, SM bilateral </td><td align='center' valign='middle' class='html-align-center' >Yes</td><td align='center' valign='middle' class='html-align-center' >Yes</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >Scoliosis</td><td align='center' valign='middle' class='html-align-center' > </td><td align='center' valign='middle' class='html-align-center' >c.5749+5G>A</td></tr><tr ><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >III-2 <sup>#</sup></td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >F</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >15</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >>6</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes, Ax bilateral</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >No</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >No</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >None</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' > </td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >c.2044C>T</td></tr><tr ><td rowspan='2' align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >4</td><td align='center' valign='middle' class='html-align-center' >III-2</td><td align='center' valign='middle' class='html-align-center' >F</td><td align='center' valign='middle' class='html-align-center' >26</td><td align='center' valign='middle' class='html-align-center' >>6</td><td align='center' valign='middle' class='html-align-center' >Yes, Ax bilateral </td><td align='center' valign='middle' class='html-align-center' >Yes</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >Yes, left</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >None</td><td align='center' valign='middle' class='html-align-center' >Short stature, low-set ears</td><td align='center' valign='middle' class='html-align-center' >c.5154dup</td></tr><tr ><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >III-5 <sup>#</sup></td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >M</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >39</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >>6</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes, Ax bilateral </td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >No</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes, bilateral</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >No</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >None</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Brugada syndrome <br>(paternal origin)</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >c.3314+2T>C</td></tr><tr ><td rowspan='2' align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >5</td><td align='center' valign='middle' class='html-align-center' >II-6 <sup>#</sup></td><td align='center' valign='middle' class='html-align-center' >F</td><td align='center' valign='middle' class='html-align-center' >23</td><td align='center' valign='middle' class='html-align-center' >>6</td><td align='center' valign='middle' class='html-align-center' >Yes, Ax</td><td align='center' valign='middle' class='html-align-center' >Yes</td><td align='center' valign='middle' class='html-align-center' >Yes</td><td align='center' valign='middle' class='html-align-center' >Yes, bilateral</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >Scoliosis, short stature</td><td align='center' valign='middle' class='html-align-center' >Breast cancer, headaches</td><td align='center' valign='middle' class='html-align-center' >c.3916C>T</td></tr><tr ><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >IV-1</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >M</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >18</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >>6</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >No</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Pseudarthrosis, sphenoid wing dysplasia</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Learning disabilities</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >c.2376del</td></tr><tr ><td rowspan='3' align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >6</td><td align='center' valign='middle' class='html-align-center' >I-2</td><td align='center' valign='middle' class='html-align-center' >F</td><td align='center' valign='middle' class='html-align-center' >45</td><td align='center' valign='middle' class='html-align-center' >>6</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >Yes</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >ND</td><td align='center' valign='middle' class='html-align-center' >ND</td><td align='center' valign='middle' class='html-align-center' >Scoliosis</td><td align='center' valign='middle' class='html-align-center' > </td><td align='center' valign='middle' class='html-align-center' >Complete deletion</td></tr><tr ><td align='center' valign='middle' class='html-align-center' >II-1</td><td align='center' valign='middle' class='html-align-center' >M</td><td align='center' valign='middle' class='html-align-center' >14</td><td align='center' valign='middle' class='html-align-center' >>6</td><td align='center' valign='middle' class='html-align-center' >Yes</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >No</td><td align='center' valign='middle' class='html-align-center' >None</td><td align='center' valign='middle' class='html-align-center' > </td><td align='center' valign='middle' class='html-align-center' > </td></tr><tr ><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >II-2 <sup>#</sup></td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >F</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >10</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >>6</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Yes</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >No</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >ND</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >ND</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >None</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Hypertelorism, congenital coronarocardiac fistula</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Complete deletion</td></tr></tbody> </table> <div class='html-table_foot html-p'><div class='html-p' style='text-indent:0em;'><span class='html-fn-content'>* CALS over 5 mm in greatest diameter in prepubertal individuals and over 15 mm in greatest diameter in postpubertal individuals. <sup>#</sup> Propositus. CALS: café-au-lait spots; NFs: neurofibromas; OPG: optic pathway glioma; Ax: axillary; In: inguinal; SM: sub-mammal; ND: not documented.</span></div><div style='clear:both;'></div></div> </div><div class="html-table-wrap" id="genes-10-00633-t002"> <div class="html-table_wrap_td" > <div class="html-tablepopup html-tablepopup-link" data-counterslinkmanual = "https://www.mdpi.com/2073-4425/10/9/633/display" href='#table_body_display_genes-10-00633-t002'> <img alt="Table" data-lsrc="https://www.mdpi.com/img/table.png" /> <a class="html-expand html-tablepopup" data-counterslinkmanual = "https://www.mdpi.com/2073-4425/10/9/633/display" href="#table_body_display_genes-10-00633-t002"></a> </div> </div> <div class="html-table_wrap_discription"> <b>Table 2.</b> Variants features and classification according to the ACMG-AMP guidelines. </div> </div> <div class="html-table_show mfp-hide " id ="table_body_display_genes-10-00633-t002" > <div class="html-caption" ><b>Table 2.</b> Variants features and classification according to the ACMG-AMP guidelines.</div> <table > <thead ><tr ><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Gene</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Variant</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Exon</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Protein</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Consequence</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Studied Sample </th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Techniques</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >ACMG-AMP classification</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Evidence of Pathogenicity</th><th align='center' valign='middle' style='border-top:solid thin;border-bottom:solid thin' class='html-align-center' >Reference</th></tr></thead><tbody ><tr ><td rowspan='10' align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' ><span class='html-italic'>NF1</span></td><td align='center' valign='middle' class='html-align-center' >c.7084_7085insGA</td><td align='center' valign='middle' class='html-align-center' >48</td><td align='center' valign='middle' class='html-align-center' >p.Asn2362Argfs*14</td><td align='center' valign='middle' class='html-align-center' >Frameshift</td><td align='center' valign='middle' class='html-align-center' >DNA + RNA</td><td align='center' valign='middle' class='html-align-center' >RT-PCR + Sanger</td><td align='center' valign='middle' class='html-align-center' >Pathogenic</td><td align='center' valign='middle' class='html-align-center' >PVS1+ PS2+PM2+PP4+PP5</td><td align='center' valign='middle' class='html-align-center' >Sabbagh et al., 2013 [<a href="#B6-genes-10-00633" class="html-bibr">6</a>]</td></tr><tr ><td align='center' valign='middle' class='html-align-center' >c.1885G>A</td><td align='center' valign='middle' class='html-align-center' >17</td><td align='center' valign='middle' class='html-align-center' >p.Gln616Glyfs*4</td><td align='center' valign='middle' class='html-align-center' >Creation of a new 3′ splice site</td><td align='center' valign='middle' class='html-align-center' >DNA + RNA</td><td align='center' valign='middle' class='html-align-center' >RT-PCR + Sanger</td><td align='center' valign='middle' class='html-align-center' >Pathogenic</td><td align='center' valign='middle' class='html-align-center' >PVS1+PS2+PP3+PP4+PP5</td><td align='center' valign='middle' class='html-align-center' >Ars et al., 2003 [<a href="#B19-genes-10-00633" class="html-bibr">19</a>]</td></tr><tr ><td align='center' valign='middle' class='html-align-center' >c.6642-5del</td><td align='center' valign='middle' class='html-align-center' >45</td><td align='center' valign='middle' class='html-align-center' >p.Phe2215Hisfs*6</td><td align='center' valign='middle' class='html-align-center' >Exon 45 skip</td><td align='center' valign='middle' class='html-align-center' >DNA + RNA</td><td align='center' valign='middle' class='html-align-center' >NGS + RT-PCR + Sanger</td><td align='center' valign='middle' class='html-align-center' >Pathogenic</td><td align='center' valign='middle' class='html-align-center' >PVS1+PM2+PP4</td><td align='center' valign='middle' class='html-align-center' >ND</td></tr><tr ><td align='center' valign='middle' class='html-align-center' >c.4537C>T</td><td align='center' valign='middle' class='html-align-center' >35</td><td align='center' valign='middle' class='html-align-center' >p.Arg1513*</td><td align='center' valign='middle' class='html-align-center' >Premature stop codon</td><td align='center' valign='middle' class='html-align-center' >DNA + RNA</td><td align='center' valign='middle' class='html-align-center' >NGS + RT-PCR + Sanger</td><td align='center' valign='middle' class='html-align-center' >Pathogenic</td><td align='center' valign='middle' class='html-align-center' >PVS1+PP4+PP5</td><td align='center' valign='middle' class='html-align-center' >Side et al., 1997 [<a href="#B20-genes-10-00633" class="html-bibr">20</a>]</td></tr><tr ><td align='center' valign='middle' class='html-align-center' >c.5749+5G>A</td><td align='center' valign='middle' class='html-align-center' >39</td><td align='center' valign='middle' class='html-align-center' >p.Ser1850fs*2</td><td align='center' valign='middle' class='html-align-center' >Exon 39 skip</td><td align='center' valign='middle' class='html-align-center' >DNA + RNA</td><td align='center' valign='middle' class='html-align-center' >NGS + RT-PCR + Sanger</td><td align='center' valign='middle' class='html-align-center' >Pathogenic</td><td align='center' valign='middle' class='html-align-center' >PVS1+PS2+PM2+PP3+PP4+PP5</td><td align='center' valign='middle' class='html-align-center' >Pros et al., 2008 [<a href="#B21-genes-10-00633" class="html-bibr">21</a>]</td></tr><tr ><td align='center' valign='middle' class='html-align-center' >c.2044C>T</td><td align='center' valign='middle' class='html-align-center' >18</td><td align='center' valign='middle' class='html-align-center' >p.(Gln682*)</td><td align='center' valign='middle' class='html-align-center' >Premature stop codon (predicted)</td><td align='center' valign='middle' class='html-align-center' >DNA</td><td align='center' valign='middle' class='html-align-center' >NGS + Sanger</td><td align='center' valign='middle' class='html-align-center' >Pathogenic</td><td align='center' valign='middle' class='html-align-center' >PVS1+PS2+PM2+PP4</td><td align='center' valign='middle' class='html-align-center' >ND</td></tr><tr ><td align='center' valign='middle' class='html-align-center' >c.5154dup</td><td align='center' valign='middle' class='html-align-center' >37</td><td align='center' valign='middle' class='html-align-center' >p.(Phe1719Ilefs*17)</td><td align='center' valign='middle' class='html-align-center' >Frameshift (predicted)</td><td align='center' valign='middle' class='html-align-center' >DNA</td><td align='center' valign='middle' class='html-align-center' >NGS + Sanger</td><td align='center' valign='middle' class='html-align-center' >Pathogenic</td><td align='center' valign='middle' class='html-align-center' >PVS1+PM2+PP4</td><td align='center' valign='middle' class='html-align-center' >ND</td></tr><tr ><td align='center' valign='middle' class='html-align-center' >c.3314+2T>C</td><td align='center' valign='middle' class='html-align-center' >25</td><td align='center' valign='middle' class='html-align-center' >p.?</td><td align='center' valign='middle' class='html-align-center' >Unknown</td><td align='center' valign='middle' class='html-align-center' >DNA</td><td align='center' valign='middle' class='html-align-center' >NGS + Sanger</td><td align='center' valign='middle' class='html-align-center' >Pathogenic</td><td align='center' valign='middle' class='html-align-center' >PVS1+PM2+PP4</td><td align='center' valign='middle' class='html-align-center' >ND</td></tr><tr ><td align='center' valign='middle' class='html-align-center' >c.3916C>T</td><td align='center' valign='middle' class='html-align-center' >29</td><td align='center' valign='middle' class='html-align-center' >p.Arg1306*</td><td align='center' valign='middle' class='html-align-center' >Premature stop codon</td><td align='center' valign='middle' class='html-align-center' >DNA + RNA</td><td align='center' valign='middle' class='html-align-center' >RT-PCR + Sanger</td><td align='center' valign='middle' class='html-align-center' >Pathogenic</td><td align='center' valign='middle' class='html-align-center' >PVS1+PS2+PP4+PP5</td><td align='center' valign='middle' class='html-align-center' >Park & Pivnick, 1998 [<a href="#B22-genes-10-00633" class="html-bibr">22</a>]</td></tr><tr ><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >c.2376del</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >20</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >p.Asn793Thrfs*28</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Frameshift</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >DNA + RNA</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >RT-PCR + Sanger</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Pathogenic</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >PVS1+PS2+PM2+PP4+PP5</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Sabbagh et al., 2013 [<a href="#B6-genes-10-00633" class="html-bibr">6</a>]</td></tr><tr ><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' ><span class='html-italic'>SPRED1</span></td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >c.944C>T</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >7</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >p.(Pro315Leu)</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Missense (predicted)</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >DNA</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >NGS + Sanger</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >Uncertain significance</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >PP3</td><td align='center' valign='middle' style='border-bottom:solid thin' class='html-align-center' >ND</td></tr></tbody> </table> <div class='html-table_foot html-p'><div class='html-p' style='text-indent:0em;'><span class='html-fn-content'>PVS1: null variant (nonsense, frameshift, canonical ±1 or two splice sites) in a gene where loss of function is a known mechanism of disease; PS2: de novo variant with both maternity and paternity confirmed; PM2: absent in the general population (controls) in gnomAD and dbSNP; PP3: multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact); PP4: patient’s phenotype is highly specific for NF1; PP5: reputable sources (LOVD, ClinVar) report variant as pathogenic. ND: not described. An asterisk (*) refers to a stop codon. A question mark (?) refers to unknown protein consequences.</span></div><div style='clear:both;'></div></div> </div></section> <section id="html-copyright"><br>© 2019 by the authors. Licensee MDPI, Basel, Switzerland. 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One NF1 Mutation may Conceal Another