208 lines
111 KiB
Text
208 lines
111 KiB
Text
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" class="no-js no-jr">
|
|
<head>
|
|
<!-- For pinger, set start time and add meta elements. -->
|
|
<script type="text/javascript">var ncbi_startTime = new Date();</script>
|
|
|
|
<!-- Logger begin -->
|
|
<meta name="ncbi_db" content="books">
|
|
<meta name="ncbi_pdid" content="book-part">
|
|
<meta name="ncbi_acc" content="NBK1306">
|
|
<meta name="ncbi_domain" content="gene">
|
|
<meta name="ncbi_report" content="reader">
|
|
<meta name="ncbi_type" content="fulltext">
|
|
<meta name="ncbi_objectid" content="">
|
|
<meta name="ncbi_pcid" content="/NBK1306/?report=reader">
|
|
<meta name="ncbi_pagename" content="SLC26A2-Related Multiple Epiphyseal Dysplasia - GeneReviews® - NCBI Bookshelf">
|
|
<meta name="ncbi_bookparttype" content="chapter">
|
|
<meta name="ncbi_app" content="bookshelf">
|
|
<!-- Logger end -->
|
|
|
|
<!--component id="Page" label="meta"/-->
|
|
<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>SLC26A2-Related Multiple Epiphyseal Dysplasia - GeneReviews® - NCBI Bookshelf</title>
|
|
<meta charset="utf-8">
|
|
<meta name="apple-mobile-web-app-capable" content="no">
|
|
<meta name="viewport" content="initial-scale=1,minimum-scale=1,maximum-scale=1,user-scalable=no">
|
|
<meta name="jr-col-layout" content="auto">
|
|
<meta name="jr-prev-unit" content="/books/n/gene/ao2/?report=reader">
|
|
<meta name="jr-next-unit" content="/books/n/gene/pendred/?report=reader">
|
|
<meta name="bk-toc-url" content="/books/n/gene/?report=toc">
|
|
<meta name="robots" content="INDEX,FOLLOW,NOARCHIVE">
|
|
<meta name="citation_inbook_title" content="GeneReviews® [Internet]">
|
|
<meta name="citation_title" content="SLC26A2-Related Multiple Epiphyseal Dysplasia">
|
|
<meta name="citation_publisher" content="University of Washington, Seattle">
|
|
<meta name="citation_date" content="2023/01/19">
|
|
<meta name="citation_author" content="Sheila Unger">
|
|
<meta name="citation_author" content="Andrea Superti-Furga">
|
|
<meta name="citation_pmid" content="20301483">
|
|
<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK1306/">
|
|
<meta name="citation_keywords" content="SLC26A2-Related Recessive MED (SLC26A2-rMED)">
|
|
<meta name="citation_keywords" content="SLC26A2-Related Recessive MED (SLC26A2-rMED)">
|
|
<meta name="citation_keywords" content="Sulfate transporter">
|
|
<meta name="citation_keywords" content="SLC26A2">
|
|
<meta name="citation_keywords" content="SLC26A2-Related Multiple Epiphyseal Dysplasia">
|
|
<link rel="schema.DC" href="http://purl.org/DC/elements/1.0/">
|
|
<meta name="DC.Title" content="SLC26A2-Related Multiple Epiphyseal Dysplasia">
|
|
<meta name="DC.Type" content="Text">
|
|
<meta name="DC.Publisher" content="University of Washington, Seattle">
|
|
<meta name="DC.Contributor" content="Sheila Unger">
|
|
<meta name="DC.Contributor" content="Andrea Superti-Furga">
|
|
<meta name="DC.Date" content="2023/01/19">
|
|
<meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK1306/">
|
|
<meta name="description" content="SLC26A2-related multiple epiphyseal dysplasia (SLC26A2-MED) is characterized by joint pain (usually in the hips or knees); malformations of hands, feet, and knees; and scoliosis. Approximately 50% of affected individuals have an abnormal finding at birth, including clubfoot, clinodactyly, or (rarely) cystic ear swelling. Onset of articular pain is variable but usually occurs in late childhood. Stature is usually within the normal range prior to puberty; in adulthood, stature is only slightly diminished and ranges from 150 to 180 cm. Functional disability is mild.">
|
|
<meta name="og:title" content="SLC26A2-Related Multiple Epiphyseal Dysplasia">
|
|
<meta name="og:type" content="book">
|
|
<meta name="og:description" content="SLC26A2-related multiple epiphyseal dysplasia (SLC26A2-MED) is characterized by joint pain (usually in the hips or knees); malformations of hands, feet, and knees; and scoliosis. Approximately 50% of affected individuals have an abnormal finding at birth, including clubfoot, clinodactyly, or (rarely) cystic ear swelling. Onset of articular pain is variable but usually occurs in late childhood. Stature is usually within the normal range prior to puberty; in adulthood, stature is only slightly diminished and ranges from 150 to 180 cm. Functional disability is mild.">
|
|
<meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK1306/">
|
|
<meta name="og:site_name" content="NCBI Bookshelf">
|
|
<meta name="og:image" content="https://www.ncbi.nlm.nih.gov/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-gene-lrg.png">
|
|
<meta name="twitter:card" content="summary">
|
|
<meta name="twitter:site" content="@ncbibooks">
|
|
<meta name="bk-non-canon-loc" content="/books/n/gene/edm/?report=reader">
|
|
<link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK1306/">
|
|
<link href="https://fonts.googleapis.com/css?family=Archivo+Narrow:400,700,400italic,700italic&subset=latin" rel="stylesheet" type="text/css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/libs.min.css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/jatsreader/ptpmc_3.22/css/jr.min.css">
|
|
<meta name="format-detection" content="telephone=no">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books.min.css" type="text/css">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css//books_print.min.css" type="text/css" media="print">
|
|
<link rel="stylesheet" href="/corehtml/pmc/css/bookshelf/2.26/css/books_reader.min.css" type="text/css">
|
|
<style type="text/css">p a.figpopup{display:inline !important} .bk_tt {font-family: monospace} .first-line-outdent .bk_ref {display: inline} .body-content h2, .body-content .h2 {border-bottom: 1px solid #97B0C8} .body-content h2.inline {border-bottom: none} a.page-toc-label , .jig-ncbismoothscroll a {text-decoration:none;border:0 !important} .temp-labeled-list .graphic {display:inline-block !important} .temp-labeled-list img{width:100%}</style>
|
|
|
|
<link rel="shortcut icon" href="//www.ncbi.nlm.nih.gov/favicon.ico">
|
|
<meta name="ncbi_phid" content="CE8DA9127C8A4361000000000033002A.m_5">
|
|
<meta name='referrer' content='origin-when-cross-origin'/><link type="text/css" rel="stylesheet" href="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/css/3852956/3849091.css"></head>
|
|
<body>
|
|
<!-- Book content! -->
|
|
|
|
|
|
<div id="jr" data-jr-path="/corehtml/pmc/jatsreader/ptpmc_3.22/"><div class="jr-unsupported"><table class="modal"><tr><td><span class="attn inline-block"></span><br />Your browser does not support the NLM PubReader view.<br />Go to <a href="/pmc/about/pr-browsers/">this page</a> to see a list of supported browsers<br />or return to the <br /><a href="/books/NBK1306/?report=classic">regular view</a>.</td></tr></table></div><div id="jr-ui" class="hidden"><nav id="jr-head"><div class="flexh tb"><div id="jr-tb1"><a id="jr-links-sw" class="hidden" title="Links"><svg xmlns="http://www.w3.org/2000/svg" version="1.1" x="0px" y="0px" viewBox="0 0 70.6 85.3" style="enable-background:new 0 0 70.6 85.3;vertical-align:middle" xml:space="preserve" width="24" height="24">
|
|
<style type="text/css">.st0{fill:#939598;}</style>
|
|
<g>
|
|
<path class="st0" d="M36,0C12.8,2.2-22.4,14.6,19.6,32.5C40.7,41.4-30.6,14,35.9,9.8"></path>
|
|
<path class="st0" d="M34.5,85.3c23.2-2.2,58.4-14.6,16.4-32.5c-21.1-8.9,50.2,18.5-16.3,22.7"></path>
|
|
<path class="st0" d="M34.7,37.1c66.5-4.2-4.8-31.6,16.3-22.7c42.1,17.9,6.9,30.3-16.4,32.5h1.7c-66.2,4.4,4.8,31.6-16.3,22.7 c-42.1-17.9-6.9-30.3,16.4-32.5"></path>
|
|
</g>
|
|
</svg> Books</a></div><div class="jr-rhead f1 flexh"><div class="head"><a href="/books/n/gene/ao2/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="body"><div class="t">SLC26A2-Related Multiple Epiphyseal Dysplasia</div><div class="j">GeneReviews® [Internet]</div></div><div class="tail"><a href="/books/n/gene/pendred/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></div><div id="jr-tb2"><a id="jr-bkhelp-sw" class="btn wsprkl hidden" title="Help with NLM PubReader">?</a><a id="jr-help-sw" class="btn wsprkl hidden" title="Settings and typography in NLM PubReader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512" preserveAspectRatio="none"><path d="M462,283.742v-55.485l-29.981-10.662c-11.431-4.065-20.628-12.794-25.274-24.001 c-0.002-0.004-0.004-0.009-0.006-0.013c-4.659-11.235-4.333-23.918,0.889-34.903l13.653-28.724l-39.234-39.234l-28.72,13.652 c-10.979,5.219-23.68,5.546-34.908,0.889c-0.005-0.002-0.01-0.003-0.014-0.005c-11.215-4.65-19.933-13.834-24-25.273L283.741,50 h-55.484l-10.662,29.981c-4.065,11.431-12.794,20.627-24.001,25.274c-0.005,0.002-0.009,0.004-0.014,0.005 c-11.235,4.66-23.919,4.333-34.905-0.889l-28.723-13.653l-39.234,39.234l13.653,28.721c5.219,10.979,5.545,23.681,0.889,34.91 c-0.002,0.004-0.004,0.009-0.006,0.013c-4.649,11.214-13.834,19.931-25.271,23.998L50,228.257v55.485l29.98,10.661 c11.431,4.065,20.627,12.794,25.274,24c0.002,0.005,0.003,0.01,0.005,0.014c4.66,11.236,4.334,23.921-0.888,34.906l-13.654,28.723 l39.234,39.234l28.721-13.652c10.979-5.219,23.681-5.546,34.909-0.889c0.005,0.002,0.01,0.004,0.014,0.006 c11.214,4.649,19.93,13.833,23.998,25.271L228.257,462h55.484l10.595-29.79c4.103-11.538,12.908-20.824,24.216-25.525 c0.005-0.002,0.009-0.004,0.014-0.006c11.127-4.628,23.694-4.311,34.578,0.863l28.902,13.738l39.234-39.234l-13.66-28.737 c-5.214-10.969-5.539-23.659-0.886-34.877c0.002-0.005,0.004-0.009,0.006-0.014c4.654-11.225,13.848-19.949,25.297-24.021 L462,283.742z M256,331.546c-41.724,0-75.548-33.823-75.548-75.546s33.824-75.547,75.548-75.547 c41.723,0,75.546,33.824,75.546,75.547S297.723,331.546,256,331.546z"></path></svg></a><a id="jr-fip-sw" class="btn wsprkl hidden" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-rtoc-sw" class="btn wsprkl hidden" title="Table of Contents"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,20h10v8H20V20zM36,20h44v8H36V20zM20,37.33h10v8H20V37.33zM36,37.33h44v8H36V37.33zM20,54.66h10v8H20V54.66zM36,54.66h44v8H36V54.66zM20,72h10v8 H20V72zM36,72h44v8H36V72z"></path></svg></a></div></div></nav><nav id="jr-dash" class="noselect"><nav id="jr-dash" class="noselect"><div id="jr-pi" class="hidden"><a id="jr-pi-prev" class="hidden" title="Previous page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a><div class="pginfo">Page <i class="jr-pg-pn">0</i> of <i class="jr-pg-lp">0</i></div><a id="jr-pi-next" class="hidden" title="Next page"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div><div id="jr-is-tb"><a id="jr-is-sw" class="btn wsprkl hidden" title="Switch between Figures/Tables strip and Progress bar"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><rect x="10" y="40" width="20" height="20"></rect><rect x="40" y="40" width="20" height="20"></rect><rect x="70" y="40" width="20" height="20"></rect></svg></a></div><nav id="jr-istrip" class="istrip hidden"><a id="jr-is-prev" href="#" class="hidden" title="Previous"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M80,40 60,65 80,90 70,90 50,65 70,40z M50,40 30,65 50,90 40,90 20,65 40,40z"></path><text x="35" y="25" textLength="60" style="font-size:25px">Prev</text></svg></a><a id="jr-is-next" href="#" class="hidden" title="Next"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M20,40 40,65 20,90 30,90 50,65 30,40z M50,40 70,65 50,90 60,90 80,65 60,40z"></path><text x="15" y="25" textLength="60" style="font-size:25px">Next</text></svg></a></nav><nav id="jr-progress"></nav></nav></nav><aside id="jr-links-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">NCBI Bookshelf</div></div><div class="cnt lol f1"><a href="/books/">Home</a><a href="/books/browse/">Browse All Titles</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://www.facebook.com/sharer/sharer.php?u=https://www.ncbi.nlm.nih.gov/books/NBK1306/"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24" preserveAspectRatio="none"><g><path d="M 17.996,32L 12,32 L 12,16 l-4,0 l0-5.514 l 4-0.002l-0.006-3.248C 11.993,2.737, 13.213,0, 18.512,0l 4.412,0 l0,5.515 l-2.757,0 c-2.063,0-2.163,0.77-2.163,2.209l-0.008,2.76l 4.959,0 l-0.585,5.514L 18,16L 17.996,32z"></path></g></svg> Share on Facebook</a><a class="btn share" target="_blank" rel="noopener noreferrer" href="https://twitter.com/intent/tweet?url=https://www.ncbi.nlm.nih.gov/books/NBK1306/&text=SLC26A2-Related%20Multiple%20Epiphyseal%20Dysplasia"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 33 33" style="vertical-align:middle" width="24" height="24"><g><path d="M 32,6.076c-1.177,0.522-2.443,0.875-3.771,1.034c 1.355-0.813, 2.396-2.099, 2.887-3.632 c-1.269,0.752-2.674,1.299-4.169,1.593c-1.198-1.276-2.904-2.073-4.792-2.073c-3.626,0-6.565,2.939-6.565,6.565 c0,0.515, 0.058,1.016, 0.17,1.496c-5.456-0.274-10.294-2.888-13.532-6.86c-0.565,0.97-0.889,2.097-0.889,3.301 c0,2.278, 1.159,4.287, 2.921,5.465c-1.076-0.034-2.088-0.329-2.974-0.821c-0.001,0.027-0.001,0.055-0.001,0.083 c0,3.181, 2.263,5.834, 5.266,6.438c-0.551,0.15-1.131,0.23-1.73,0.23c-0.423,0-0.834-0.041-1.235-0.118 c 0.836,2.608, 3.26,4.506, 6.133,4.559c-2.247,1.761-5.078,2.81-8.154,2.81c-0.53,0-1.052-0.031-1.566-0.092 c 2.905,1.863, 6.356,2.95, 10.064,2.95c 12.076,0, 18.679-10.004, 18.679-18.68c0-0.285-0.006-0.568-0.019-0.849 C 30.007,8.548, 31.12,7.392, 32,6.076z"></path></g></svg> Share on Twitter</a></div></aside><aside id="jr-rtoc-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Table of Content</div></div><div class="cnt lol f1"><a href="/books/n/gene/?report=reader">Title Information</a><a href="/books/n/gene/toc/?report=reader">Table of Contents Page</a></div></aside><aside id="jr-help-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Settings</div></div><div class="cnt f1"><div id="jr-typo-p" class="typo"><div><a class="sf btn wsprkl">A-</a><a class="lf btn wsprkl">A+</a></div><div><a class="bcol-auto btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 200 100" preserveAspectRatio="none"><text x="10" y="70" style="font-size:60px;font-family: Trebuchet MS, ArialMT, Arial, sans-serif" textLength="180">AUTO</text></svg></a><a class="bcol-1 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M15,25 85,25zM15,40 85,40zM15,55 85,55zM15,70 85,70z"></path></svg></a><a class="bcol-2 btn wsprkl"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M5,25 45,25z M55,25 95,25zM5,40 45,40z M55,40 95,40zM5,55 45,55z M55,55 95,55zM5,70 45,70z M55,70 95,70z"></path></svg></a></div></div><div class="lol"><a class="" href="/books/NBK1306/?report=classic">Switch to classic view</a><a href="/books/NBK1306/pdf/Bookshelf_NBK1306.pdf">PDF (504K)</a><a href="/books/NBK1306/?report=printable">Print View</a></div></div></aside><aside id="jr-bkhelp-p" class="hidden flexv"><div class="tb sk-htbar flexh"><div><a class="jr-p-close btn wsprkl">Done</a></div><div class="title-text f1">Help</div></div><div class="cnt f1 lol"><a id="jr-helpobj-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/help.xml" href="">Help</a><a href="mailto:info@ncbi.nlm.nih.gov?subject=PubReader%20feedback%20%2F%20NBK1306%20%2F%20sid%3ACE8B5AF87C7FFCB1_0191SID%20%2F%20phid%3ACE8DA9127C8A4361000000000033002A.4">Send us feedback</a><a id="jr-about-sw" data-path="/corehtml/pmc/jatsreader/ptpmc_3.22/" data-href="/corehtml/pmc/jatsreader/ptpmc_3.22/img/bookshelf/about.xml" href="">About PubReader</a></div></aside><aside id="jr-objectbox" class="thidden hidden"><div class="jr-objectbox-close wsprkl">✘</div><div class="jr-objectbox-inner cnt"><div class="jr-objectbox-drawer"></div></div></aside><nav id="jr-pm-left" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Previous Page</text></svg></nav><nav id="jr-pm-right" class="hidden"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 40 800" preserveAspectRatio="none"><text font-stretch="ultra-condensed" x="800" y="-15" text-anchor="end" transform="rotate(90)" font-size="18" letter-spacing=".1em">Next Page</text></svg></nav><nav id="jr-fip" class="hidden"><nav id="jr-fip-term-p"><input type="search" placeholder="search this page" id="jr-fip-term" autocorrect="off" autocomplete="off" /><a id="jr-fip-mg" class="wsprkl btn" title="Find"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 550 600" preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-fip-done" class="wsprkl btn" title="Dismiss find">✘</a></nav><nav id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK1306_"><span class="title" itemprop="name"><i>SLC26A2</i>-Related Multiple Epiphyseal Dysplasia</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: <i>SLC26A2</i>-Related Recessive MED (<i>SLC26A2</i>-rMED)</div><p class="contribs">Unger S, Superti-Furga A.</p><p class="fm-aai"><a href="#_NBK1306_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 19 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="edm.Summary" itemprop="description"><h2 id="_edm_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p><i>SLC26A2</i>-related multiple epiphyseal dysplasia (<i>SLC26A2</i>-MED) is characterized by joint pain (usually in the hips or knees); malformations of hands, feet, and knees; and scoliosis. Approximately 50% of affected individuals have an abnormal finding at birth, including clubfoot, clinodactyly, or (rarely) cystic ear swelling. Onset of articular pain is variable but usually occurs in late childhood. Stature is usually within the normal range prior to puberty; in adulthood, stature is only slightly diminished and ranges from 150 to 180 cm. Functional disability is mild.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>Diagnosis of <i>SLC26A2</i>-MED is based on detection of biallelic variants in <i>SLC26A2</i> by molecular genetic testing in an individual with compatible clinical and radiographic findings.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Physiotherapy for muscular strengthening and maintaining mobility; cautious use of analgesic medications such as nonsteroidal anti-inflammatory drugs; orthopedic surgery (joint replacement) as indicated; career counseling.</p><p><i>Prevention of secondary complications</i>: Intensive physiotherapy may help in delaying joint contractures and maintaining mobility.</p><p><i>Surveillance:</i> Radiographs as indicated.</p><p><i>Agents/circumstances to avoid:</i> Sports involving joint overload.</p></div><div><h4 class="inline">Genetic counseling.</h4><p><i>SLC26A2</i>-MED is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an <i>SLC26A2</i> pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the <i>SLC26A2</i> pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.</p></div></div><div id="edm.Diagnosis"><h2 id="_edm_Diagnosis_">Diagnosis</h2><div id="edm.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>SLC26A2</i>-related multiple epiphyseal dysplasia (<i>SLC26A2</i>-MED) <b>should be suspected</b> in individuals with the following clinical and radiographic features.</p><p>
|
|
<b>Clinical features</b>
|
|
</p><ul><li class="half_rhythm"><div>Joint pain (usually in the hips and knees). Onset of pain is variable, but usually occurs in late childhood. Some individuals have no pain.</div></li><li class="half_rhythm"><div>Deformity of hands, feet, and knees</div></li><li class="half_rhythm"><div>Scoliosis</div></li></ul><p>
|
|
<b>Radiographic features</b>
|
|
</p><ul><li class="half_rhythm"><div>Flat epiphyses with early arthritis (degenerative and painful changes in the articular cartilage of the hip joint)</div></li><li class="half_rhythm"><div>Mild brachydactyly</div></li><li class="half_rhythm"><div>Double-layered patella (i.e., presence of a separate anterior and posterior ossification layer) (see <a class="figpopup" href="/books/NBK1306/figure/edm.F1/?report=objectonly" target="object" rid-figpopup="figedmF1" rid-ob="figobedmF1">Figure 1</a>). Observed in approximately 60% of individuals on lateral knee radiographs, the presence of a double-layered patella is a quite specific, although not highly sensitive, sign of <i>SLC26A2</i>-MED [<a class="bibr" href="#edm.REF.m_kitie.2003.187" rid="edm.REF.m_kitie.2003.187">Mäkitie et al 2003</a>]. This finding appears to be age related and may disappear in adults.</div></li></ul><div class="iconblock whole_rhythm clearfix ten_col fig" id="figedmF1" co-legend-rid="figlgndedmF1"><a href="/books/NBK1306/figure/edm.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="figedmF1" rid-ob="figobedmF1"><img class="small-thumb" src="/books/NBK1306/bin/edm-Image001.gif" src-large="/books/NBK1306/bin/edm-Image001.jpg" alt="Figure 1. " /></a><div class="icnblk_cntnt" id="figlgndedmF1"><h4 id="edm.F1"><a href="/books/NBK1306/figure/edm.F1/?report=objectonly" target="object" rid-ob="figobedmF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">Double-layered patella Ballhausen et al [2003]; reprinted with permission from the BMJ Publishing Group</p></div></div><p><b>Family history</b> is consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.</p></div><div id="edm.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of <i>SLC26A2</i>-MED <b>is established</b> in a proband with the characteristic clinical and radiographic features described in <a href="#edm.Suggestive_Findings">Suggestive Findings</a> and biallelic pathogenic (or likely pathogenic) variants in <i>SLC26A2</i> identified by molecular genetic testing (see <a href="/books/NBK1306/table/edm.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobedmTmoleculargenetictestingusedin">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variants" and "likely pathogenic variants" are synonymous in a clinical setting, meaning that both are considered diagnostic, and both can be used for clinical decision making [<a class="bibr" href="#edm.REF.richards.2015.405" rid="edm.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. (2) Identification of biallelic <i>SLC26A2</i> variants of uncertain significance (or of one known <i>SLC26A2</i> pathogenic variant and one <i>SLC26A2</i> variant of uncertain significance) does not establish or rule out the diagnosis of the disorder.</p><p>Molecular genetic testing approaches can include a combination of <b>gene-targeted testing</b> (single-gene testing, multigene panel) and <b>comprehensive</b>
|
|
<b>genomic testing</b> (exome sequencing, genome sequencing) depending on the phenotype.</p><p>Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive findings described in <a href="#edm.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#edm.Option_1">Option 1</a>), whereas those with a phenotype indistinguishable from many other skeletal dysplasias are more likely to be diagnosed using genomic testing (see <a href="#edm.Option_2">Option 2</a>).</p><div id="edm.Option_1"><h4>Option 1</h4><p><b>Single-gene testing.</b> Sequence analysis of <i>SLC26A2</i> detects small intragenic deletions/insertions and missense, nonsense, and splice site variants. Typically, if only one or no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications; however, to date such variants have not been identified as a cause of this disorder.</p><p><b>A multigene panel</b> that includes <i>SLC26A2</i> and other genes of interest (see <a href="#edm.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</p><p>For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</p></div><div id="edm.Option_2"><h4>Option 2</h4><p>When the phenotype is indistinguishable from other skeletal dysplasias, <b>comprehensive</b>
|
|
<b>genomic testing</b>, which does not require the clinician to determine which gene is likely involved, is the best option. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible.</p><p>For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figedmTmoleculargenetictestingusedin"><a href="/books/NBK1306/table/edm.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobedmTmoleculargenetictestingusedin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="edm.T.molecular_genetic_testing_used_in"><a href="/books/NBK1306/table/edm.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobedmTmoleculargenetictestingusedin">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in <i>SLC26A2</i>-Related Multiple Epiphyseal Dysplasia </p></div></div></div></div></div><div id="edm.Clinical_Characteristics"><h2 id="_edm_Clinical_Characteristics_">Clinical Characteristics</h2><div id="edm.Clinical_Description"><h3>Clinical Description</h3><p><i>SLC26A2</i>-related multiple epiphyseal dysplasia (<i>SLC26A2</i>-MED) is characterized by early-onset joint pain, malformations of hands, feet, and knees, and scoliosis. Approximately 50% of affected individuals have an abnormal finding at birth, including clubfoot, clinodactyly, cleft palate, or (rarely) cystic ear swelling. However, only half of those with findings at birth are suspected of having a skeletal dysplasia.</p><p><b>Skeletal manifestations.</b> Chronic joint pain most often occurs in the hips, knees, wrists, and fingers. The onset of joint pain is variable; adolescents are usually symptomatic in multiple joints, and joint pain increases after physical exercise.</p><p>Waddling gait, hand/foot deformities (mild brachydactyly, clinodactyly, clubfoot, broadening of the space between the first and second toes), and mild scoliosis are also reported. Brachydactyly is evident after puberty in most individuals. Habitus is unremarkable in most affected individuals, except for genu valgum in some.</p><p><b>Stature</b> is usually within the normal range prior to puberty. In adulthood, stature is only slightly diminished, with the median height shifting from the 50th to the tenth centile; range of adult height is 150-180 cm. Approximately one third of affected adults have proportionately short stature that is two standard deviations below the mean for age.</p><p><b>Craniofacial features.</b> Facies are typically normal. Cleft palate may be present. Cystic ear swelling rarely occurs.</p><p><b>Progression.</b> Functional disability is mild or absent in childhood and adolescence [<a class="bibr" href="#edm.REF.ballhausen.2003.65" rid="edm.REF.ballhausen.2003.65">Ballhausen et al 2003</a>]; joint involvement progresses slightly in young adults, but hip and knee surgery is usually not needed. Bowing of the extremities is not observed.</p></div><div id="edm.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>Genotype-phenotype correlations indicate that the amount of residual activity of the sulfate transporter modulates the phenotype in this spectrum of disorders, which extends from lethal <a href="/books/n/gene/achon1b/?report=reader">achondrogenesis type 1B</a> (ACG1B) to mild <i>SLC26A2</i>-MED. Homozygosity or compound heterozygosity for pathogenic variants predicting stop codons or structural pathogenic variants in transmembrane domains of the sulfate transporter are associated with ACG1B, while pathogenic variants located in extracellular loops, in the cytoplasmic tail of the protein, or in the regulatory 5'-flanking region of the gene result in less severe phenotypes [<a class="bibr" href="#edm.REF.supertifurga.1996.144" rid="edm.REF.supertifurga.1996.144">Superti-Furga et al 1996</a>, <a class="bibr" href="#edm.REF.karniski.2001.1485" rid="edm.REF.karniski.2001.1485">Karniski 2001</a>, <a class="bibr" href="#edm.REF.maeda.2006.1143" rid="edm.REF.maeda.2006.1143">Maeda et al 2006</a>].</p><p>The pathogenic variant <a href="/books/NBK1306/table/edm.T.notable_slc26a2_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobedmTnotableslc26a2pathogenicvariant">p.Arg279Trp</a> is the most common <i>SLC26A2</i> variant found outside of Finland (45% of alleles); it results in the mild <i>SLC26A2</i>-MED phenotype when homozygous and mostly in <a href="/books/n/gene/diastrophic-d/?report=reader">diastrophic dysplasia</a> (DTD) and <a href="/books/n/gene/ao2/?report=reader">atelosteogenesis type 2</a> (AO2) phenotypes when found in the compound heterozygous state [<a class="bibr" href="#edm.REF.barbosa.2011.550" rid="edm.REF.barbosa.2011.550">Barbosa et al 2011</a>].</p><p>Pathogenic variant <a href="/books/NBK1306/table/edm.T.notable_slc26a2_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobedmTnotableslc26a2pathogenicvariant">p.Arg178Ter</a> is the second most common variant (9% of alleles) and is associated with a more severe DTD phenotype or even the perinatal-lethal AO2 phenotype, particularly when combined in <i>trans</i> with the <a href="/books/NBK1306/table/edm.T.notable_slc26a2_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobedmTnotableslc26a2pathogenicvariant">p.Arg279Trp</a> variant.</p><p>Pathogenic variants <a href="/books/NBK1306/table/edm.T.notable_slc26a2_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobedmTnotableslc26a2pathogenicvariant">p.Cys653Ser</a> and <a href="/books/NBK1306/table/edm.T.notable_slc26a2_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobedmTnotableslc26a2pathogenicvariant">c.-26+2T>C</a> are the third most common variants (8% of alleles).</p><p>Pathogenic variant <a href="/books/NBK1306/table/edm.T.notable_slc26a2_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobedmTnotableslc26a2pathogenicvariant">p.Cys653Ser</a> results in <i>SLC26A2</i>-MED when homozygous and in <i>SLC26A2</i>-MED or DTD when present in <i>trans</i> with other pathogenic variants [<a class="bibr" href="#edm.REF.czarnyratajczak.2010.3036" rid="edm.REF.czarnyratajczak.2010.3036">Czarny-Ratajczak et al 2010</a>].</p><p>Pathogenic variant <a href="/books/NBK1306/table/edm.T.notable_slc26a2_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobedmTnotableslc26a2pathogenicvariant">c.-26+2T>C</a> is sometimes referred to as the "Finnish" variant because it is much more frequent in Finland than in the remainder of the world population. It produces low levels of correctly spliced mRNA and results in DTD when homozygous. It is the only variant that has been identified in all four <i>SLC26A2</i>-related dysplasias, in compound heterozygosity with mild (<i>SLC26A2</i>-MED and DTD) or severe (AO2 and ACG1B) alleles [<a class="bibr" href="#edm.REF.dwyer.2010.3043" rid="edm.REF.dwyer.2010.3043">Dwyer et al 2010</a>].</p><p>The same pathogenic variants found in the ACG1B phenotype can also be found in the milder phenotypes (AO2 and DTD) if the second allele is a relatively mild variant. Indeed, missense variants located outside of the transmembrane domain of the sulfate transporter are often associated with residual activity that can "rescue" the effect of a null allele [<a class="bibr" href="#edm.REF.rossi.2001.159" rid="edm.REF.rossi.2001.159">Rossi & Superti-Furga 2001</a>].</p></div><div id="edm.Nomenclature"><h3>Nomenclature</h3><p>Multiple epiphyseal dysplasia (MED) is a disorder with clinical and genetic heterogeneity. In the past, the disorder was clinically subdivided into the milder Ribbing type, with flattened epiphysis and normal or near-normal stature; the more severe Fairbank type, with round, small epiphyses and short stature; and the unclassified types [<a class="bibr" href="#edm.REF.international_working_group_on_constitutional_diseases_of_bone.1998.376" rid="edm.REF.international_working_group_on_constitutional_diseases_of_bone.1998.376">International Working Group on Constitutional Diseases of Bone 1998</a>].</p><p>The genetic dissection of this heterogeneous group of conditions in recent years has provided a molecular-pathogenic classification of the different subtypes according to the gene involved:</p><ul><li class="half_rhythm"><div><i>SLC26A2-</i>related multiple epiphyseal dysplasia (<i>SLC26A2</i>-MED) is classified in the sulfation disorders group of the 2023 revised Nosology of Genetic Skeletal Disorders [<a class="bibr" href="#edm.REF.unger.2023" rid="edm.REF.unger.2023">Unger et al 2023</a>]. It accounts for approximately 25% of cases of MED.</div></li><li class="half_rhythm"><div><i>SLC26A2</i>-MED was originally referred to as recessive MED (rMED), and this term continues to be used regularly in the medical literature. However, in order to avoid confusion with the autosomal recessive <i>CANT1-</i>related phenotype that is also described as multiple epiphyseal dysplasia (MED) and to move toward dyadic naming, rMED caused by <i>SLC26A2</i> pathogenic variants is now designated "multiple epiphyseal dysplasia, <i>SLC26A2</i>-related" in the 2023 revised nosology [<a class="bibr" href="#edm.REF.unger.2023" rid="edm.REF.unger.2023">Unger et al 2023</a>].</div></li><li class="half_rhythm"><div>The other subtypes of MED are classified in the pseudoachondroplasia and the multiple epiphyseal dysplasias group in the 2023 revised nosology [<a class="bibr" href="#edm.REF.unger.2023" rid="edm.REF.unger.2023">Unger et al 2023</a>]. The most frequent form of MED is caused by autosomal dominant pathogenic variants in <i>COMP</i> (~50% of cases). The remaining 20%-25% of cases are split between <i>MATN3</i>, <i>COL9A1</i>, <i>COL9A2</i>, and <i>COL9A3</i>.</div></li><li class="half_rhythm"><div>Some individuals with MED do not have pathogenic variants in a known gene [<a class="bibr" href="#edm.REF.zankl.2007.150" rid="edm.REF.zankl.2007.150">Zankl et al 2007</a>, <a class="bibr" href="#edm.REF.unger.2008.19" rid="edm.REF.unger.2008.19">Unger et al 2008</a>]; in these individuals, MED remains unclassified.</div></li></ul></div><div id="edm.Prevalence"><h3>Prevalence</h3><p>Exact data about the prevalence of MED and its subtypes are not available. Based on the number of individuals seen in growth clinics, rheumatology clinics, and genetics clinics, and compared to conditions whose incidences are more precisely known (e.g., <a href="/books/n/gene/achondroplasia/?report=reader">achondroplasia</a>, <a href="/books/n/gene/oi/?report=reader">osteogenesis imperfecta</a>), it seems reasonable to estimate an overall prevalence of 1:20,000 [<a class="bibr" href="#edm.REF.unger.2008.19" rid="edm.REF.unger.2008.19">Unger et al 2008</a>]. This prevalence is probably an underestimation, as simplex cases (i.e., a single occurrence in a family) may remain undiagnosed. <i>SLC26A2</i>-MED is one of the most frequent forms of MED, accounting for almost 25% of all individuals diagnosed with MED [<a class="bibr" href="#edm.REF.jackson.2012.144" rid="edm.REF.jackson.2012.144">Jackson et al 2012</a>].</p></div></div><div id="edm.Genetically_Related_Allelic_Disorder"><h2 id="_edm_Genetically_Related_Allelic_Disorder_">Genetically Related (Allelic) Disorders</h2><p><i>SLC26A2</i>-related multiple epiphyseal dysplasia (<i>SLC26A2</i>-MED) is the mildest phenotype in the spectrum of <i>SLC26A2</i>-related autosomal recessive skeletal disorders (see <a href="/books/NBK1306/table/edm.T.slc26a2_skeletal_disorder_spectrum/?report=objectonly" target="object" rid-ob="figobedmTslc26a2skeletaldisorderspectrum">Table 2</a>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figedmTslc26a2skeletaldisorderspectrum"><a href="/books/NBK1306/table/edm.T.slc26a2_skeletal_disorder_spectrum/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobedmTslc26a2skeletaldisorderspectrum"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="edm.T.slc26a2_skeletal_disorder_spectrum"><a href="/books/NBK1306/table/edm.T.slc26a2_skeletal_disorder_spectrum/?report=objectonly" target="object" rid-ob="figobedmTslc26a2skeletaldisorderspectrum">Table 2. </a></h4><p class="float-caption no_bottom_margin"><i>SLC26A2</i> Skeletal Disorder Spectrum </p></div></div></div><div id="edm.Differential_Diagnosis"><h2 id="_edm_Differential_Diagnosis_">Differential Diagnosis</h2><p><i>SLC26A2</i>-related multiple epiphyseal dysplasia (<i>SLC26A2</i>-MED) needs to be distinguished from the more common autosomal dominant forms of multiple epiphyseal dysplasia (MED). Clinical and radiographic differences between the genetically distinct forms of these skeletal dysplasias may allow clinicians to distinguish between them (see <a href="/books/NBK1306/table/edm.T.autosomal_dominant_multiple_epiphy/?report=objectonly" target="object" rid-ob="figobedmTautosomaldominantmultipleepiphy">Table 3</a>).</p><p>Note: In contrast to autosomal dominant MED, prepubertal children with <i>SLC26A2</i>-MED usually do not have short stature.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figedmTautosomaldominantmultipleepiphy"><a href="/books/NBK1306/table/edm.T.autosomal_dominant_multiple_epiphy/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobedmTautosomaldominantmultipleepiphy"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="edm.T.autosomal_dominant_multiple_epiphy"><a href="/books/NBK1306/table/edm.T.autosomal_dominant_multiple_epiphy/?report=objectonly" target="object" rid-ob="figobedmTautosomaldominantmultipleepiphy">Table 3. </a></h4><p class="float-caption no_bottom_margin">Autosomal Dominant Multiple Epiphyseal Dysplasia * </p></div></div><p><b><i>CANT1</i>-related MED.</b> Homozygous <i>CANT1</i> missense variants were reported in four individuals from two families with radiographic phenotypes described as compatible with MED [<a class="bibr" href="#edm.REF.balasubramanian.2017.2415" rid="edm.REF.balasubramanian.2017.2415">Balasubramanian et al 2017</a>]. No further individuals have yet been described; thus, given the paucity of available data, no clear clinical and radiographic delineation can be made.</p><p><b>Unclassified</b>
|
|
<b>MED.</b> Some individuals with MED do not have pathogenic variants in a known gene [<a class="bibr" href="#edm.REF.zankl.2007.150" rid="edm.REF.zankl.2007.150">Zankl et al 2007</a>, <a class="bibr" href="#edm.REF.unger.2008.19" rid="edm.REF.unger.2008.19">Unger et al 2008</a>]; in these individuals, MED remains unclassified.</p></div><div id="edm.Management"><h2 id="_edm_Management_">Management</h2><div id="edm.Evaluations_Following_Initial_Diagno"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease in an individual diagnosed with <i>SLC26A2</i>-related multiple epiphyseal dysplasia (<i>SLC26A2</i>-MED), the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended:</p><ul><li class="half_rhythm"><div>Height measurement</div></li><li class="half_rhythm"><div>Elicitation of pain history</div></li><li class="half_rhythm"><div>Radiographs of the entire spine (AP and lateral), pelvis (AP), and knees (AP and lateral), to determine the extent and severity of joint involvement</div></li><li class="half_rhythm"><div>Consultation with a medical geneticist, certified genetic counselor, or certified advanced genetic nurse to inform affected individuals and their families about the nature, mode of inheritance, and implications of <i>SLC26A2</i>-MED to facilitate medical and personal decision making</div></li></ul></div><div id="edm.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Symptomatic individuals should be seen by a physical therapist and an orthopedist to assess the possibility of treatment (physiotherapy for muscular strengthening and maintaining mobility, cautious use of analgesic medications such as nonsteroidal anti-inflammatory drugs) and the optimal time for surgery (joint replacement), if indicated.</p><p>Intensive physiotherapy may delay joint contractures and help maintain mobility.</p><p>Psychosocial support addressing issues of chronic pain and career counseling is warranted.</p></div><div id="edm.Surveillance"><h3>Surveillance</h3><p>Radiographic surveillance by an orthopedist is appropriate.</p></div><div id="edm.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Sports involving joint overload are to be avoided.</p></div><div id="edm.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>Predictive testing of at-risk sibs is not indicated because no preventive measures or therapeutic interventions to reduce morbidity are available.</p><p>See <a href="#edm.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="edm.Pregnancy_Management"><h3>Pregnancy Management</h3><p>Women affected by <i>SLC26A2</i>-MED may suffer from chronic joint pain that may increase during pregnancy as a result of maternal weight gain. Appropriate pain management should be offered, and physical therapy should be intensified.</p><p>See <a href="https://www.mothertobaby.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MotherToBaby</a> for further information on medication use during pregnancy.</p></div><div id="edm.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="edm.Genetic_Counseling"><h2 id="_edm_Genetic_Counseling_">Genetic Counseling</h2><p>
|
|
<i>Genetic counseling is the process of providing individuals and families with
|
|
information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
|
|
make informed medical and personal decisions. The following section deals with genetic
|
|
risk assessment and the use of family history and genetic testing to clarify genetic
|
|
status for family members; it is not meant to address all personal, cultural, or
|
|
ethical issues that may arise or to substitute for consultation with a genetics
|
|
professional</i>. —ED.</p><div id="edm.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>SLC26A2</i>-related multiple epiphyseal dysplasia (<i>SLC26A2</i>-MED) is inherited in an autosomal recessive manner.</p></div><div id="edm.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
|
<b>Parents of a proband</b>
|
|
</p><ul><li class="half_rhythm"><div>The parents of an affected individual are presumed to be heterozygous for an <i>SLC26A2</i> pathogenic variant.</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of the proband to confirm that both parents are heterozygous for an <i>SLC26A2</i> pathogenic variant and to allow reliable recurrence risk assessment.</div></li><li class="half_rhythm"><div>If a pathogenic variant is detected in only one parent and parental identity testing has confirmed biological maternity and paternity, it is possible that one of the pathogenic variants identified in the proband occurred as a <i>de novo</i> event in the proband or as a postzygotic <i>de novo</i> event in a mosaic parent [<a class="bibr" href="#edm.REF.j_nsson.2017.519" rid="edm.REF.j_nsson.2017.519">Jónsson et al 2017</a>]. If the proband appears to have homozygous pathogenic variants (i.e., the same two pathogenic variants), additional possibilities to consider include:</div><ul><li class="half_rhythm"><div>A single- or multiexon deletion in the proband that was not detected by sequence analysis and that resulted in the artifactual appearance of homozygosity;</div></li><li class="half_rhythm"><div>Uniparental isodisomy for the parental chromosome with the pathogenic variant that resulted in homozygosity for the pathogenic variant in the proband.</div></li></ul></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and have normal stature. No evidence that carriers are at increased risk of developing degenerative joint disease has been presented.</div></li></ul><p>
|
|
<b>Sibs of a proband</b>
|
|
</p><ul><li class="half_rhythm"><div>If both parents are known to be heterozygous for an <i>SLC26A2</i> pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and have normal stature. No evidence that carriers are at increased risk of developing degenerative joint disease has been presented.</div></li></ul><p><b>Offspring of a proband.</b> Unless an affected individual's reproductive partner also has <i>SLC26A2</i>-MED or is a carrier, offspring will be obligate heterozygotes (carriers) for a pathogenic variant in <i>SLC26A2</i>.</p><p><b>Other family members.</b> Each sib of the proband's parents is at a 50% risk of being a carrier of an <i>SLC26A2</i> pathogenic variant.</p></div><div id="edm.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the <i>SLC26A2</i> pathogenic variants in the family.</p></div><div id="edm.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>
|
|
<b>Family planning</b>
|
|
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.</div></li><li class="half_rhythm"><div>Carrier testing for reproductive partners of known carriers should be considered.</div></li><li class="half_rhythm"><div>A <i>SLC26A2</i> founder variant has been identified in individuals of Finnish heritage (see <a href="/books/NBK1306/table/edm.T.notable_slc26a2_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobedmTnotableslc26a2pathogenicvariant">Table 4</a> and <a href="/books/n/gene/founder_finnish/?report=reader">Resources for Genetics Professionals — Genetic Disorders Associated with Founder Variants Common in the Finnish Population</a>).</div></li></ul></div><div id="edm.Prenatal_Testing_and_Preimplantation"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>SLC26A2</i> pathogenic variants have been identified in an affected family member, prenatal and preimplantation genetic testing are possible.</p><p>Differences in perspective may exist among medical professionals and in families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="edm.Resources"><h2 id="_edm_Resources_">Resources</h2><p>
|
|
<i>GeneReviews staff has selected the following disease-specific and/or umbrella
|
|
support organizations and/or registries for the benefit of individuals with this disorder
|
|
and their families. GeneReviews is not responsible for the information provided by other
|
|
organizations. For information on selection criteria, click <a href="/books/n/gene/app4/?report=reader">here</a>.</i></p>
|
|
<ul><li class="half_rhythm"><div>
|
|
<b>MedlinePlus</b>
|
|
</div><div>
|
|
<a href="https://medlineplus.gov/genetics/condition/multiple-epiphyseal-dysplasia/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Multiple epiphyseal dysplasia</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Human Growth Foundation</b>
|
|
</div><div>
|
|
<a href="https://www.hgfound.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">hgfound.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Little People of America</b>
|
|
</div><div><b>Phone:</b> 888-LPA-2001; 714-368-3689</div><div><b>Fax:</b> 707-721-1896</div><div><b>Email:</b> info@lpaonline.org</div><div>
|
|
<a href="https://www.lpaonline.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">lpaonline.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>MAGIC Foundation</b>
|
|
</div><div><b>Phone:</b> 630-836-8200</div><div><b>Email:</b> contactus@magicfoundation.org</div><div>
|
|
<a href="https://www.magicfoundation.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">magicfoundation.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>UCLA International Skeletal Dysplasia Registry (ISDR)</b>
|
|
</div><div><b>Phone:</b> 310-825-8998</div><div>
|
|
<a href="https://www.uclahealth.org/ortho/isdr" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">International Skeletal Dysplasia Registry</a>
|
|
</div></li></ul>
|
|
</div><div id="edm.Molecular_Genetics"><h2 id="_edm_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figedmmolgenTA"><a href="/books/NBK1306/table/edm.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobedmmolgenTA"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="edm.molgen.TA"><a href="/books/NBK1306/table/edm.molgen.TA/?report=objectonly" target="object" rid-ob="figobedmmolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">SLC26A2-Related Multiple Epiphyseal Dysplasia: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figedmmolgenTB"><a href="/books/NBK1306/table/edm.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobedmmolgenTB"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="edm.molgen.TB"><a href="/books/NBK1306/table/edm.molgen.TB/?report=objectonly" target="object" rid-ob="figobedmmolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for SLC26A2-Related Multiple Epiphyseal Dysplasia (View All in OMIM) </p></div></div><div id="edm.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>SLC26A2</i> pathogenic variants are responsible for the family of chondrodysplasias including <a href="/books/n/gene/achon1b/?report=reader">achondrogenesis type 1B</a> (ACG1B), <a href="/books/n/gene/ao2/?report=reader">atelosteogenesis type 2</a> (AO2), <a href="/books/n/gene/diastrophic-d/?report=reader">diastrophic dysplasia</a> (DTD), and <i>SLC26A2-</i>related multiple epiphyseal dysplasia (<i>SLC26A2</i>-MED). Impaired activity of the sulfate transporter in chondrocytes and fibroblasts results in the synthesis of proteoglycans that are not sulfated or are insufficiently sulfated [<a class="bibr" href="#edm.REF.rossi.1998.361" rid="edm.REF.rossi.1998.361">Rossi et al 1998</a>, <a class="bibr" href="#edm.REF.satoh.1998.12307" rid="edm.REF.satoh.1998.12307">Satoh et al 1998</a>], most likely because of intracellular sulfate depletion [<a class="bibr" href="#edm.REF.rossi.1996.18456" rid="edm.REF.rossi.1996.18456">Rossi et al 1996</a>, <a class="bibr" href="#edm.REF.gualeni.2010.453" rid="edm.REF.gualeni.2010.453">Gualeni et al 2010</a>]. Undersulfation of proteoglycans affects the composition of the extracellular matrix and leads to impairment of proteoglycan deposition, which is necessary for proper endochondral bone formation [<a class="bibr" href="#edm.REF.corsi.2001.1375" rid="edm.REF.corsi.2001.1375">Corsi et al 2001</a>, <a class="bibr" href="#edm.REF.forlino.2005.859" rid="edm.REF.forlino.2005.859">Forlino et al 2005</a>, <a class="bibr" href="#edm.REF.dawson.2011.653" rid="edm.REF.dawson.2011.653">Dawson 2011</a>]. The clinical severity can be correlated with the residual activities of the sulfate transporter resulting from different pathogenic variants [<a class="bibr" href="#edm.REF.rossi.1996.18456" rid="edm.REF.rossi.1996.18456">Rossi et al 1996</a>, <a class="bibr" href="#edm.REF.rossi.1997.741" rid="edm.REF.rossi.1997.741">Rossi et al 1997</a>, <a class="bibr" href="#edm.REF.corsi.2001.1375" rid="edm.REF.corsi.2001.1375">Corsi et al 2001</a>, <a class="bibr" href="#edm.REF.rossi.2001.159" rid="edm.REF.rossi.2001.159">Rossi & Superti-Furga 2001</a>, <a class="bibr" href="#edm.REF.rossi.2003.311" rid="edm.REF.rossi.2003.311">Rossi et al 2003</a>, <a class="bibr" href="#edm.REF.karniski.2004.2165" rid="edm.REF.karniski.2004.2165">Karniski 2004</a>, <a class="bibr" href="#edm.REF.maeda.2006.1143" rid="edm.REF.maeda.2006.1143">Maeda et al 2006</a>].</p><p>In a <i>Xenopus</i> oocyte model, the <a href="/books/NBK1306/table/edm.T.notable_slc26a2_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobedmTnotableslc26a2pathogenicvariant">p.Arg178Ter</a> pathogenic variant was shown to abolish sulfate transporter activity, and the <a href="/books/NBK1306/table/edm.T.notable_slc26a2_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobedmTnotableslc26a2pathogenicvariant">p.Val341del</a> pathogenic variant showed detectable but very low activity (17% of the wild type) of the sulfate transporter [<a class="bibr" href="#edm.REF.karniski.2001.1485" rid="edm.REF.karniski.2001.1485">Karniski 2001</a>]. The same variants associated in some individuals with the ACG1B phenotype can be found in individuals with a milder phenotype (AO2 and DTD) if the second allele is a relatively mild variant. Indeed, missense variants located outside the transmembrane domain of the sulfate transporter are often associated with residual activity that can "rescue" the effect of a null allele. Other conclusions from the <i>Xenopus</i> study are at odds with consistent clinical observations, the discrepancy probably being the result of temperature and cellular processing differences between <i>Xenopus</i> oocytes and humans (20 °C vs 37 °C) [<a class="bibr" href="#edm.REF.supertifurga.1996.144" rid="edm.REF.supertifurga.1996.144">Superti-Furga et al 1996</a>, <a class="bibr" href="#edm.REF.rossi.2001.159" rid="edm.REF.rossi.2001.159">Rossi & Superti-Furga 2001</a>, <a class="bibr" href="#edm.REF.supertifurga.2001" rid="edm.REF.supertifurga.2001">Superti-Furga 2001</a>, <a class="bibr" href="#edm.REF.supertifurga.2002" rid="edm.REF.supertifurga.2002">Superti-Furga 2002</a>]. Similar studies conducted in mammalian cells [<a class="bibr" href="#edm.REF.karniski.2004.2165" rid="edm.REF.karniski.2004.2165">Karniski 2004</a>] have produced results that are much more consistent with clinical genotype-phenotype correlations. These studies have essentially confirmed predictions that ACG1B-causing variants are associated with no residual transport activity, while the milder phenotypes result from either different combinations of "null" variants with other alleles that allow for some residual activity or from two variants with residual activity. Original observations were: (1) intracellular retention of the sulfate transporter protein with the variant <a href="/books/NBK1306/table/edm.T.notable_slc26a2_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobedmTnotableslc26a2pathogenicvariant">p.Gly678Val</a>; and (2) abnormal molecular weight of the sulfate transporter with <a href="/books/NBK1306/table/edm.T.notable_slc26a2_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobedmTnotableslc26a2pathogenicvariant">p.Gln454Pro</a>, possibly indicating protease sensitivity or aberrant glycosylation.</p><p><b>Mechanism of disease causation.</b> Loss of function</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figedmTnotableslc26a2pathogenicvariant"><a href="/books/NBK1306/table/edm.T.notable_slc26a2_pathogenic_variant/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobedmTnotableslc26a2pathogenicvariant"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="edm.T.notable_slc26a2_pathogenic_variant"><a href="/books/NBK1306/table/edm.T.notable_slc26a2_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobedmTnotableslc26a2pathogenicvariant">Table 4. </a></h4><p class="float-caption no_bottom_margin">Notable <i>SLC26A2</i> Pathogenic Variants </p></div></div></div></div><div id="edm.Chapter_Notes"><h2 id="_edm_Chapter_Notes_">Chapter Notes</h2><div id="edm.Author_History"><h3>Author History</h3><p>Diana Ballhausen, MD; Lausanne University Hospital (2002-2023)<br />Luisa Bonafé, MD, PhD; Lausanne University Hospital (2002-2023)<br />Lauréane Mittaz-Crettol, PhD; Lausanne University Hospital (2002-2023)<br />Andrea Superti-Furga, MD (2002-present)<br />Sheila Unger, MD (2023-present)</p></div><div id="edm.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>19 January 2023 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>23 January 2014 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>18 March 2010 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>27 December 2006 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>20 July 2004 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>29 August 2002 (me) Review posted live</div></li><li class="half_rhythm"><div>25 February 2002 (db) Original submission</div></li></ul></div></div><div id="edm.References"><h2 id="_edm_References_">References</h2><div id="edm.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.balasubramanian.2017.2415">Balasubramanian K, Li B, Krakow D, Nevarez L, Ho PJ, Ainsworth JA, Nickerson DA, Bamshad MJ, Immken L, Lachman RS, Cohn DH. MED resulting from recessively inherited mutations in the gene encoding calcium-activated nucleotidase CANT1. <span><span class="ref-journal">Am J Med Genet A. </span>2017;<span class="ref-vol">173</span>:2415–21.</span> [<a href="/pmc/articles/PMC5564418/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5564418</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28742282" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28742282</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.ballhausen.2003.65">Ballhausen D, Bonafé L, Terhal P, Unger SL, Bellus G, Classen M, Hamel BC, Spranger J, Zabel B, Cohn DH, Cole WG, Hecht JT, Superti-Furga A. Recessive multiple epiphyseal dysplasia (rMED): phenotype delineation in eighteen homozygotes for DTDST mutation R279W. <span><span class="ref-journal">J Med Genet. </span>2003;<span class="ref-vol">40</span>:65–71.</span> [<a href="/pmc/articles/PMC1735262/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1735262</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12525546" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12525546</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.barbosa.2011.550">Barbosa M, Sousa AB, Medeira A, Lourenço T, Saraiva J, Pinto-Basto J, Soares G, Fortuna AM, Superti-Furga A, Mittaz L, Reis-Lima M, Bonafé L. Clinical and molecular characterization of Diastrophic Dysplasia in the Portuguese population. <span><span class="ref-journal">Clin Genet. </span>2011;<span class="ref-vol">80</span>:550–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21155763" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21155763</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.corsi.2001.1375">Corsi A, Riminucci M, Fisher LW, Bianco P. Achondrogenesis type IB: agenesis of cartilage interterritorial matrix as the link between gene defect and pathological skeletal phenotype. <span><span class="ref-journal">Arch Pathol Lab Med. </span>2001;<span class="ref-vol">125</span>:1375–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11570921" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11570921</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.czarnyratajczak.2010.3036">Czarny-Ratajczak M, Bieganski T, Rogala P, Glowacki M, Trzeciak T, Kozlowski K. New intermediate phenotype between MED and DD caused by compound heterozygous mutations in the DTDST gene. <span><span class="ref-journal">Am J Med Genet A. </span>2010;<span class="ref-vol">152A</span>:3036–42.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21077204" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21077204</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.dawson.2011.653">Dawson PA. Sulfate in fetal development. <span><span class="ref-journal">Semin Cell Dev Biol. </span>2011;<span class="ref-vol">22</span>:653–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21419855" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21419855</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.dwyer.2010.3043">Dwyer E, Hyland J, Modaff P, Pauli RM. Genotype-phenotype correlation in DTDST dysplasias: Atelosteogenesis type II and diastrophic dysplasia variant in one family. <span><span class="ref-journal">Am J Med Genet A. </span>2010;<span class="ref-vol">152A</span>:3043–50.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21077202" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21077202</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.forlino.2005.859">Forlino A, Piazza R, Tiveron C, Della Torre S, Tatangelo L, Bonafé L, Gualeni B, Romano A, Pecora F, Superti-Furga A, Cetta G, Rossi A. A diastrophic dysplasia sulfate transporter (SLC26A2) mutant mouse: morphological and biochemical characterization of the resulting chondrodysplasia phenotype. <span><span class="ref-journal">Hum Mol Genet. </span>2005;<span class="ref-vol">14</span>:859–71.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15703192" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15703192</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.gualeni.2010.453">Gualeni B, Facchini M, De Leonardis F, Tenni R, Cetta G, Viola M, Passi A, Superti-Furga A, Forlino A, Rossi A. Defective proteoglycan sulfation of the growth plate zones causes reduced chondrocyte proliferation via an altered Indian hedgehog signalling. <span><span class="ref-journal">Matrix Biol. </span>2010;<span class="ref-vol">29</span>:453–60.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20470884" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20470884</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.international_working_group_on_constitutional_diseases_of_bone.1998.376">International Working Group on Constitutional Diseases of Bone. International nomenclature and classification of the osteochondrodysplasias, 1997. <span><span class="ref-journal">Am J Med Genet. </span>1998;<span class="ref-vol">79</span>:376–82.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9779805" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9779805</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.jackson.2012.144">Jackson GC, Mittaz-Crettol L, Taylor JA, Mortier GR, Spranger J, Zabel B, Le Merrer M, Cormier-Daire V, Hall CM, Offiah A, Wright MJ, Savarirayan R, Nishimura G, Ramsden SC, Elles R, Bonafé L, Superti-Furga A, Unger S, Zankl A, Briggs MD. Pseudoachondroplasia and multiple epiphyseal dysplasia: a 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution. <span><span class="ref-journal">Hum Mutat. </span>2012;<span class="ref-vol">33</span>:144–57.</span> [<a href="/pmc/articles/PMC3272220/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3272220</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21922596" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21922596</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.j_nsson.2017.519">Jónsson H, Sulem P, Kehr B, Kristmundsdottir S, Zink F, Hjartarson E, Hardarson MT, Hjorleifsson KE, Eggertsson HP, Gudjonsson SA, Ward LD, Arnadottir GA, Helgason EA, Helgason H, Gylfason A, Jonasdottir A, Jonasdottir A, Rafnar T, Frigge M, Stacey SN, Th Magnusson O, Thorsteinsdottir U, Masson G, Kong A, Halldorsson BV, Helgason A, Gudbjartsson DF, Stefansson K. Parental influence on human germline de novo mutations in 1,548 trios from Iceland. <span><span class="ref-journal">Nature. </span>2017;<span class="ref-vol">549</span>:519–22.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28959963" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28959963</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.karniski.2004.2165">Karniski LP. Functional expression and cellular distribution of diastrophic dysplasia sulfate transporter (DTDST) gene mutations in HEK cells. <span><span class="ref-journal">Hum Mol Genet. </span>2004;<span class="ref-vol">13</span>:2165–71.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15294877" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15294877</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.karniski.2001.1485">Karniski LP. Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene: correlation between sulfate transport activity and chondrodysplasia phenotype. <span><span class="ref-journal">Hum Mol Genet. </span>2001;<span class="ref-vol">10</span>:1485–90.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11448940" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11448940</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.maeda.2006.1143">Maeda K, Miyamoto Y, Sawai H, Karniski LP, Nakashima E, Nishimura G, Ikegawa S. A compound heterozygote harboring novel and recurrent DTDST mutations with intermediate phenotype between atelosteogenesis type II and diastrophic dysplasia. <span><span class="ref-journal">Am J Med Genet A. </span>2006;<span class="ref-vol">140</span>:1143–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16642506" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16642506</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.m_kitie.2003.187">Mäkitie O, Savarirayan R, Bonafé L, Robertson S, Susic M, Superti-Furga A, Cole WG. Autosomal recessive multiple epiphyseal dysplasia with homozygosity for C653S in the DTDST gene: double-layer patella as a reliable sign. <span><span class="ref-journal">Am J Med Genet. </span>2003;<span class="ref-vol">122A</span>:187–92.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12966518" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12966518</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.richards.2015.405">Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, 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><span class="ref-journal">Genet Med. </span>2015;<span class="ref-vol">17</span>:405–24.</span> [<a href="/pmc/articles/PMC4544753/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4544753</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25741868" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25741868</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.rossi.1996.18456">Rossi A, Bonaventure J, Delezoide AL, Cetta G, Superti-Furga A. Undersulfation of proteoglycans synthesized by chondrocytes from a patient with achondrogenesis type 1B homozygous for an L483P substitution in the diastrophic dysplasia sulfate transporter. <span><span class="ref-journal">J Biol Chem. </span>1996;<span class="ref-vol">271</span>:18456–64.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8702490" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8702490</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.rossi.1997.741">Rossi A, Bonaventure J, Delezoide AL, Superti-Furga A, Cetta G. Undersulfation of cartilage proteoglycans ex vivo and increased contribution of amino acid sulfur to sulfation in vitro in McAlister dysplasia/atelosteogenesis type 2. <span><span class="ref-journal">Eur J Biochem. </span>1997;<span class="ref-vol">248</span>:741–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9342225" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9342225</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.rossi.2003.311">Rossi A, Cetta G, Piazza R, Bonaventure J, Steinmann B, Supereti-Furga A. In vitro proteoglycan sulfation derived from sulfhydryl compounds in sulfate transporter chondrodysplasias. <span><span class="ref-journal">Pediatr Pathol Mol Med. </span>2003;<span class="ref-vol">22</span>:311–21.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14692227" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14692227</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.rossi.1998.361">Rossi A, Kaitila I, Wilcox WR, Rimoin DL, Steinmann B, Cetta G, Superti-Furga A. Proteoglycan sulfation in cartilage and cell cultures from patients with sulfate transporter chondrodysplasias: relationship to clinical severity and indications on the role of intracellular sulfate production. <span><span class="ref-journal">Matrix Biol. </span>1998;<span class="ref-vol">17</span>:361–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9822202" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9822202</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.rossi.2001.159">Rossi A, Superti-Furga A. Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene (SLC26A2): 22 novel mutations, mutation review, associated skeletal phenotypes, and diagnostic relevance. <span><span class="ref-journal">Hum Mutat. </span>2001;<span class="ref-vol">17</span>:159–71.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11241838" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11241838</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.satoh.1998.12307">Satoh H, Susaki M, Shukunami C, Iyama K, Negoro T, Hiraki Y. Functional analysis of diastrophic dysplasia sulfate transporter. Its involvement in growth regulation of chondrocytes mediated by sulfated proteoglycans. <span><span class="ref-journal">J Biol Chem. </span>1998;<span class="ref-vol">273</span>:12307–15.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9575183" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9575183</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.stenson.2020.1197">Stenson PD, Mort M, Ball EV, Chapman M, Evans K, Azevedo L, Hayden M, Heywood S, Millar DS, Phillips AD, Cooper DN. The Human Gene Mutation Database (HGMD®): optimizing its use in a clinical diagnostic or research setting. <span><span class="ref-journal">Hum Genet. </span>2020;<span class="ref-vol">139</span>:1197–207.</span> [<a href="/pmc/articles/PMC7497289/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7497289</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32596782" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32596782</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.supertifurga.2001">Superti-Furga A. Defects in sulfate metabolism and skeletal dysplasias. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Vogelstein B, Childs B, eds. <em>The Metabolic and Molecular Bases of Inherited Disease.</em> 8 ed. New York, NY: McGraw-Hill; 2001:5189-201.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.supertifurga.2002">Superti-Furga A. Skeletal dysplasias related to defects in sulfate metabolism. In: Royce P, Steinmann B, eds. <em>Connective Tissue and Its Heritable Disorders.</em> 2 ed. New York, NY: Wiley-Liss, Inc; 2002:939-60.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.supertifurga.1996.144">Superti-Furga A, Rossi A, Steinmann B, Gitzelmann R. A chondrodysplasia family produced by mutations in the diastrophic dysplasia sulfate transporter gene: genotype/phenotype correlations. <span><span class="ref-journal">Am J Med Genet. </span>1996;<span class="ref-vol">63</span>:144–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8723100" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8723100</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.unger.2008.19">Unger S, Bonafé L, Superti-Furga A. Multiple epiphyseal dysplasia: clinical and radiographic features, differential diagnosis and molecular basis. <span><span class="ref-journal">Best Pract Res Clin Rheumatol. </span>2008;<span class="ref-vol">22</span>:19–32.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18328978" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18328978</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.unger.2023">Unger S, Ferreira CR, Mortier GR, Ali H, Bertola DR, Calder A, Cohn DH, Cormier-Daire V, Girisha KM, Hall C, Krakow D, Makitie O, Mundlos S, Nishimura G, Robertson SP, Savarirayan R, Sillence D, Simon M, Sutton VR, Warman ML, Superti-Furga A. Nosology of genetic skeletal disorders: 2023 revision. <span><span class="ref-journal">Am J Med Genet A. </span>2023.</span> Epub ahead of print. [<a href="/pmc/articles/PMC10081954/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC10081954</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36779427" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36779427</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="edm.REF.zankl.2007.150">Zankl A, Jackson GC, Crettol LM, Taylor J, Elles R, Mortier GR, Spranger J, Zabel B, Unger S, Merrer ML, Cormier-Daire V, Hall CM, Wright MJ, Bonafé L, Superti-Furga A, Briggs MD. Preselection of cases through expert clinical and radiographic review significantly increases mutation detection rate in multiple epiphyseal dysplasia. <span><span class="ref-journal">Eur J Hum Genet. </span>2007;<span class="ref-vol">15</span>:150–4.</span> [<a href="/pmc/articles/PMC2670452/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2670452</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/17133256" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17133256</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK1306_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Sheila Unger</span>, MD<div class="affiliation small">Associate Professor of Genetics<br />University of Lausanne;<br />Lausanne University Hospital<br />Lausanne, Switzerland<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="hc.vuhc@regnu.aliehs" class="oemail">hc.vuhc@regnu.aliehs</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Andrea Superti-Furga</span>, MD<div class="affiliation small">Professor of Pediatrics and Genetics<br />University of Lausanne;<br />Lausanne University Hospital<br />Lausanne, Switzerland<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="hc.linu@itrepusa" class="oemail">hc.linu@itrepusa</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">August 29, 2002</span>; Last Update: <span itemprop="dateModified">January 19, 2023</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. GeneReviews is
|
|
a registered trademark of the University of Washington, Seattle. All rights
|
|
reserved.<p class="small">GeneReviews® chapters are owned by the University of Washington. Permission is
|
|
hereby granted to reproduce, distribute, and translate copies of content materials for
|
|
noncommercial research purposes only, provided that (i) credit for source (<a href="http://www.genereviews.org/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">http://www.genereviews.org/</a>) and copyright (© 1993-2025 University of
|
|
Washington) are included with each copy; (ii) a link to the original material is provided
|
|
whenever the material is published elsewhere on the Web; and (iii) reproducers,
|
|
distributors, and/or translators comply with the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
|
|
Disclaimer</a>. No further modifications are allowed. For clarity, excerpts
|
|
of GeneReviews chapters for use in lab reports and clinic notes are a permitted
|
|
use.</p><p class="small">For more information, see the <a href="https://www.ncbi.nlm.nih.gov/books/n/gene/GRcopyright_permiss/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">GeneReviews® Copyright Notice and Usage
|
|
Disclaimer</a>.</p><p class="small">For questions regarding permissions or whether a specified use is allowed,
|
|
contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Unger S, Superti-Furga A. SLC26A2-Related Multiple Epiphyseal Dysplasia. 2002 Aug 29 [Updated 2023 Jan 19]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gene/ao2/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/pendred/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobedmTmoleculargenetictestingusedin"><div id="edm.T.molecular_genetic_testing_used_in" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>SLC26A2</i>-Related Multiple Epiphyseal Dysplasia</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1306/table/edm.T.molecular_genetic_testing_used_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__edm.T.molecular_genetic_testing_used_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_edm.T.molecular_genetic_testing_used_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_edm.T.molecular_genetic_testing_used_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_edm.T.molecular_genetic_testing_used_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_edm.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>SLC26A2</i>
|
|
</td><td headers="hd_h_edm.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_edm.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100% <sup>4, 5</sup></td></tr><tr><td headers="hd_h_edm.T.molecular_genetic_testing_used_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>6</sup></td><td headers="hd_h_edm.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None reported <sup>7</sup></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="edm.TF.1.1"><p class="no_margin">See <a href="/books/NBK1306/?report=reader#edm.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="edm.TF.1.2"><p class="no_margin">See <a href="#edm.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="edm.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="edm.TF.1.4"><p class="no_margin">The four most common <i>SLC26A2</i> pathogenic variants (<a href="/books/NBK1306/table/edm.T.notable_slc26a2_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobedmTnotableslc26a2pathogenicvariant">p.Arg279Trp</a>, <a href="/books/NBK1306/table/edm.T.notable_slc26a2_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobedmTnotableslc26a2pathogenicvariant">c.-26+2T>C</a>, <a href="/books/NBK1306/table/edm.T.notable_slc26a2_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobedmTnotableslc26a2pathogenicvariant">p.Arg178Ter</a>, and <a href="/books/NBK1306/table/edm.T.notable_slc26a2_pathogenic_variant/?report=objectonly" target="object" rid-ob="figobedmTnotableslc26a2pathogenicvariant">p.Cys653Ser</a>) account for approximately 70% of disease alleles in all <i>SLC26A2</i>-related dysplasias. Targeted analysis of these four variants identified at least one pathogenic variant in nearly 100% of individuals with <i>SLC26A2</i>-MED (80% of individuals with <i>SLC26A2</i>-MED have two of the most common pathogenic variants, and another 16% have one common pathogenic variant in compound heterozygosity with another pathogenic variant).</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="edm.TF.1.5"><p class="no_margin">
|
|
<a class="bibr" href="#edm.REF.rossi.2001.159" rid="edm.REF.rossi.2001.159">Rossi & Superti-Furga [2001]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="edm.TF.1.6"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.</p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="edm.TF.1.7"><p class="no_margin">Data derived from the subscription-based professional view of Human Gene Mutation Database [<a class="bibr" href="#edm.REF.stenson.2020.1197" rid="edm.REF.stenson.2020.1197">Stenson et al 2020</a>]</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobedmTslc26a2skeletaldisorderspectrum"><div id="edm.T.slc26a2_skeletal_disorder_spectrum" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p><i>SLC26A2</i> Skeletal Disorder Spectrum</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1306/table/edm.T.slc26a2_skeletal_disorder_spectrum/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__edm.T.slc26a2_skeletal_disorder_spectrum_lrgtbl__"><table><thead><tr><th id="hd_h_edm.T.slc26a2_skeletal_disorder_spectrum_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder</th><th id="hd_h_edm.T.slc26a2_skeletal_disorder_spectrum_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_edm.T.slc26a2_skeletal_disorder_spectrum_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/achon1b/?report=reader">Achondrogenesis type 1B</a>
|
|
</td><td headers="hd_h_edm.T.slc26a2_skeletal_disorder_spectrum_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<ul><li class="half_rhythm"><div>Extremely short limbs w/short fingers & toes; hypoplasia of the thorax; & protuberant abdomen</div></li><li class="half_rhythm"><div>Hydropic fetal appearance caused by the abundance of soft tissue relative to the short skeleton</div></li><li class="half_rhythm"><div>Death occurs prenatally or shortly after birth</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_edm.T.slc26a2_skeletal_disorder_spectrum_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/ao2/?report=reader">Atelosteogenesis type 2</a>
|
|
</td><td headers="hd_h_edm.T.slc26a2_skeletal_disorder_spectrum_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<ul><li class="half_rhythm"><div>Commonly lethal in perinatal period</div></li><li class="half_rhythm"><div>Presents around birth or before</div></li><li class="half_rhythm"><div>Chondrodysplasia w/clinical & histologic characteristics resembling those of DTD but more pronounced</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_edm.T.slc26a2_skeletal_disorder_spectrum_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/diastrophic-d/?report=reader">Diastrophic dysplasia</a> (DTD)</td><td headers="hd_h_edm.T.slc26a2_skeletal_disorder_spectrum_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<ul><li class="half_rhythm"><div>Short limb type of dwarfism assoc w/clubfeet & other joint restrictions incl "hitchhiker thumbs"</div></li><li class="half_rhythm"><div>Progressive scoliosis in childhood</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_edm.T.slc26a2_skeletal_disorder_spectrum_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>SLC26A2</i>-related multiple epiphyseal dysplasia</td><td headers="hd_h_edm.T.slc26a2_skeletal_disorder_spectrum_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Topic of this <i>GeneReview</i></td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobedmTautosomaldominantmultipleepiphy"><div id="edm.T.autosomal_dominant_multiple_epiphy" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Autosomal Dominant Multiple Epiphyseal Dysplasia *</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1306/table/edm.T.autosomal_dominant_multiple_epiphy/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__edm.T.autosomal_dominant_multiple_epiphy_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_edm.T.autosomal_dominant_multiple_epiphy_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_edm.T.autosomal_dominant_multiple_epiphy_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical Features</th></tr></thead><tbody><tr><td headers="hd_h_edm.T.autosomal_dominant_multiple_epiphy_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>COL9A1</i>
|
|
</td><td headers="hd_h_edm.T.autosomal_dominant_multiple_epiphy_1_1_1_2" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/edm-ad/?report=reader"><i>COL9A1</i>-, <i>COL9A2</i>-, & <i>COL9A3</i>-MED</a> appear to have more severe knee involvement but relative sparing of the hips, resulting in a milder course than MED assoc w/<i>COMP</i> or <i>SLC26A2</i> pathogenic variants.</td></tr><tr><td headers="hd_h_edm.T.autosomal_dominant_multiple_epiphy_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>COL9A2</i>
|
|
</td></tr><tr><td headers="hd_h_edm.T.autosomal_dominant_multiple_epiphy_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>COL9A3</i>
|
|
</td></tr><tr><td headers="hd_h_edm.T.autosomal_dominant_multiple_epiphy_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>COMP</i>
|
|
</td><td headers="hd_h_edm.T.autosomal_dominant_multiple_epiphy_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/edm-ad/?report=reader"><i>COMP</i>-MED</a> is usually assoc w/significant involvement at the capital femoral epiphyses & irregular acetabula. <sup>1</sup></td></tr><tr><td headers="hd_h_edm.T.autosomal_dominant_multiple_epiphy_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>MATN3</i>
|
|
</td><td headers="hd_h_edm.T.autosomal_dominant_multiple_epiphy_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><a href="/books/n/gene/edm-ad/?report=reader"><i>MATN3</i>-MED</a> appears to be the mildest form of MED identified to date & is assoc w/a high degree of intrafamilial variability.</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">* See <a href="/books/n/gene/edm-ad/?report=reader">Multiple Epiphyseal Dysplasia, Autosomal Dominant</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">MED = multiple epiphyseal dysplasia</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="edm.TF.3.1"><p class="no_margin">Pathogenic variants in <i>COMP</i> are also associated with the more severe disorder <a href="/books/n/gene/psach/?report=reader">pseudoachondroplasia</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobedmmolgenTA"><div id="edm.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>SLC26A2-Related Multiple Epiphyseal Dysplasia: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1306/table/edm.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__edm.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_edm.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_edm.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_edm.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_edm.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_edm.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_edm.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/1836" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>SLC26A2</i>
|
|
</a>
|
|
</td><td headers="hd_b_edm.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=1836" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">5q32</a>
|
|
</td><td headers="hd_b_edm.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/P50443" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Sulfate transporter</a>
|
|
</td><td headers="hd_b_edm.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=SLC26A2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SLC26A2</a>
|
|
</td><td headers="hd_b_edm.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=SLC26A2[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SLC26A2</a>
|
|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="edm.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
|
|
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
|
chromosome locus from
|
|
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
|
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
|
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
|
<a href="/books/n/gene/app1/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobedmmolgenTB"><div id="edm.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for SLC26A2-Related Multiple Epiphyseal Dysplasia (<a href="/omim/226900,606718" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1306/table/edm.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__edm.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/226900" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">226900</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">EPIPHYSEAL DYSPLASIA, MULTIPLE, 4; EDM4</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/606718" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">606718</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SOLUTE CARRIER FAMILY 26 (SULFATE TRANSPORTER), MEMBER 2; SLC26A2</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobedmTnotableslc26a2pathogenicvariant"><div id="edm.T.notable_slc26a2_pathogenic_variant" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Notable <i>SLC26A2</i> Pathogenic Variants</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1306/table/edm.T.notable_slc26a2_pathogenic_variant/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__edm.T.notable_slc26a2_pathogenic_variant_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change<br />(Alias <sup>1</sup>)</th><th id="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change<br />(Alias <sup>1</sup>)</th><th id="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000112.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000112<wbr style="display:inline-block"></wbr>​.3</a>
|
|
</td><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.-26+2T>C</td><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in Finland; only variant that has been identified in all 4 <i>SLC26A2</i>-related dysplasias, in compound heterozygosity w/mild (<i>SLC26A2</i>-MED & <a href="/books/n/gene/diastrophic-d/?report=reader">DTD</a>) or severe (<a href="/books/n/gene/ao2/?report=reader">AO2</a> & <a href="/books/n/gene/achon1b/?report=reader">ACG1B</a>) alleles [<a class="bibr" href="#edm.REF.dwyer.2010.3043" rid="edm.REF.dwyer.2010.3043">Dwyer et al 2010</a>]</td></tr><tr><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_1" rowspan="6" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000112.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000112<wbr style="display:inline-block"></wbr>​.3</a>
|
|
<br />
|
|
<a href="https://www.ncbi.nlm.nih.gov/protein/NP_000103.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000103<wbr style="display:inline-block"></wbr>​.2</a>
|
|
</td><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.532C>T<br />(559C>T)</td><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg178Ter</td><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Second most common variant (9% of alleles); assoc w/more severe DTD phenotype or perinatal-lethal AO2, esp when combined in trans w/variant p.Arg279Trp</td></tr><tr><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.835C>T<br />(c.862C>T)</td><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg279Trp</td><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Most common variant found outside of Finland (45% of alleles); mild <i>SLC26A2</i>-MED when homozygous & mostly DTD & AO2 when found in compound heterozygous state [<a class="bibr" href="#edm.REF.barbosa.2011.550" rid="edm.REF.barbosa.2011.550">Barbosa et al 2011</a>]</td></tr><tr><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1020_1022delTGT<br />(1045-1047delGTT)</td><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Val341del</td><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_4" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="#edm.Molecular_Pathogenesis">Molecular Pathogenesis</a>.</td></tr><tr><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1361A>C<br />(1388A>C)</td><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gln454Pro</td></tr><tr><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1957T>A<br />(1984T>A)</td><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Cys653Ser</td><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Third most common variant (8% of alleles); <i>SLC26A2</i>-MED when homozygous & <i>SLC26A2</i>-MED or DTD when present in <i>trans</i> w/other pathogenic variants [<a class="bibr" href="#edm.REF.czarnyratajczak.2010.3036" rid="edm.REF.czarnyratajczak.2010.3036">Czarny-Ratajczak et al 2010</a>]</td></tr><tr><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.2033G>T<br />(2060G>T)</td><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly678Val</td><td headers="hd_h_edm.T.notable_slc26a2_pathogenic_variant_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="#edm.Molecular_Pathogenesis">Molecular Pathogenesis</a>.</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">ACG1B = achondrogenesis type 1B; AO2 = atelosteogenesis type 2; DTD = diastrophic dysplasia; MED = multiple epiphyseal dysplasia</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="edm.TF.4.1"><p class="no_margin">Variant designation that does not conform to current naming conventions</p></div></dd></dl></dl></div></div></div></article><article data-type="fig" id="figobedmF1"><div id="edm.F1" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK1306/bin/edm-Image001.jpg" alt="Figure 1. " /></div><h3><span class="label">Figure 1. </span></h3><div class="caption"><p>Double-layered patella</p><p><a class="bibr" href="#edm.REF.ballhausen.2003.65" rid="edm.REF.ballhausen.2003.65">Ballhausen et al [2003]</a>; reprinted with permission from the BMJ Publishing Group</p></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
|
|
|
|
|
|
|
|
|
|
<!-- Book content -->
|
|
|
|
<script type="text/javascript" src="/portal/portal3rc.fcgi/rlib/js/InstrumentNCBIBaseJS/InstrumentPageStarterJS.js"> </script>
|
|
|
|
|
|
<!-- CE8B5AF87C7FFCB1_0191SID /projects/books/PBooks@9.11 portal106 v4.1.r689238 Tue, Oct 22 2024 16:10:51 -->
|
|
<span id="portal-csrf-token" style="display:none" data-token="CE8B5AF87C7FFCB1_0191SID"></span>
|
|
|
|
<script type="text/javascript" src="//static.pubmed.gov/portal/portal3rc.fcgi/4216699/js/3968615.js" snapshot="books"></script></body>
|
|
</html>
|