218 lines
76 KiB
Text
218 lines
76 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="NBK45014">
|
|
<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="/NBK45014/?report=reader">
|
|
<meta name="ncbi_pagename" content="DNM2-Related Intermediate Charcot-Marie-Tooth Neuropathy – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY - GeneReviews® - NCBI Bookshelf"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>DNM2-Related Intermediate Charcot-Marie-Tooth Neuropathy – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY - GeneReviews® - NCBI Bookshelf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/dnajc6-pd/?report=reader">
|
|
<meta name="jr-next-unit" content="/books/n/gene/dnmt1-ddsn/?report=reader">
|
|
<meta name="bk-toc-url" content="/books/n/gene/?report=toc">
|
|
<meta name="robots" content="NOINDEX,NOFOLLOW,NOARCHIVE">
|
|
<meta name="citation_inbook_title" content="GeneReviews® [Internet]">
|
|
<meta name="citation_title" content="DNM2-Related Intermediate Charcot-Marie-Tooth Neuropathy – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY">
|
|
<meta name="citation_publisher" content="University of Washington, Seattle">
|
|
<meta name="citation_date" content="2015/06/25">
|
|
<meta name="citation_author" content="Stephan Züchner">
|
|
<meta name="citation_author" content="Feifei Tao">
|
|
<meta name="citation_pmid" content="20614582">
|
|
<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK45014/">
|
|
<meta name="citation_keywords" content="Dominant Intermediate Charcot-Marie-Tooth Neuropathy Type B (DI-CMTB)">
|
|
<meta name="citation_keywords" content="DI-CMTB">
|
|
<meta name="citation_keywords" content="Dominant Intermediate Charcot-Marie-Tooth Neuropathy Type B">
|
|
<meta name="citation_keywords" content="Dynamin-2">
|
|
<meta name="citation_keywords" content="DNM2">
|
|
<meta name="citation_keywords" content="DNM2-Related Intermediate Charcot-Marie-Tooth Neuropathy">
|
|
<link rel="schema.DC" href="http://purl.org/DC/elements/1.0/">
|
|
<meta name="DC.Title" content="DNM2-Related Intermediate Charcot-Marie-Tooth Neuropathy – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY">
|
|
<meta name="DC.Type" content="Text">
|
|
<meta name="DC.Publisher" content="University of Washington, Seattle">
|
|
<meta name="DC.Contributor" content="Stephan Züchner">
|
|
<meta name="DC.Contributor" content="Feifei Tao">
|
|
<meta name="DC.Date" content="2015/06/25">
|
|
<meta name="DC.Identifier" content="https://www.ncbi.nlm.nih.gov/books/NBK45014/">
|
|
<meta name="description" content="NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.">
|
|
<meta name="og:title" content="DNM2-Related Intermediate Charcot-Marie-Tooth Neuropathy – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY">
|
|
<meta name="og:type" content="book">
|
|
<meta name="og:description" content="NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.">
|
|
<meta name="og:url" content="https://www.ncbi.nlm.nih.gov/books/NBK45014/">
|
|
<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="warning" content="This publication is provided for historical reference only and the information may be out of date.">
|
|
<meta name="bk-non-canon-loc" content="/books/n/gene/cmt-dib/?report=reader">
|
|
<link rel="canonical" href="https://www.ncbi.nlm.nih.gov/books/NBK45014/">
|
|
<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">.main-content {background:transparent repeat-y top left;background-image:url(/corehtml/pmc/css/bookshelf/2.26/img/archive.png);background-size: auto, contain; padding:0 0 0 3em }</style>
|
|
<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="CE8BBD867D38C1A10000000000E500C1.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/NBK45014/?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/dnajc6-pd/?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">DNM2-Related Intermediate Charcot-Marie-Tooth Neuropathy – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY</div><div class="j">GeneReviews® [Internet]</div></div><div class="tail"><a href="/books/n/gene/dnmt1-ddsn/?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/NBK45014/"><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/NBK45014/&text=DNM2-Related%20Intermediate%20Charcot-Marie-Tooth%20Neuropathy%20%02013%20RETIRED%20CHAPTER%2C%20FOR%20HISTORICAL%20REFERENCE%20O..."><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/NBK45014/?report=classic">Switch to classic view</a><a href="/books/NBK45014/pdf/Bookshelf_NBK45014.pdf">PDF (441K)</a><a href="/books/NBK45014/?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%20NBK45014%20%2F%20sid%3ACE8B5AF87C7FFCB1_0191SID%20%2F%20phid%3ACE8BBD867D38C1A10000000000E500C1.4">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"><p class="vip-notice retraction"><strong>This publication is provided for historical reference only and the information may be out of date.</strong></p><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="_NBK45014_"><span class="title" itemprop="name"><i>DNM2</i>-Related Intermediate Charcot-Marie-Tooth Neuropathy – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: Dominant Intermediate Charcot-Marie-Tooth Neuropathy Type B (DI-CMTB)</div><p class="contribs">Züchner S, Tao F.</p><p class="fm-aai"><a href="#_NBK45014_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 12 minutes</em></p></div></div><div class="body-content whole_rhythm" itemprop="text"><div id="cmt-dib.Summary" itemprop="description"><h2 id="_cmt-dib_Summary_">Summary</h2><p>
|
|
<b>NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.</b>
|
|
</p><div><h4 class="inline">Clinical characteristics.</h4><p><i>DNM2-</i>related intermediate Charcot-Marie-Tooth neuropathy (DI-CMTB) has a classic, mild to moderately severe Charcot-Marie-Tooth hereditary neuropathy phenotype that often includes <i>pes cavus</i> foot deformity, depressed tendon reflexes, distal muscle weakness and atrophy, and sensory loss. Age of onset varies greatly among affected individuals and ranges from age two to 50 years. It is unusual for individuals with DI-CMTB to become wheelchair bound. Other findings include asymptomatic neutropenia and early-onset cataracts (often noted in childhood before age 15 years).</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis is suspected in individuals with typical findings of CMT hereditary neuropathy and intermediate or axonal motor median nerve conduction velocities (NCV) ranging from 26 m/s to normal. Diagnosis requires identification of a heterozygous pathogenic variant in <i>DNM2</i>, the only gene known to be associated with DI-CMTB.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Treatment of DI-CMTB is symptomatic and involves evaluation and management by a multidisciplinary team that includes neurologists, orthopedic surgeons, and physical and occupational therapists. Treatment may include ankle/foot orthoses, orthopedic surgery, forearm crutches or canes, wheelchairs, acetaminophen or nonsteroidal anti-inflammatory agents (NSAIDs) for musculoskeletal pain, and career and employment counseling.</p><p><i>Prevention of secondary complications:</i> Physical therapy to prevent foot contractures, acquired foot deformities, and difficulty walking.</p><p><i>Surveillance:</i> Regular evaluation by the multidisciplinary team to determine neurologic status and functional disability.</p><p><i>Pregnancy management</i>: In general there appears to be an increased occurrence of abnormal fetal presentation and maternal postpartum bleeding in women with Charcot-Marie-Tooth disease.</p><p><i>Agents/circumstances to avoid:</i> All drugs or agents known to be hazardous for peripheral neuropathies.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>DI-CMTB is inherited in an autosomal dominant manner. Most individuals diagnosed with DI-CMTB have an affected parent. The proportion of cases caused by a heterozygous <i>de novo</i> pathogenic variant is unknown. Each child of an individual with DI-CMTB has a 50% chance of inheriting the pathogenic variant. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant has been identified in an affected family member. Requests for prenatal testing for conditions which (like DI-CMTB) do not affect intellect and have some treatment available are not common.</p></div></div><div id="cmt-dib.Diagnosis"><h2 id="_cmt-dib_Diagnosis_">Diagnosis</h2><div id="cmt-dib.Suggestive_Findings"><h3>Suggestive Findings</h3><p><i>DNM2-</i>related intermediate Charcot-Marie-Tooth neuropathy (DI-CMTB) <b>should be suspected</b> in individuals with the following clinical findings, nerve conduction velocities, and neuropathology:</p><p>
|
|
<b>Clinical manifestations</b>
|
|
</p><ul><li class="half_rhythm"><div>Sensory and motor deficiencies involving the lower legs</div><ul><li class="half_rhythm"><div>Sensory loss</div></li><li class="half_rhythm"><div>Depressed tendon reflexes</div></li><li class="half_rhythm"><div>Distal muscle weakness and atrophy</div></li><li class="half_rhythm"><div><i>Pes cavus</i> foot deformity</div></li></ul></li><li class="half_rhythm"><div>Asymptomatic neutropenia</div></li><li class="half_rhythm"><div>Early-onset cataracts (noted before age 15 years)</div></li></ul><p><b>Nerve conduction velocities (NCVs)</b> are "intermediate" (i.e., 25-45 m/s) between a demyelinating and axonal neuropathy using strict electrophysiologic criteria [<a class="bibr" href="#cmt-dib.REF.davis.1978.311" rid="cmt-dib.REF.davis.1978.311">Davis et al 1978</a>, <a class="bibr" href="#cmt-dib.REF.nicholson.2006.123" rid="cmt-dib.REF.nicholson.2006.123">Nicholson & Myers 2006</a>].</p><p><b>Neuropathology.</b> Sural nerve biopsy has shown diffuse loss of large myelinated fibers, clusters of regenerating myelinated axons, and fibers with focal myelin thickenings [<a class="bibr" href="#cmt-dib.REF.kennerson.2001.883" rid="cmt-dib.REF.kennerson.2001.883">Kennerson et al 2001</a>, <a class="bibr" href="#cmt-dib.REF.claeys.2009.1741" rid="cmt-dib.REF.claeys.2009.1741">Claeys et al 2009</a>].</p></div><div id="cmt-dib.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of DI-CMTB <b>is established</b> in a proband by the identification of a heterozygous pathogenic variant in <i>DNM2</i>.</p><p>Molecular testing approaches can include <b>serial single-gene testing</b>, use of a <b>multigene panel</b>, and <b>comprehensive genomic testing</b>.</p><p><b>Serial single-gene testing</b> can be considered based on the order in which pathogenic variants most commonly occur in individuals with the above suggestive findings:</p><ul><li class="half_rhythm"><div>In a person with a CMT phenotype and very slow NCV (<30 m/s), perform molecular genetic testing of <i>PMP22</i> first to determine if a <i>PMP22</i> duplication, the most common cause of this demyelinating phenotype, is present.</div></li><li class="half_rhythm"><div>In a person with a CMT phenotype and intermediate to normal NCV, perform molecular genetic testing of the <i>MPZ</i>, <i>GJB1</i> (encoding the protein connexin 32), and <i>MFN2</i> genes first because mutation of one of these genes is a common cause of this phenotype.</div></li><li class="half_rhythm"><div>In a person with a CMT phenotype and NCV between 30 and 45 m/s in whom testing for the above genes has not identified a pathogenic variant, molecular genetic testing of <i>DNM2</i> is appropriate.</div></li></ul><p><b>A multigene panel</b> that includes <i>DNM2</i> and other genes of interest (see <a href="#cmt-dib.Genetically_Related_Allelic_Diso">Differential Diagnosis</a>) may also be considered. 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>; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (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><p><b>Comprehensive genomic testing</b> may be considered if serial single-gene testing (and/or use of a multigene panel) has not confirmed a diagnosis in an individual with features of DI-CMTB. Such testing may include exome sequencing, genome sequencing, and mitochondrial sequencing.</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="figcmtdibTmoleculargenetictestingused"><a href="/books/NBK45014/table/cmt-dib.T.molecular_genetic_testing_used/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobcmtdibTmoleculargenetictestingused"><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="cmt-dib.T.molecular_genetic_testing_used"><a href="/books/NBK45014/table/cmt-dib.T.molecular_genetic_testing_used/?report=objectonly" target="object" rid-ob="figobcmtdibTmoleculargenetictestingused">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in <i>DNM2-</i>Related Intermediate Charcot-Marie-Tooth Neuropathy </p></div></div></div></div><div id="cmt-dib.Clinical_Characteristics"><h2 id="_cmt-dib_Clinical_Characteristics_">Clinical Characteristics</h2><div id="cmt-dib.Clinical_Description"><h3>Clinical Description</h3><p><i>DNM2-</i>related intermediate Charcot-Marie-Tooth neuropathy (DI-CMTB) is a so-called "dominant intermediate form" of CMT neuropathy because it is inherited in an autosomal dominant manner and it is "intermediate" between a demyelinating and axonal neuropathy using strict electrophysiologic criteria for nerve conduction velocities (NCVs). The condition is characterized by a classic, mild to moderately severe Charcot-Marie-Tooth hereditary neuropathy phenotype that often includes <i>pes cavus</i> foot deformity, depressed tendon reflexes, distal muscle weakness and atrophy, and sensory loss.</p><p>Age of onset varies greatly among affected individuals and ranges from age two to 50 years. Some persons require AFO braces or other walking aids. Three percent of affected individuals become wheelchair bound; one person in the <a class="bibr" href="#cmt-dib.REF.claeys.2009.1741" rid="cmt-dib.REF.claeys.2009.1741">Claeys et al [2009]</a> study required a wheelchair at age 61 years.</p><p>Other findings include asymptomatic neutropenia and early-onset cataracts (often noted in childhood before age 15 years).</p><p>Electrophysiologic studies indicate intermediate or axonal motor median nerve conduction velocities (NCV) ranging from 26 m/s to normal values.</p></div><div id="cmt-dib.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>Strong genotype-phenotype correlations have not been reported.</p><p>The majority of <i>DNM2</i> pathogenic variants appear to be in the domain encoding homology to pleckstrin [<a class="bibr" href="#cmt-dib.REF.z_chner.2005.289" rid="cmt-dib.REF.z_chner.2005.289">Züchner et al 2005</a>, <a class="bibr" href="#cmt-dib.REF.fabrizi.2007.291" rid="cmt-dib.REF.fabrizi.2007.291">Fabrizi et al 2007</a>]; however, exceptions have been identified [<a class="bibr" href="#cmt-dib.REF.claeys.2009.1741" rid="cmt-dib.REF.claeys.2009.1741">Claeys et al 2009</a>, <a class="bibr" href="#cmt-dib.REF.susman.2010.229" rid="cmt-dib.REF.susman.2010.229">Susman et al 2010</a>].</p></div><div id="cmt-dib.Penetrance"><h3>Penetrance</h3><p><i>DNM2</i> pathogenic variants are penetrant over a wide range of ages (age 2-50 years) [<a class="bibr" href="#cmt-dib.REF.claeys.2009.1741" rid="cmt-dib.REF.claeys.2009.1741">Claeys et al 2009</a>, <a class="bibr" href="#cmt-dib.REF.haberlov_.2011.182" rid="cmt-dib.REF.haberlov_.2011.182">Haberlová et al 2011</a>].</p></div><div id="cmt-dib.Anticipation"><h3>Anticipation</h3><p>Anticipation is not observed.</p></div><div id="cmt-dib.Prevalence"><h3>Prevalence</h3><p>DI-CMTB is a rare cause of CMT. Up to 3.4% of CMT (in which CMT1A, 1B, and 1X have already been excluded) is caused by a <i>DNM2</i> pathogenic variant [<a class="bibr" href="#cmt-dib.REF.claeys.2009.1741" rid="cmt-dib.REF.claeys.2009.1741">Claeys et al 2009</a>].</p></div></div><div id="cmt-dib.Genetically_Related_Allelic_Diso"><h2 id="_cmt-dib_Genetically_Related_Allelic_Diso_">Genetically Related (Allelic) Disorders</h2><p><b>Charcot-Marie-Tooth Type 2M (CMT2M)</b> is a purely axonal CMT caused by heterozygous pathogenic variants in <i>DNM2</i>; it is distinguished from DI-CMT by the lack of demyelinating changes. CMT2M is inherited in an autosomal dominant manner [<a class="bibr" href="#cmt-dib.REF.fabrizi.2007.291" rid="cmt-dib.REF.fabrizi.2007.291">Fabrizi et al 2007</a>].</p><p><b>Autosomal dominant centronuclear myopathy</b> (<i>DNM2</i>-related CNM) is also associated with pathogenic variants in <i>DNM2</i> [<a class="bibr" href="#cmt-dib.REF.bitoun.2005.1207" rid="cmt-dib.REF.bitoun.2005.1207">Bitoun et al 2005</a>]. <i>DNM2</i>-related CNM usually presents with neonatal hypotonia, weak suck, poor feeding, and progressive muscle weakness with respiratory problems [<a class="bibr" href="#cmt-dib.REF.jungbluth.2010.49" rid="cmt-dib.REF.jungbluth.2010.49">Jungbluth et al 2010</a>, <a class="bibr" href="#cmt-dib.REF.melberg.2010.53" rid="cmt-dib.REF.melberg.2010.53">Melberg et al 2010</a>].</p><p>Some individuals with CNM have clinical findings that overlap with DI-CMTB [<a class="bibr" href="#cmt-dib.REF.fischer.2006.1463" rid="cmt-dib.REF.fischer.2006.1463">Fischer et al 2006</a>, <a class="bibr" href="#cmt-dib.REF.bitoun.2008.334" rid="cmt-dib.REF.bitoun.2008.334">Bitoun et al 2008</a>, <a class="bibr" href="#cmt-dib.REF.susman.2010.229" rid="cmt-dib.REF.susman.2010.229">Susman et al 2010</a>]. The findings shared between DI-CMTB and CNM are muscle weakness and sometimes cataract. CNM does not have peripheral nerve involvement and often has proximal muscle weakness that is not seen in DI-CMTB.</p></div><div id="cmt-dib.Differential_Diagnosis"><h2 id="_cmt-dib_Differential_Diagnosis_">Differential Diagnosis</h2><p>Other forms of intermediate CMT:</p><ul><li class="half_rhythm"><div>DI-CMTA, linked to the 10q24-q25.1 region</div></li><li class="half_rhythm"><div>DI-CMTC, caused by heterozygous pathogenic variants in <i>YARS1</i> (formerly <i>TyrRS</i>)</div></li><li class="half_rhythm"><div>DI-CMTD, caused by heterozygous pathogenic variants in <i>MPZ</i></div></li><li class="half_rhythm"><div><i>GNB4</i>-related CMT, also inherited in an autosomal dominant manner</div></li></ul><p>It is usually not possible to differentiate between DI-CMTB, other intermediate forms of CMT, and most CMT2 types based on clinical findings [<a class="bibr" href="#cmt-dib.REF.nicholson.2006.123" rid="cmt-dib.REF.nicholson.2006.123">Nicholson & Myers 2006</a>], unless cataract and/or neutropenia (occasional findings in DI-CMTB) are present.</p><p>See <a href="/books/n/gene/cmt/?report=reader">CMT Overview</a>, particularly to exclude potentially treatable causes of acquired neuropathy.</p></div><div id="cmt-dib.Management"><h2 id="_cmt-dib_Management_">Management</h2><div id="cmt-dib.Evaluations_Following_Initial_Di"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with <i>DNM2-</i>related intermediate Charcot-Marie-Tooth neuropathy (DI-CMTB), the following evaluations are recommended:</p><ul><li class="half_rhythm"><div>Neurologic examination</div></li><li class="half_rhythm"><div>Electrophysiologic studies to establish a baseline for further monitoring of disease progression</div></li><li class="half_rhythm"><div>Complete blood count (CBC) with absolute neutrophil count (ANC) to evaluate for neutropenia</div></li><li class="half_rhythm"><div>Ophthalmologic examination for cataract</div></li><li class="half_rhythm"><div>Consultation with a clinical geneticist and/or genetic counselor</div></li></ul></div><div id="cmt-dib.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Treatment of DI-CMTB is symptomatic and involves evaluation and management by a multidisciplinary team that includes neurologists, orthopedic surgeons, and physical and occupational therapists. Due to the great phenotypic variability, disease treatment should be tailored to the individual's needs.</p><p>Treatment may include:</p><ul><li class="half_rhythm"><div>Ankle/foot orthoses</div></li><li class="half_rhythm"><div>Orthopedic surgery</div></li><li class="half_rhythm"><div>Forearm crutches or canes; rarely, wheelchairs</div></li><li class="half_rhythm"><div>Treatment of musculoskeletal pain with acetaminophen or nonsteroidal anti-inflammatory agents (NSAIDs)</div></li><li class="half_rhythm"><div>Career and employment counseling</div></li></ul></div><div id="cmt-dib.Prevention_of_Secondary_Complica"><h3>Prevention of Secondary Complications</h3><p>The most common secondary complications include foot contractures and acquired foot deformities, difficulty walking, and, in severe cases, inability to ambulate. Physical therapies such as stretching and exercise are recommended to prevent these secondary complications.</p></div><div id="cmt-dib.Surveillance"><h3>Surveillance</h3><p>Surveillance includes regular evaluation by the multidisciplinary team to determine neurologic status and functional disability.</p></div><div id="cmt-dib.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Medications that are toxic or potentially toxic to persons with CMT comprise a spectrum of risk ranging from definite high risk to negligible risk. See the Charcot-Marie-Tooth Association <a href="https://www.cmtausa.org/living-with-cmt/managing-cmt/medications/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">website</a> (pdf) for an up-to-date list.</p></div><div id="cmt-dib.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#cmt-dib.Related_Genetic_Counseling_Issue">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="cmt-dib.Pregnancy_Management"><h3>Pregnancy Management</h3><p>Although no systemic studies have been done concerning pregnancy in women with DI-CMTB, there are reports of an increased occurrence of abnormal fetal presentation and maternal postpartum bleeding in women with CMT in general [<a class="bibr" href="#cmt-dib.REF.hoff.2005.459" rid="cmt-dib.REF.hoff.2005.459">Hoff et al 2005</a>]. The early miscarriage rate is <b>not</b> increased in women with CMT [<a class="bibr" href="#cmt-dib.REF.argov.2009.675" rid="cmt-dib.REF.argov.2009.675">Argov & de Visser 2009</a>].</p></div><div id="cmt-dib.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <a href="http://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="http://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="cmt-dib.Genetic_Counseling"><h2 id="_cmt-dib_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="cmt-dib.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p><i>DNM2-</i>related intermediate Charcot-Marie-Tooth neuropathy (DI-CMTB) is inherited in an autosomal dominant manner.</p></div><div id="cmt-dib.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
|
|
<b>Parents of a proband</b>
|
|
</p><ul><li class="half_rhythm"><div>Most individuals diagnosed with DI-CMTB have an affected parent.</div></li><li class="half_rhythm"><div>A proband with DI-CMTB may have the disorder as the result of <i>de novo</i>
|
|
<i>DNM2</i> mutation. The proportion of cases caused by a <i>de novo</i> pathogenic variant is unknown.</div></li><li class="half_rhythm"><div>If the pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, two possible explanations are germline mosaicism in a parent or <i>de novo</i> mutation in the proband. Although no instances of germline mosaicism have been reported, it remains a possibility.</div></li><li class="half_rhythm"><div>Recommendations for the evaluation of parents of a proband with an apparent <i>de novo</i> pathogenic variant include <i>DNM2</i> molecular genetic testing for the variant identified in the proband. Evaluation of parents may determine that one is affected but has escaped previous diagnosis because of failure by health care professionals to recognize the syndrome and/or a milder phenotypic presentation. Therefore, an apparently negative family history cannot be confirmed until appropriate evaluations have been performed.</div></li></ul><p>Note: (1) Although most individuals diagnosed with DI-CMTB have an affected parent, the family history may appear to be negative because of failure to recognize the disorder in family members, early death of the parent before the onset of symptoms, or late onset of the disease in the affected parent. (2) If the parent is the individual in whom the pathogenic variant first occurred s/he may have somatic mosaicism for the variant and may be mildly/minimally affected.</p><p>
|
|
<b>Sibs of a proband</b>
|
|
</p><ul><li class="half_rhythm"><div>The risk to the sibs of the proband depends on the genetic status of the proband's parents.</div></li><li class="half_rhythm"><div>If a parent of the proband is affected and/or has a pathogenic variant, the risk to the sibs of inheriting the variant is 50%.</div></li><li class="half_rhythm"><div>When the parents are clinically unaffected, the risk to the sibs of a proband appears to be low.</div></li><li class="half_rhythm"><div>The sibs of a proband with clinically unaffected parents are still at increased risk for DI-CMTB because of the possibility of reduced penetrance in a parent.</div></li><li class="half_rhythm"><div>If the pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, the empiric recurrence risk to sibs is approximately 1% because of the theoretic possibility of parental germline mosaicism.</div></li></ul><p><b>Offspring of a proband.</b> Each child of an individual with DI-CMTB has a 50% chance of inheriting the <i>DNM2</i> pathogenic variant.</p><p>
|
|
<b>Other family members</b>
|
|
</p><ul><li class="half_rhythm"><div>The risk to other family members depends on the status of the proband's parents.</div></li><li class="half_rhythm"><div>If a parent is affected and/or has a pathogenic variant, his or her family members may be at risk.</div></li></ul></div><div id="cmt-dib.Related_Genetic_Counseling_Issue"><h3>Related Genetic Counseling Issues</h3><p><b>Considerations in families with an apparent <i>de novo</i> pathogenic variant.</b> When neither parent of a proband with an autosomal dominant condition has clinical evidence of the disorder or the pathogenic variant, it is likely that the proband has a <i>de novo</i> pathogenic variant. However, possible non-medical explanations including alternate paternity or maternity (e.g., with assisted reproduction) or undisclosed adoption could also be explored.</p><p>
|
|
<b>Family planning</b>
|
|
</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal 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 or at risk of being affected.</div></li></ul><p><b>DNA banking</b> is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.</p></div><div id="cmt-dib.Prenatal_Testing_and_Preimplanta"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>DNM2</i> pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for <i>DNM2</i>-related intermediate Charcot-Marie-Tooth neuropathy are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. While most centers would consider decisions regarding prenatal testing to be the choice of the parents, discussion of these issues is appropriate.</p></div></div><div id="cmt-dib.Resources"><h2 id="_cmt-dib_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>Association CMT France</b>
|
|
</div><div>France</div><div><b>Phone:</b> 820 077 540; 2 47 27 96 41 </div><div>
|
|
<a href="http://www.cmt-france.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.cmt-france.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Charcot-Marie-Tooth Association (CMTA)</b>
|
|
</div><div>PO Box 105</div><div>Glenolden PA 19036</div><div><b>Phone:</b> 800-606-2682 (toll-free); 610-499-9264</div><div><b>Fax:</b> 610-499-9267</div><div><b>Email:</b> info@cmtausa.org</div><div>
|
|
<a href="http://www.cmtausa.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.cmtausa.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>European Charcot-Marie-Tooth Consortium</b>
|
|
</div><div>Department of Molecular Genetics</div><div>University of Antwerp</div><div>Antwerp Antwerpen B-2610</div><div>Belgium</div><div><b>Fax:</b> 03 2651002</div><div><b>Email:</b> gisele.smeyers@ua.ac.be</div></li><li class="half_rhythm"><div>
|
|
<b>Hereditary Neuropathy Foundation, Inc.</b>
|
|
</div><div>432 Park Avenue South</div><div>4th Floor</div><div>New York NY 10016</div><div><b>Phone:</b> 855-435-7268 (toll-free); 212-722-8396</div><div><b>Fax:</b> 917-591-2758</div><div><b>Email:</b> info@hnf-cure.org</div><div>
|
|
<a href="http://www.hnf-cure.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.hnf-cure.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>My46 Trait Profile</b>
|
|
</div><div>
|
|
<a href="https://www.my46.org/trait-document?trait=Charcot%20Marie%20Tooth%20disease&parent=Genetic%20Syndromes&type=profile" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Charcot Marie Tooth disease</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>National Library of Medicine Genetics Home Reference</b>
|
|
</div><div>
|
|
<a href="http://ghr.nlm.nih.gov/condition=charcotmarietoothdisease" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Charcot-Marie-Tooth disease</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>NCBI Genes and Disease</b>
|
|
</div><div>
|
|
<a href="/books/NBK22241/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Charcot-Marie-Tooth syndrome</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>TREAT-NMD</b>
|
|
</div><div>Institute of Genetic Medicine</div><div>University of Newcastle upon Tyne </div><div>International Centre for Life </div><div> Newcastle upon Tyne NE1 3BZ</div><div>United Kingdom</div><div><b>Phone:</b> 44 (0)191 241 8617</div><div><b>Fax:</b> 44 (0)191 241 8770</div><div><b>Email:</b> info@treat-nmd.eu</div><div>
|
|
<a href="http://www.treat-nmd.eu/cmt/overview/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Charcot-Marie-Tooth Disease</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Association Francaise contre les Myopathies (AFM)</b>
|
|
</div><div>1 Rue de l'International</div><div>BP59</div><div>Evry cedex 91002</div><div>France</div><div><b>Phone:</b> +33 01 69 47 28 28</div><div><b>Email:</b> dmc@afm.genethon.fr</div><div>
|
|
<a href="http://www.afm-telethon.fr" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.afm-telethon.fr </a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>European Neuromuscular Centre (ENMC)</b>
|
|
</div><div>Lt Gen van Heutszlaan 6</div><div>3743 JN Baarn</div><div>Netherlands</div><div><b>Phone:</b> 31 35 5480481</div><div><b>Fax:</b> 31 35 5480499</div><div><b>Email:</b> enmc@enmc.org</div><div>
|
|
<a href="http://www.enmc.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.enmc.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Muscular Dystrophy Association - USA (MDA)</b>
|
|
</div><div>222 South Riverside Plaza</div><div>Suite 1500</div><div>Chicago IL 60606</div><div><b>Phone:</b> 800-572-1717</div><div><b>Email:</b> mda@mdausa.org</div><div>
|
|
<a href="http://www.mda.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.mda.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>Muscular Dystrophy UK</b>
|
|
</div><div>61A Great Suffolk Street</div><div>London SE1 0BU </div><div>United Kingdom</div><div><b>Phone:</b> 0800 652 6352 (toll-free); 020 7803 4800</div><div><b>Email:</b> info@musculardystrophyuk.org</div><div>
|
|
<a href="http://www.musculardystrophyuk.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.musculardystrophyuk.org</a>
|
|
</div></li><li class="half_rhythm"><div>
|
|
<b>RDCRN Patient Contact Registry: Inherited Neuropathies Consortium</b>
|
|
</div><div>
|
|
<a href="https://www.rarediseasesnetwork.org/cms/inc" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Patient Contact Registry</a>
|
|
</div></li></ul>
|
|
</div><div id="cmt-dib.Molecular_Genetics"><h2 id="_cmt-dib_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="figcmtdibmolgenTA"><a href="/books/NBK45014/table/cmt-dib.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobcmtdibmolgenTA"><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="cmt-dib.molgen.TA"><a href="/books/NBK45014/table/cmt-dib.molgen.TA/?report=objectonly" target="object" rid-ob="figobcmtdibmolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">DNM2-Related Intermediate Charcot-Marie-Tooth Neuropathy: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcmtdibmolgenTB"><a href="/books/NBK45014/table/cmt-dib.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobcmtdibmolgenTB"><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="cmt-dib.molgen.TB"><a href="/books/NBK45014/table/cmt-dib.molgen.TB/?report=objectonly" target="object" rid-ob="figobcmtdibmolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for DNM2-Related Intermediate Charcot-Marie-Tooth Neuropathy (View All in OMIM) </p></div></div><p><b>Gene structure.</b>
|
|
<i>DNM2</i> has several isoforms; the longest transcript is isoform 1 (<a href="/protein/56549121" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_001005360.1</a>), which has 22 exons. See <a href="/gene/1785" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Entrez Gene</a> for a description of isoforms.</p><p><b>Pathogenic variants.</b> Pathogenic missense variants and small deletions in the coding region have been described.</p><p><b>Normal gene product</b>. Isoform 1 encodes the dynamin-2 protein of 870 amino acid residues (<a href="/protein/56549121" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_001005360.1</a>).</p><p><b>Abnormal gene product.</b> The identification of small deletions suggests that haploinsufficiency is the cause of the disorder.</p></div><div id="cmt-dib.References"><h2 id="_cmt-dib_References_">References</h2><div id="cmt-dib.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="cmt-dib.REF.argov.2009.675">Argov Z, de Visser M. What we do not know about pregnancy in hereditary neuromuscular disorders. <span><span class="ref-journal">Neuromuscul Disord. </span>2009;<span class="ref-vol">19</span>:675–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19692244" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19692244</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cmt-dib.REF.bitoun.2008.334">Bitoun M, Stojkovic T, Prudhon B, Maurage CA, Latour P, Vermersch P, Guicheney P. A novel mutation in the dynamin 2 gene in a Charcot-Marie-Tooth type 2 patient: clinical and pathological findings. <span><span class="ref-journal">Neuromuscul Disord. </span>2008;<span class="ref-vol">18</span>:334–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18394888" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18394888</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cmt-dib.REF.bitoun.2005.1207">Bitoun M, Maugenre S, Jeannet PY, Lacene E, Ferrer X, Laforet P, Martin JJ, Laporte J, Lochmuller H, Beggs AH, Fardeau M, Eymard B, Romero NB, Guicheney P. Mutations in Dynamin 2 cause dominant centronuclear myopathy. <span><span class="ref-journal">Nat Genet. </span>2005;<span class="ref-vol">37</span>:1207–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16227997" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16227997</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cmt-dib.REF.claeys.2009.1741">Claeys KG, Züchner S, Kennerson M, Berciano J, Garcia A, Verhoeven K, Storey E, Merory JR, Bienfait HM, Lammens M, Nelis E, Baets J, De Vriendt E, Berneman ZN, De Veuster I, Vance JM, Nicholson G, Timmerman V, De Jonghe P. Phenotypic spectrum of dynamin 2 mutations in Charcot-Marie-Tooth neuropathy. <span><span class="ref-journal">Brain. </span>2009;<span class="ref-vol">132</span>:1741–52.</span> [<a href="/pmc/articles/PMC2724916/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2724916</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19502294" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19502294</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cmt-dib.REF.davis.1978.311">Davis CJ, Bradley WG, Madrid R. The peroneal muscular atrophy syndrome: clinical, genetic, electrophysiological and nerve biopsy studies. I. Clinical, genetic and electrophysiological findings and classification. <span><span class="ref-journal">J Genet Hum. </span>1978;<span class="ref-vol">26</span>:311–49.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/752065" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 752065</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cmt-dib.REF.fabrizi.2007.291">Fabrizi GM, Ferrarini M, Cavallaro T, Cabrini I, Cerini R, Bertolasi L, Rizzuto N. Two novel mutations in dynamin-2 cause axonal Charcot-Marie-Tooth disease. <span><span class="ref-journal">Neurology. </span>2007;<span class="ref-vol">69</span>:291–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17636067" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17636067</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cmt-dib.REF.fischer.2006.1463">Fischer D, Herasse M, Bitoun M, Barragán-Campos HM, Chiras J, Laforêt P, Fardeau M, Eymard B, Guicheney P, Romero NB. Characterization of the muscle involvement in dynamin 2-related centronuclear myopathy. <span><span class="ref-journal">Brain. </span>2006;<span class="ref-vol">129</span>:1463–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16585051" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16585051</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cmt-dib.REF.haberlov_.2011.182">Haberlová J, Mazanec R, Ridzoň P, Baránková L, Nürnberg G, Nürnberg P, Sticht H, Huehne K, Seeman P, Rautenstrauss B. Phenotypic variability in a large Czech family with a dynamin 2-associated Charcot-Marie-Tooth neuropathy. <span><span class="ref-journal">J Neurogenet. </span>2011;<span class="ref-vol">25</span>:182–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22091729" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22091729</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cmt-dib.REF.hoff.2005.459">Hoff JM, Gilhus NE, Daltveit AK. Pregnancies and deliveries in patients with Charcot-Marie-Tooth disease. <span><span class="ref-journal">Neurology. </span>2005;<span class="ref-vol">64</span>:459–62.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15699375" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15699375</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cmt-dib.REF.jungbluth.2010.49">Jungbluth H, Cullup T, Lillis S, Zhou H, Abbs S, Sewry C, Muntoni F. Centronuclear myopathy with cataracts due to a novel dynamin 2 (DNM2) mutation. <span><span class="ref-journal">Neuromuscul Disord. </span>2010;<span class="ref-vol">20</span>:49–52.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19932620" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19932620</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cmt-dib.REF.kennerson.2001.883">Kennerson ML, Zhu D, Gardner RJ, Storey E, Merory J, Robertson SP, Nicholson GA. Dominant intermediate Charcot-Marie-Tooth neuropathy maps to chromosome 19p12-p13.2. <span><span class="ref-journal">Am J Hum Genet. </span>2001;<span class="ref-vol">69</span>:883–8.</span> [<a href="/pmc/articles/PMC1226074/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1226074</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/11533912" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11533912</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cmt-dib.REF.melberg.2010.53">Melberg A, Kretz C, Kalimo H, Wallgren-Pettersson C, Toussaint A, Böhm J, Stålberg E, Laporte J. Adult course in dynamin 2 dominant centronuclear myopathy with neonatal onset. <span><span class="ref-journal">Neuromuscul Disord. </span>2010;<span class="ref-vol">20</span>:53–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19932619" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19932619</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cmt-dib.REF.nicholson.2006.123">Nicholson G, Myers S. Intermediate forms of Charcot-Marie Tooth neuropathy: a review. <span><span class="ref-journal">Neuromolecular Med. </span>2006;<span class="ref-vol">8</span>:123–30.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16775371" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16775371</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cmt-dib.REF.susman.2010.229">Susman RD, Quijano-Roy S, Yang N, Webster R, Clarke NF, Dowling J, Kennerson M, Nicholson G, Biancalana V, Ilkovski B, Flanigan KM, Arbuckle S, Malladi C, Robinson P, Vucic S, Mayer M, Romero NB, Urtizberea JA, García-Bragado F, Guicheney P, Bitoun M, Carlier RY, North KN. Expanding the clinical, pathological and MRI phenotype of DNM2-related centronuclear myopathy. <span><span class="ref-journal">Neuromuscul Disord. </span>2010;<span class="ref-vol">20</span>:229–37.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20227276" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20227276</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cmt-dib.REF.z_chner.2005.289">Züchner S, Noureddine M, Kennerson M, Verhoeven K, Claeys K, De Jonghe P, Merory J, Oliveira SA, Speer MC, Stenger JE, Walizada G, Zhu D, Pericak-Vance MA, Nicholson G, Timmerman V, Vance JM. Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease. <span><span class="ref-journal">Nat Genet. </span>2005;<span class="ref-vol">37</span>:289–94.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15731758" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15731758</span></a>]</div></p></li></ul></div></div><div id="cmt-dib.Chapter_Notes"><h2 id="_cmt-dib_Chapter_Notes_">Chapter Notes</h2><div id="cmt-dib.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>19 September 2019 (ma) Chapter retired: Covered in <a href="/books/n/gene/cmt/?report=reader">Charcot-Marie-Tooth Hereditary Neuropathy Overview</a></div></li><li class="half_rhythm"><div>25 June 2015 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>8 July 2010 (me) Review posted live</div></li><li class="half_rhythm"><div>26 March 2010 (sz) Original submission</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK45014_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Stephan Züchner</span>, MD, PhD<div class="affiliation small">Professor for Human Genetics and Neurology<br />Dr John T Macdonald Foundation Department of Human Genetics and John P Hussman Institute for Human Genomics<br />University of Miami Miller School of Medicine<br />Miami, Florida<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.imaim.dem@renhcuzs" class="oemail">ude.imaim.dem@renhcuzs</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Feifei Tao</span>, MS<div class="affiliation small">Dr John T Macdonald Foundation Department of Human Genetics and John P Hussman Institute for Human Genomics<br />University of Miami Miller School of Medicine<br />Miami, Florida<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.imaim.dem@oat.f" class="oemail">ude.imaim.dem@oat.f</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">July 8, 2010</span>; Last Update: <span itemprop="dateModified">June 25, 2015</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>Züchner S, Tao F. DNM2-Related Intermediate Charcot-Marie-Tooth Neuropathy – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 2010 Jul 8 [Updated 2015 Jun 25]. 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/dnajc6-pd/?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/dnmt1-ddsn/?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="figobcmtdibTmoleculargenetictestingused"><div id="cmt-dib.T.molecular_genetic_testing_used" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in <i>DNM2-</i>Related Intermediate Charcot-Marie-Tooth Neuropathy</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK45014/table/cmt-dib.T.molecular_genetic_testing_used/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cmt-dib.T.molecular_genetic_testing_used_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cmt-dib.T.molecular_genetic_testing_used_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_cmt-dib.T.molecular_genetic_testing_used_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_cmt-dib.T.molecular_genetic_testing_used_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands with a Pathogenic Variant <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_cmt-dib.T.molecular_genetic_testing_used_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>DNM2</i>
|
|
</td><td headers="hd_h_cmt-dib.T.molecular_genetic_testing_used_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_cmt-dib.T.molecular_genetic_testing_used_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Nearly 100%</td></tr><tr><td headers="hd_h_cmt-dib.T.molecular_genetic_testing_used_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>4</sup></td><td headers="hd_h_cmt-dib.T.molecular_genetic_testing_used_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">None reported <sup>5</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="cmt-dib.TF.1.1"><p class="no_margin">See <a href="/books/NBK45014/?report=reader#cmt-dib.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="cmt-dib.TF.1.2"><p class="no_margin">See <a href="#cmt-dib.Molecular_Genetics">Molecular Genetics</a> for information on allelic variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="cmt-dib.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. 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="cmt-dib.TF.1.4"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and gene-targeted microarray designed to detect single-exon deletions or duplications.</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="cmt-dib.TF.1.5"><p class="no_margin">No deletions or duplications involving <i>DNM2</i> as causative of DI-CMTB have been reported.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcmtdibmolgenTA"><div id="cmt-dib.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>DNM2-Related Intermediate Charcot-Marie-Tooth Neuropathy: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK45014/table/cmt-dib.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cmt-dib.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_cmt-dib.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Locus Name</th><th id="hd_b_cmt-dib.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_cmt-dib.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_cmt-dib.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_cmt-dib.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_cmt-dib.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_cmt-dib.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_cmt-dib.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">DI-CMTB</td><td headers="hd_b_cmt-dib.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/1785" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>DNM2</i>
|
|
</a>
|
|
</td><td headers="hd_b_cmt-dib.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=1785" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">19p13<wbr style="display:inline-block"></wbr>​.2</a>
|
|
</td><td headers="hd_b_cmt-dib.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/P50570" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Dynamin-2</a>
|
|
</td><td headers="hd_b_cmt-dib.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.molgen.ua.ac.be/CMTMutations/Mutations/Contexts.cfm?ID=38" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">IPN Mutations, DNM2</a>
|
|
<br />
|
|
<a href="https://databases.lovd.nl/shared/genes/DNM2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">DNM2 homepage - Leiden Muscular Dystrophy pages</a>
|
|
</td><td headers="hd_b_cmt-dib.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=DNM2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">DNM2</a>
|
|
</td><td headers="hd_b_cmt-dib.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=DNM2[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">DNM2</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="cmt-dib.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="figobcmtdibmolgenTB"><div id="cmt-dib.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for DNM2-Related Intermediate Charcot-Marie-Tooth Neuropathy (<a href="/omim/602378,606482" 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/NBK45014/table/cmt-dib.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cmt-dib.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/602378" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">602378</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DYNAMIN 2; DNM2</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/606482" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">606482</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE B; CMTDIB</td></tr></tbody></table></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 portal104 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>
|