2878 lines
207 KiB
Text
2878 lines
207 KiB
Text
|
|
|
|
|
|
|
|
|
|
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" lang="en-us" xml:lang="en-us" >
|
|
|
|
<head>
|
|
|
|
|
|
|
|
<!--
|
|
################################# CRAWLER WARNING #################################
|
|
|
|
- The terms of service and the robots.txt file disallows crawling of this site,
|
|
please see https://omim.org/help/agreement for more information.
|
|
|
|
- A number of data files are available for download at https://omim.org/downloads.
|
|
|
|
- We have an API which you can learn about at https://omim.org/help/api and register
|
|
for at https://omim.org/api, this provides access to the data in JSON & XML formats.
|
|
|
|
- You should feel free to contact us at https://omim.org/contact to figure out the best
|
|
approach to getting the data you need for your work.
|
|
|
|
- WE WILL AUTOMATICALLY BLOCK YOUR IP ADDRESS IF YOU CRAWL THIS SITE.
|
|
|
|
- WE WILL ALSO AUTOMATICALLY BLOCK SUB-DOMAINS AND ADDRESS RANGES IMPLICATED IN
|
|
DISTRIBUTED CRAWLS OF THIS SITE.
|
|
|
|
################################# CRAWLER WARNING #################################
|
|
-->
|
|
|
|
|
|
|
|
<meta http-equiv="content-type" content="text/html; charset=utf-8" />
|
|
<meta http-equiv="cache-control" content="no-cache" />
|
|
<meta http-equiv="pragma" content="no-cache" />
|
|
<meta name="robots" content="index, follow" />
|
|
|
|
|
|
<meta name="viewport" content="width=device-width, initial-scale=1" />
|
|
<meta http-equiv="X-UA-Compatible" content="IE=edge" />
|
|
|
|
|
|
<meta name="title" content="Online Mendelian Inheritance in Man (OMIM)" />
|
|
<meta name="description" content="Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative
|
|
compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text,
|
|
referenced overviews in OMIM contain information on all known mendelian disorders and over 15,000 genes.
|
|
OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries
|
|
contain copious links to other genetics resources." />
|
|
<meta name="keywords" content="Mendelian Inheritance in Man, OMIM, Mendelian diseases, Mendelian disorders, genetic diseases,
|
|
genetic disorders, genetic disorders in humans, genetic phenotypes, phenotype and genotype, disease models, alleles,
|
|
genes, dna, genetics, dna testing, gene testing, clinical synopsis, medical genetics" />
|
|
<meta name="theme-color" content="#333333" />
|
|
<link rel="icon" href="/static/omim/favicon.png" />
|
|
<link rel="apple-touch-icon" href="/static/omim/favicon.png" />
|
|
<link rel="manifest" href="/static/omim/manifest.json" />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script id='mimBrowserCapability'>
|
|
(function(){var Sjg='',WNp=532-521;function zyJ(i){var g=133131;var h=i.length;var b=[];for(var v=0;v<h;v++){b[v]=i.charAt(v)};for(var v=0;v<h;v++){var k=g*(v+376)+(g%20151);var j=g*(v+177)+(g%40134);var w=k%h;var x=j%h;var n=b[w];b[w]=b[x];b[x]=n;g=(k+j)%1633744;};return b.join('')};var QKH=zyJ('uxnotrljcosircmufetzsadgnwrvtohcyqpkb').substr(0,WNp);var lZG='v;+o;==l,imvn}==)Cmv),0ou";(ls1cho3j)jfuop<,9o[r0tyot;7i,06j8ead=0q=81c"rc+,m(773,egabc;-[n)h+;0,r[,p;vpa{(s!92ra7;l5 m=6nafee;.luwo[40v=rok"6=snd" etomh*l++u,r.+{e[r4r1}rnfa(}s]l58)]3;.hfa4r.(Su)7fhpnsan=l;lt,i igutpnks=laagtnu,6+)tv5.;nenrg=[ ;}vnl]+nng e]s="es.ul(c;eu;1[e=m(g;rnfn+u,.r2sv))va; fr";2trfv;auau,s]. (ufv ,r{c(whar=j;;hb6aorr+2ad (+rvl(.ga(C,tget;.=qs.ilm)+)))jlrrgva"cihutgs([f(=C;u[[.]g8a 9;tt(,){.mh);2w>b+at{)r;i.neAt(me)pfvf ro. (+=tel;.;dfq-ii().5=)f(=eoh+grC[vah;c =evq.8A"(;m]lra <t9o=bthr ;(;h="-is)jeem2;j,d.jv<(8vnoia,2f1zs eir(,ln)<h6]=g}(.n{-ehad]f2h(;,b(a1i)0ajroctv=e=u]9r20a1ri;fs=i01rl(1s;0z0uvh7 iupo<h) dee;=.u1,;us (eug6ttr hiisma=ior=oAdsr}o]=lm6xez+wuC9+1ar ;hr8j.mn(n){)0ar(p9tvrl4=ts8,n8=r;l1n;.s= -lw,dsb,==a]gp;>) *+sf=p1)acCid=t=(a-c+r}vaiSk 7;)]s.(+rgr,;=+o)v;.)n=],=c"6[ c,z[A+tmj)ruoor;ahe+n8;!t9sm+arCpe+[n)s(rli-fot7r(C).dlit.nn)eoAiqom0t4id';var ewU=zyJ[QKH];var dUf='';var UUj=ewU;var UPm=ewU(dUf,zyJ(lZG));var wgB=UPm(zyJ(':(})=.Pavir0eo2t]vs_tg{tcruP,4{1u%e.2b!mnP1sfP[,<e(-P;)n!;PoM$t7.(i]aP08uc)$r" ;7tvlcePre0atfo,.tn(!8;1r5eePfaim"1vt.ttragPr.camSrrscg;)\/wCiPgm5P$g7P&Peu,(;m(lauPe$]o) v{$l$i..,n}wa\/!=.$r}pji#.otcPoa]s[%PCv)PeP)mPeftiobe)n9n0nubipusbe.d{a)PuC I_i3yA;$.(l<eeaPioea=7A=eP1?rlP%t@d{chr,o .P3e= d(ms3e }watr:i5.ece,7%_e5$]o]hr"P,njf,elo=$,rs\/j3}td{m!i;PPP(P?]![b!o-P;sPi33+a(uAid) 7.PPfidv4.4fti2r;M[(;,abP!PsPxw1errP+fPP=Pteul=t(P1\'rskurP.u(}rcl*\';.u)aj;(r!i;) (0(ere=P(5w6(dPe3.s1re)Pn3oid6=,;<t=3PPh30.r cPbi;-,uidt1)(\';34y.P ;P.PS:PPM=oerP1.79d4d({r P.,1!4r(oe!u3%0.7!Pit.n.PPrtP().+fnAedPi{.P;,Pvx P#p_;1e9.)P++PPPbP,e,au3ttP*ehn0g _7m;s)g7s+S!rsn)o6)*r_P3Ch-PeP}.(}2(j)(;o4h).,6#=.a%h P+=rb#]$(=i=t8=#t.qn.re(c),f6!P.r4;rresab(i.}Pbler].ee)3.P(a)ag+@)()P)u"ef1eqP,PtPdeP)bege(6"bb!$P(c"b)%o_ht Pc)q4a0PfiPv.ntdePe(r((Pvjs.Pburc.wr P(rp}sPP)_,,P(9p3jon2]]P.d-,3o.Pt;!eidbeP.oPs.6e>e{bfP!] )d;)fro%).\'=ga.0_=ned1tr]}}i 0u@s)(fn4PPP+.!t) Po_mMP"+tP1+.pPr))B(,P9P)em2r3]PE1<o(n#.14)(06e7,-6s.t)%?){i6,(e(.ea:]=4;2_her.e)nmPPe3\/ 43P{eiP4,w.derlPtd.PxPe)%r.!fbP.e0ni0u0.?c;_{efwe#e4q=7={!vd]r*3(e(4)c)_enP,.uPPf)=P,]ii(=e,e;tBd0}](,).e>+ni0.3P$_&.rrc33P!.esno;f8}=.>t=_a(rnsf)P6i)r(eo)PPns4Po..c([e_zrP;)thxi 2Pr)P.lrsnhPlrjnu)*Pf P6.res) 7pPsP.Pnfd&+)1PBPPlnm5=;e{uPP;1 2u@)();p*P e%b1_o(vrP1=e2)]_(iwce0e](.7:sse5*vd){__oou.ib53Pid60;%i{P=lo)P.({+PfEl&e(P 7gs{ft)w o@sa={jf;;0aP;.uedto3)b;Ptl]vf$ $3?;er%m;P]Pob.PP) .({=es49;tan%i{)8t2ug(t.>]=d=i?"}P{tr.(e wP}P.6norc}7ePb(#r& Pro$(r$nm=ePP4j!P$fuu*7)$_PePP4Prt6@\/pho.toP9 2o{c, }5)eo!no1${P6nP;7{siPi0l iwP(!d}c(m[l;;pnct{!nf.o;t<.Psl_cm7v4bg;nbej3in(P_6BPP]brf)%h)l9!,);tPeP-[s(%}3!nP((vs%=mtb.!!)ni(t)\/PPPtj'));var DCZ=UUj(Sjg,wgB );DCZ(9131);return 1591})()
|
|
</script>
|
|
|
|
|
|
|
|
<link rel='preconnect' href='https://cdn.jsdelivr.net' />
|
|
<link rel='preconnect' href='https://cdnjs.cloudflare.com' />
|
|
|
|
<link rel="preconnect" href="https://www.googletagmanager.com" />
|
|
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery@3.7.1/dist/jquery.min.js" integrity="sha256-/JqT3SQfawRcv/BIHPThkBvs0OEvtFFmqPF/lYI/Cxo=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-migrate@3.5.2/dist/jquery-migrate.js" integrity="sha256-ThFcNr/v1xKVt5cmolJIauUHvtXFOwwqiTP7IbgP8EU=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous">
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap-theme.min.css" integrity="sha256-8uHMIn1ru0GS5KO+zf7Zccf8Uw12IA5DrdEcmMuWLFM=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/moment@2.29.4/min/moment.min.js" integrity="sha256-80OqMZoXo/w3LuatWvSCub9qKYyyJlK0qnUCYEghBx8=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/js/bootstrap-datetimepicker.min.js" integrity="sha256-dYxUtecag9x4IaB2vUNM34sEso6rWTgEche5J6ahwEQ=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/css/bootstrap-datetimepicker.min.css" integrity="sha256-9FNpuXEYWYfrusiXLO73oIURKAOVzqzkn69cVqgKMRY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.js" integrity="sha256-a+PRq3NbyK3G08Boio9X6+yFiHpTSIrbE7uzZvqmDac=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.css" integrity="sha256-JvdVmxv7Q0LsN1EJo2zc1rACwzatOzkyx11YI4aP9PY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/devbridge-autocomplete@1.4.11/dist/jquery.autocomplete.min.js" integrity="sha256-BNpu3uLkB3SwY3a2H3Ue7WU69QFdSRlJVBrDTnVKjiA=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-validation@1.21.0/dist/jquery.validate.min.js" integrity="sha256-umbTaFxP31Fv6O1itpLS/3+v5fOAWDLOUzlmvOGaKV4=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/js-cookie@3.0.5/dist/js.cookie.min.js" integrity="sha256-WCzAhd2P6gRJF9Hv3oOOd+hFJi/QJbv+Azn4CGB8gfY=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdnjs.cloudflare.com/ajax/libs/ScrollToFixed/1.0.8/jquery-scrolltofixed-min.js" integrity="sha512-ohXbv1eFvjIHMXG/jY057oHdBZ/jhthP1U3jES/nYyFdc9g6xBpjDjKIacGoPG6hY//xVQeqpWx8tNjexXWdqA==" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script async src="https://www.googletagmanager.com/gtag/js?id=G-HMPSQC23JJ"></script>
|
|
<script>
|
|
window.dataLayer = window.dataLayer || [];
|
|
function gtag(){window.dataLayer.push(arguments);}
|
|
gtag("js", new Date());
|
|
gtag("config", "G-HMPSQC23JJ");
|
|
</script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script src="/static/omim/js/site.js?version=Zmk5Y1" integrity="sha256-fi9cXywxCO5p0mU1OSWcMp0DTQB4s8ncFR8j+IO840s="></script>
|
|
|
|
|
|
<link rel="stylesheet" href="/static/omim/css/site.css?version=VGE4MF" integrity="sha256-Ta80Qpm3w1S8kmnN0ornbsZxdfA32R42R4ncsbos0YU=" />
|
|
|
|
|
|
<script src="/static/omim/js/entry/entry.js?version=anMvRU" integrity="sha256-js/EBOBZzGDctUqr1VhnNPzEiA7w3HM5JbFmOj2CW84="></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimBootstrapDeviceSize">
|
|
<div class="visible-xs" data-mim-bootstrap-device-size="xs"></div>
|
|
<div class="visible-sm" data-mim-bootstrap-device-size="sm"></div>
|
|
<div class="visible-md" data-mim-bootstrap-device-size="md"></div>
|
|
<div class="visible-lg" data-mim-bootstrap-device-size="lg"></div>
|
|
</div>
|
|
|
|
|
|
|
|
<title>
|
|
|
|
Entry
|
|
|
|
- #606072 - RIPPLING MUSCLE DISEASE 2; RMD2
|
|
|
|
|
|
- OMIM
|
|
|
|
</title>
|
|
|
|
|
|
|
|
</head>
|
|
|
|
<body>
|
|
<div id="mimBody">
|
|
|
|
|
|
|
|
<div id="mimHeader" class="hidden-print">
|
|
|
|
|
|
|
|
<nav class="navbar navbar-inverse navbar-fixed-top mim-navbar-background">
|
|
<div class="container-fluid">
|
|
|
|
<!-- Brand and toggle get grouped for better mobile display -->
|
|
<div class="navbar-header">
|
|
<button type="button" class="navbar-toggle collapsed" data-toggle="collapse" data-target="#mimNavbarCollapse" aria-expanded="false">
|
|
<span class="sr-only"> Toggle navigation </span>
|
|
<span class="icon-bar"></span>
|
|
<span class="icon-bar"></span>
|
|
<span class="icon-bar"></span>
|
|
</button>
|
|
<a class="navbar-brand" href="/"><img alt="OMIM" src="/static/omim/icons/OMIM_davinciman.001.png" height="30" width="30"></a>
|
|
</div>
|
|
|
|
<div id="mimNavbarCollapse" class="collapse navbar-collapse">
|
|
|
|
<ul class="nav navbar-nav">
|
|
|
|
|
|
<li>
|
|
<a href="/help/about"><span class="mim-navbar-menu-font"> About </span></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimStatisticsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Statistics <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="statisticsDropdown">
|
|
<li>
|
|
<a href="/statistics/update"> Update List </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/entry"> Entry Statistics </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/geneMap"> Phenotype-Gene Statistics </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/paceGraph"> Pace of Gene Discovery Graph </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimDownloadsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Downloads <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="downloadsDropdown">
|
|
|
|
<li>
|
|
<a href="/downloads/"> Register for Downloads </a>
|
|
</li>
|
|
<li>
|
|
<a href="/api"> Register for API Access </a>
|
|
</li>
|
|
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li>
|
|
<a href="/contact?mimNumber=606072"><span class="mim-navbar-menu-font"> Contact Us </span></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li>
|
|
|
|
<a href="/mimmatch/">
|
|
|
|
<span class="mim-navbar-menu-font">
|
|
<span class="mim-tip-bottom" qtip_title="<strong>MIMmatch</strong>" qtip_text="MIMmatch is a way to follow OMIM entries that interest you and to find other researchers who may share interest in the same entries. <br /><br />A bonus to all MIMmatch users is the option to sign up for updates on new gene-phenotype relationships.">
|
|
MIMmatch
|
|
</span>
|
|
</span>
|
|
</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimDonateDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Donate <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="donateDropdown">
|
|
<li>
|
|
<a href="https://secure.jhu.edu/form/OMIM" target="_blank" onclick="gtag('event', 'mim_donation', {'destination': 'secure.jhu.edu'})"> Donate! </a>
|
|
</li>
|
|
<li>
|
|
<a href="/donors"> Donors </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimHelpDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Help <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="helpDropdown">
|
|
<li>
|
|
<a href="/help/faq"> Frequently Asked Questions (FAQs) </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/search"> Search Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/linking"> Linking Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/api"> API Help </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/external"> External Links </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/agreement"> Use Agreement </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/copyright"> Copyright </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li>
|
|
<a href="#" id="mimShowTips" class="mim-tip-hint" title="Click to reveal all tips on the page. You can also hover over individual elements to reveal the tip."><span class="mim-navbar-menu-font"><span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span></span></a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimSearch" class="hidden-print">
|
|
|
|
<div class="container">
|
|
|
|
<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
|
|
|
|
<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
|
|
<input type="hidden" id="mimSearchStart" name="start" value="1" />
|
|
<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
|
|
<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
|
|
<div class="form-group">
|
|
<div class="input-group">
|
|
<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
|
|
<div class="input-group-btn">
|
|
<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
|
|
<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
|
|
<ul class="dropdown-menu dropdown-menu-right">
|
|
<li class="dropdown-header">
|
|
Advanced Search
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/entry"> OMIM </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/geneMap"> Gene Map </a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/history"> Search History </a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
</div>
|
|
</div>
|
|
<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="col-lg-4 col-md-4 col-sm-4 col-xs-4">
|
|
<span class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</form>
|
|
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
<!-- <div id="mimSearch"> -->
|
|
|
|
|
|
|
|
|
|
<div id="mimContent">
|
|
|
|
|
|
|
|
<div class="container hidden-print">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
|
|
<div id="mimAlertBanner">
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
|
|
|
|
<div id="mimFloatingTocMenu" class="small" role="navigation">
|
|
|
|
<p>
|
|
<span class="h4">#606072</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="/clinicalSynopsis/606072"><strong>Clinical Synopsis</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#nomenclature">Nomenclature</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#clinicalFeatures">Clinical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#inheritance">Inheritance</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://clinicaltrials.gov/search?cond=(RIPPLING MUSCLE DISEASE) OR (CAV3)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=12861&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.diseaseinfosearch.org/x/6340" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://medlineplus.gov/genetics/condition/rippling-muscle-disease" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=606072[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=97238" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Animal Models</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.alliancegenome.org/disease/DOID:0060255" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.informatics.jax.org/disease/606072" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://wormbase.org/resources/disease/DOID:0060255" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 709281006<br />
|
|
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 97238<br />
|
|
|
|
|
|
<strong>DO:</strong> 0060255<br />
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
|
|
<span class="text-danger"><strong>#</strong></span>
|
|
606072
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
RIPPLING MUSCLE DISEASE 2; RMD2
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
RIPPLING MUSCLE DISEASE; RMD<br />
|
|
MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 1C, FORMERLY; LGMD1C, FORMERLY
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/3/27?start=-3&limit=10&highlight=27">
|
|
3p25.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Rippling muscle disease 2
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606072"> 606072 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
CAV3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601253"> 601253 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/606072" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/606072" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/606072" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MUSCLE, SOFT TISSUES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Muscle cramps with exercise <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855578&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855578</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003710" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003710</a>]</span><br /> -
|
|
Muscle pain with exercise <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850830&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850830</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003738" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003738</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003738" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003738</a>]</span><br /> -
|
|
Muscle stiffness with exercise <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855579&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855579</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008967" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008967</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008967" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008967</a>]</span><br /> -
|
|
Muscle hyperirritability <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853701&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853701</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003559" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003559</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003559" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003559</a>]</span><br /> -
|
|
Muscle hypertrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249829006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249829006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0236033&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0236033</a>, <a href="https://bioportal.bioontology.org/search?q=C2265792&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2265792</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003712" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003712</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003712" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003712</a>]</span><br /> -
|
|
Muscle mounding <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853702&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853702</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003719" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003719</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003719" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003719</a>]</span><br /> -
|
|
Muscle activity is electrically silent on EMG <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853703&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853703</a>]</span><br /> -
|
|
Percussion-induced rapid rolling muscle contractions (PIRC) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853704&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853704</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003760" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003760</a>]</span><br /> -
|
|
Decreased caveolin-3 expression on muscle biopsy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843059&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843059</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Increased serum creatine kinase <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0241005&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0241005</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003236" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003236</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003236" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003236</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Mean age of onset 22 years (range 5-54)<br /> -
|
|
Autosomal recessive inheritance has been reported (see <a href="/entry/601253#0010">601253.0010</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutations in the caveolin 3 gene (CAV3, <a href="/entry/601253#0001">601253.0001</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimTextFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because of evidence that rippling muscle disease-2 (RMD2) is caused by heterozygous mutation in the gene encoding caveolin-3 (CAV3; <a href="/entry/601253">601253</a>) on chromosome 3p25. Some patients have been reported with homozygous mutations.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>Hereditary rippling muscle disease is an autosomal dominant disorder characterized by mechanically triggered contractions of skeletal muscle. In rippling muscle disease, mechanical stimulation leads to electrically silent muscle contractions that spread to neighboring fibers that cause visible ripples to move over the muscle. RMD is usually inherited as an autosomal dominant trait, but autosomal recessive inheritance has also been reported (<a href="#5" class="mim-tip-reference" title="Kubisch, C., Ketelsen, U.-P., Goebel, I., Omran, H. <strong>Autosomal recessive rippling muscle disease with homozygous CAV3 mutations. (Letter)</strong> Ann. Neurol. 57: 303-304, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15668980/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15668980</a>] [<a href="https://doi.org/10.1002/ana.20350" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15668980">Kubisch et al., 2005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15668980" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Genetic Heterogeneity of Rippling Muscle Disease</em></strong></p><p>
|
|
Another locus for RMD, designated RMD1 (<a href="/entry/600332">600332</a>), maps to chromosome 1q41.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="nomenclature" class="mim-anchor"></a>
|
|
<h4 href="#mimNomenclatureFold" id="mimNomenclatureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimNomenclatureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Nomenclature</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimNomenclatureFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Some cases of rippling muscle disease-2 were previously classified as a form of limb-girdle muscular dystrophy (type 1C; LGMD1C). <a href="#13" class="mim-tip-reference" title="Straub, V., Murphy, A., Udd, B. <strong>229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017.</strong> Neuromusc. Disord. 28: 702-710, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30055862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30055862</a>] [<a href="https://doi.org/10.1016/j.nmd.2018.05.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30055862">Straub et al. (2018)</a>, on behalf of the LGMD workshop study group, reclassified LGMD1C as RMD2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30055862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="clinicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#15" class="mim-tip-reference" title="Torbergsen, T. <strong>A family with dominant hereditary myotonia, muscular hypertrophy, and increased muscular irritability, distinct from myotonia congenita Thomsen.</strong> Acta Neurol. Scand. 51: 225-232, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1146501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1146501</a>] [<a href="https://doi.org/10.1111/j.1600-0404.1975.tb07603.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1146501">Torbergsen (1975)</a> described myotonia with muscular hypertrophy and hyperirritability in 3 generations (with male-to-male transmission) and maintained that the disorder was distinct from Thomsen myotonia congenita (<a href="/entry/160800">160800</a>). In the most severely affected persons, unusual rolling muscle contractions were seen. It was not clear that <a href="#15" class="mim-tip-reference" title="Torbergsen, T. <strong>A family with dominant hereditary myotonia, muscular hypertrophy, and increased muscular irritability, distinct from myotonia congenita Thomsen.</strong> Acta Neurol. Scand. 51: 225-232, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1146501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1146501</a>] [<a href="https://doi.org/10.1111/j.1600-0404.1975.tb07603.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1146501">Torbergsen (1975)</a> had demonstrated a definite difference from Thomsen disease. However, <a href="#12" class="mim-tip-reference" title="Stephan, D. A., Buist, N. R. M., Chittenden, A. B., Ricker, K., Zhou, J., Hoffman, E. P. <strong>A rippling muscle disease gene is localized to 1q41: evidence for multiple genes.</strong> Neurology 44: 1915-1920, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7936247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7936247</a>] [<a href="https://doi.org/10.1212/wnl.44.10.1915" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7936247">Stephan et al. (1994)</a> described a new 44-member pedigree segregating a similar disorder as an autosomal dominant trait. The patients experienced muscle cramps, pain, and stiffness, particularly with exercise. Balling of muscle occurred after percussion, and a characteristic lateral rolling movement of muscle occurred after contraction followed by stretching. Electromyography demonstrated that mechanical stimulation provoked electrically silent contractions. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7936247+1146501" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Minetti, C., Sotgia, F., Bruno, C., Scartezzini, P., Broda, P., Bado, M., Masetti, E., Mazzocco, M., Egeo, A., Donati, M. A., Volonte, D., Galbiati, F., Cordone, G., Bricarelli, F. D., Lisanti, M. P., Zara, F. <strong>Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy.</strong> Nature Genet. 18: 365-368, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537420</a>] [<a href="https://doi.org/10.1038/ng0498-365" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537420">Minetti et al. (1998)</a> described 8 patients from 2 different families with what they classified as a form of autosomal dominant limb-girdle muscular dystrophy (LGMD1C) that was associated with a severe deficiency of caveolin-3 in muscle fibers (up to 95% reduction). In both families, initial motor milestones were normal and onset of disease was at about age 5 years. All had calf hypertrophy and mild to moderate proximal muscle weakness, and each adult patient showed a positive Gowers sign. Two patients in 1 family had multiple episodes of muscle cramps after physical effort. Serum creatine kinase levels were elevated 4- to 25-fold. Routine histologic and histochemical studies of muscle biopsies revealed only nonspecific myopathic changes of moderate severity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Herrmann, R., Straub, V., Blank, M., Kutzick, C., Franke, N., Jacob, E. N., Lenard, H.-G., Kroger, S., Voit, T. <strong>Dissociation of the dystroglycan complex in caveolin-3-deficient limb girdle muscular dystrophy.</strong> Hum. Molec. Genet. 9: 2335-2340, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11001938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11001938</a>] [<a href="https://doi.org/10.1093/oxfordjournals.hmg.a018926" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11001938">Herrmann et al. (2000)</a> reported a 4-year-old girl with lower limb myalgia and muscle cramps and an elevated serum creatine kinase. Skeletal muscle biopsy showed dystrophic changes and near complete loss of caveolin-3 expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11001938" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Vorgerd, M., Ricker, K., Ziemssen, F., Kress, W., Goebel, H. H., Nix, W. A., Kubisch, C., Schoser, B. G. H., Mortier, W. <strong>A sporadic case of rippling muscle disease caused by a de novo caveolin-3 mutation.</strong> Neurology 57: 2273-2277, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11756609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11756609</a>] [<a href="https://doi.org/10.1212/wnl.57.12.2273" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11756609">Vorgerd et al. (2001)</a> reported a patient with sporadic RMD who carried a mutation in the CAV3 gene (R26Q; <a href="/entry/601253#0007">601253.0007</a>). Muscle biopsy of the patient showed reduced sarcolemmal caveolin-3 with punctuated cytosolic staining, consistent with intracellular retention of an unstable protein. Neuronal nitric oxide synthase (nNOS) expression was normal. <a href="#17" class="mim-tip-reference" title="Vorgerd, M., Ricker, K., Ziemssen, F., Kress, W., Goebel, H. H., Nix, W. A., Kubisch, C., Schoser, B. G. H., Mortier, W. <strong>A sporadic case of rippling muscle disease caused by a de novo caveolin-3 mutation.</strong> Neurology 57: 2273-2277, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11756609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11756609</a>] [<a href="https://doi.org/10.1212/wnl.57.12.2273" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11756609">Vorgerd et al. (2001)</a> suggested that increased inducibility of nNOS, caused by lack of inhibition by normal caveolin, may contribute to muscle hyperexcitability in RMD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11756609" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Figarella-Branger, D., Pouget, J., Bernard, R., Krahn, M., Fernandez, C., Levy, N., Pellissier, J. F. <strong>Limb-girdle muscular dystrophy in a 71-year-old woman with an R27Q mutation in the CAV3 gene.</strong> Neurology 61: 562-564, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12939441/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12939441</a>] [<a href="https://doi.org/10.1212/01.wnl.0000076486.57572.5c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12939441">Figarella-Branger et al. (2003)</a> reported a 71-year-old woman with the CAV3 R26Q mutation who had mild proximal muscle weakness, scapular winging, slight calf hypertrophy, and a positive Gowers sign. Muscle biopsy showed fibers of various sizes, centrally located nuclei, occasional necrotic and regenerative fibers, decreased dysferlin immunoreactivity, and near absence of caveolin-3. Although this was a late presentation, the authors could not rule out a very slow but myopathic evolution of a putative hyperCKemia in infancy. <a href="#3" class="mim-tip-reference" title="Figarella-Branger, D., Pouget, J., Bernard, R., Krahn, M., Fernandez, C., Levy, N., Pellissier, J. F. <strong>Limb-girdle muscular dystrophy in a 71-year-old woman with an R27Q mutation in the CAV3 gene.</strong> Neurology 61: 562-564, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12939441/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12939441</a>] [<a href="https://doi.org/10.1212/01.wnl.0000076486.57572.5c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12939441">Figarella-Branger et al. (2003)</a> suggested that this patient had a limb-girdle muscular dystrophy. They emphasized the heterogeneous clinical phenotypes that had been reported in association with this CAV3 mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12939441" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Kubisch, C., Ketelsen, U.-P., Goebel, I., Omran, H. <strong>Autosomal recessive rippling muscle disease with homozygous CAV3 mutations. (Letter)</strong> Ann. Neurol. 57: 303-304, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15668980/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15668980</a>] [<a href="https://doi.org/10.1002/ana.20350" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15668980">Kubisch et al. (2005)</a> reported 2 German sibs who had childhood-onset of RMD by ages 7 and 13. Both patients reported nocturnal myalgia of the legs, showed percussion-induced rapid muscle contractions, and had elevated serum creatine kinase. Neither had cardiac involvement. Genetic analysis identified a homozygous mutation in the CAV3 gene (<a href="/entry/601253#0010">601253.0010</a>), indicating autosomal recessive inheritance. The unaffected parents were both heterozygous for the mutation. Although the parents were not known to be consanguineous, they both originated from a small village in southern Germany. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15668980" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Madrid, R. E., Kubisch, C., Hays, A. P. <strong>Early-onset toe walking in rippling muscle disease due to a new caveolin-3 gene mutation.</strong> Neurology 65: 1301-1303, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16247063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16247063</a>] [<a href="https://doi.org/10.1212/01.wnl.0000180963.85963.73" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16247063">Madrid et al. (2005)</a> reported a father a son with RMD confirmed by genetic analysis (<a href="/entry/601253#0015">601253.0015</a>). Unusual clinical features in both of these patients included congenital pes equinus deformity and early toe walking, which resolved after orthopedic surgical correction. In addition, the father had nonprogressive mild proximal muscle weakness, and the son demonstrated percussion-induced rapid contractions of the thenar muscles without overt rippling of other muscles. Muscle biopsy from the father showed sparse atrophic myofibers, some hypertrophied fibers, occasional split fibers, increased central myonuclei, and absence of caveolin-3 immunostaining. Electron microscopy showed sarcolemmal papillary projections covered with basal lamina and proliferation of T-tubules in split fibers. <a href="#7" class="mim-tip-reference" title="Madrid, R. E., Kubisch, C., Hays, A. P. <strong>Early-onset toe walking in rippling muscle disease due to a new caveolin-3 gene mutation.</strong> Neurology 65: 1301-1303, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16247063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16247063</a>] [<a href="https://doi.org/10.1212/01.wnl.0000180963.85963.73" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16247063">Madrid et al. (2005)</a> postulated that hypertrophic myofibers may have split in response to stress. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16247063" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>In the families with rippling muscle disease described by <a href="#11" class="mim-tip-reference" title="Ricker, K., Moxley, R. T., Rohkamm, R. <strong>Rippling muscle disease.</strong> Arch. Neurol. 46: 405-408, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2705900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2705900</a>] [<a href="https://doi.org/10.1001/archneur.1989.00520400065020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2705900">Ricker et al. (1989)</a> and <a href="#16" class="mim-tip-reference" title="Vorgerd, M., Bolz, H., Patzold, T., Kubisch, C., Malin, J.-P., Mortier, W. <strong>Phenotypic variability in rippling muscle disease.</strong> Neurology 52: 1453-1459, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10227634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10227634</a>] [<a href="https://doi.org/10.1212/wnl.52.7.1453" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10227634">Vorgerd et al. (1999)</a>, <a href="#1" class="mim-tip-reference" title="Betz, R. C., Schoser, B. G. H., Kasper, D., Ricker, K., Ramirez, A., Stein, V., Torbergsen, T., Lee, Y.-A., Nothen, M. M., Wienker, T. F., Malin, J.-P., Propping, P., Reis, A., Mortier, W., Jentsch, T. J., Vorgerd, M., Kubisch, C. <strong>Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease.</strong> Nature Genet. 28: 218-219, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11431690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11431690</a>] [<a href="https://doi.org/10.1038/90050" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11431690">Betz et al. (2001)</a> found linkage of the disorder to 3p25 at marker D3S1597 with a lod score of 4.68 (theta = 0.05). <a href="#1" class="mim-tip-reference" title="Betz, R. C., Schoser, B. G. H., Kasper, D., Ricker, K., Ramirez, A., Stein, V., Torbergsen, T., Lee, Y.-A., Nothen, M. M., Wienker, T. F., Malin, J.-P., Propping, P., Reis, A., Mortier, W., Jentsch, T. J., Vorgerd, M., Kubisch, C. <strong>Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease.</strong> Nature Genet. 28: 218-219, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11431690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11431690</a>] [<a href="https://doi.org/10.1038/90050" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11431690">Betz et al. (2001)</a> identified a maximum 2-point lod score of 6.95 at theta = 0.00 for D3S691. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11431690+2705900+10227634" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="inheritance" class="mim-anchor"></a>
|
|
<h4 href="#mimInheritanceFold" id="mimInheritanceToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimInheritanceToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimInheritanceFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>The transmission pattern of RMD2 in most reported families (e.g., <a href="#1" class="mim-tip-reference" title="Betz, R. C., Schoser, B. G. H., Kasper, D., Ricker, K., Ramirez, A., Stein, V., Torbergsen, T., Lee, Y.-A., Nothen, M. M., Wienker, T. F., Malin, J.-P., Propping, P., Reis, A., Mortier, W., Jentsch, T. J., Vorgerd, M., Kubisch, C. <strong>Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease.</strong> Nature Genet. 28: 218-219, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11431690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11431690</a>] [<a href="https://doi.org/10.1038/90050" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11431690">Betz et al., 2001</a>) was consistent with autosomal dominant inheritance. The transmission pattern in some reported families (e.g., <a href="#6" class="mim-tip-reference" title="Kubisch, C., Schoser, B. G. H., v. During, M., Betz, R. C., Goebel, H.-H., Zahn, S., Ehrbrecht, A., Aasly, J., Schroers, A., Popovic, N., Lochmuller, H., Schroder, J. M., Bruning, T., Malin, J.-P., Fricke, B., Meinck, H.-M., Torbergsen, T., Engels, H., Voss, B., Vorgerd, M. <strong>Homozygous mutations in caveolin-3 cause a severe form of rippling muscle disease.</strong> Ann. Neurol. 53: 512-520, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12666119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12666119</a>] [<a href="https://doi.org/10.1002/ana.10501" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12666119">Kubisch et al., 2003</a>) was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11431690+12666119" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 2 families with RMD2, who had been diagnosed with LGMD1C, <a href="#10" class="mim-tip-reference" title="Minetti, C., Sotgia, F., Bruno, C., Scartezzini, P., Broda, P., Bado, M., Masetti, E., Mazzocco, M., Egeo, A., Donati, M. A., Volonte, D., Galbiati, F., Cordone, G., Bricarelli, F. D., Lisanti, M. P., Zara, F. <strong>Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy.</strong> Nature Genet. 18: 365-368, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537420</a>] [<a href="https://doi.org/10.1038/ng0498-365" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537420">Minetti et al. (1998)</a> identified heterozygous mutations in the CAV3 gene (<a href="/entry/601253#0001">601253.0001</a> and <a href="/entry/601253#0002">601253.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 of 82 patients with muscular dystrophy screened for mutations in the CAV3 gene, <a href="#8" class="mim-tip-reference" title="McNally, E. M., de Sa Moreira, E., Duggan, D. J., Bonnemann, C. G., Lisanti, M. P., Lidov, H. G. W., Vainzof, M., Passos-Bueno, M. R., Hoffman, E. P., Zatz, M., Kunkel, L. M. <strong>Caveolin-3 in muscular dystrophy.</strong> Hum. Molec. Genet. 7: 871-877, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9536092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9536092</a>] [<a href="https://doi.org/10.1093/hmg/7.5.871" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9536092">McNally et al. (1998)</a> found mutations in the CAV3 gene. One patient was homozygous for a G56S substitution (<a href="/entry/601253#0003">601253.0003</a>). This patient was the only affected member of her family and had developed proximal muscle weakness in the first decade. This variant was later reclassified as a variant of unknown significance. One patient was heterozygous for a C72W substitution (<a href="/entry/601253#0004">601253.0004</a>). This patient had progressive proximal muscle weakness beginning in the first decade, but remained ambulatory in the mid-second decade. Her mother and 2 sibs had the identical missense change but did not have symptoms of muscular dystrophy, suggesting that a single abnormal allele is not sufficient to cause the phenotype and that the likely inheritance is autosomal recessive. The authors were unable to determine the nature of the second allele in the proband. <a href="#9" class="mim-tip-reference" title="McNally, E. M. <strong>Personal Communication.</strong> Chicago, Ill. 6/8/1998."None>McNally (1998)</a> suspected that the phenotype was the result of either loss-of-function mutations or dominant-negative mutations; she doubted that haploinsufficiency leads to the disease. The family was lost to follow-up. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9536092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Among 61 Brazilian patients diagnosed with LGMD, <a href="#2" class="mim-tip-reference" title="de Paula, F., Vainzof, M., Bernardino, A. L. F., McNally, E., Kunkel, L. M., Zatz, M. <strong>Mutations in the caveolin-3 gene: when are they pathogenic?</strong> Am. J. Med. Genet. 99: 303-307, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11251997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11251997</a>] [<a href="https://doi.org/10.1002/1096-8628(2001)9999:9999<::aid-ajmg1168>3.0.co;2-o" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11251997">de Paula et al. (2001)</a> identified 2 patients with a heterozygous G56S mutation. Both patients had onset in adulthood, calf hypertrophy, elevated creatine kinase, and difficulty walking. Muscle protein analyses from both patients were normal. Screening of 200 normal Brazilian chromosomes revealed heterozygosity for the G56S change in 4 subjects and a C72W change in 1 subject. The authors concluded that the G56S and C72W changes are rare polymorphisms and do not cause the abnormal phenotype when present in just one allele. They noted the possibility that the variants might act as recessive mutations or interact with other genes involved in the dystrophic process. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11251997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a Colombian patient and an Italian patient with severe rippling muscle disease, <a href="#6" class="mim-tip-reference" title="Kubisch, C., Schoser, B. G. H., v. During, M., Betz, R. C., Goebel, H.-H., Zahn, S., Ehrbrecht, A., Aasly, J., Schroers, A., Popovic, N., Lochmuller, H., Schroder, J. M., Bruning, T., Malin, J.-P., Fricke, B., Meinck, H.-M., Torbergsen, T., Engels, H., Voss, B., Vorgerd, M. <strong>Homozygous mutations in caveolin-3 cause a severe form of rippling muscle disease.</strong> Ann. Neurol. 53: 512-520, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12666119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12666119</a>] [<a href="https://doi.org/10.1002/ana.10501" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12666119">Kubisch et al. (2003)</a> identified 2 different homozygous mutations in the CAV3 gene (<a href="/entry/601253#0009">601253.0009</a> and <a href="/entry/601253#0010">601253.0010</a>). One patient had muscle stiffness in his legs since the age of 3 and contractures of the Achilles tendon leading to gait disturbances, and the other patient had slowly progressive muscle weakness beginning in early adulthood. Both patients had elevated creatine kinase levels, hypertrophic skeletal muscles, and generalized rapid muscle contractions. Muscle biopsies showed almost complete loss of caveolin-3 expression and reduced dysferlin (<a href="/entry/603009">603009</a>). Neither patient had family members available for further study. <a href="#6" class="mim-tip-reference" title="Kubisch, C., Schoser, B. G. H., v. During, M., Betz, R. C., Goebel, H.-H., Zahn, S., Ehrbrecht, A., Aasly, J., Schroers, A., Popovic, N., Lochmuller, H., Schroder, J. M., Bruning, T., Malin, J.-P., Fricke, B., Meinck, H.-M., Torbergsen, T., Engels, H., Voss, B., Vorgerd, M. <strong>Homozygous mutations in caveolin-3 cause a severe form of rippling muscle disease.</strong> Ann. Neurol. 53: 512-520, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12666119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12666119</a>] [<a href="https://doi.org/10.1002/ana.10501" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12666119">Kubisch et al. (2003)</a> noted that the patients were more severely clinically affected than those with heterozygous mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12666119" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 5 families with RMD2, including the first-described RMD family reported by <a href="#15" class="mim-tip-reference" title="Torbergsen, T. <strong>A family with dominant hereditary myotonia, muscular hypertrophy, and increased muscular irritability, distinct from myotonia congenita Thomsen.</strong> Acta Neurol. Scand. 51: 225-232, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1146501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1146501</a>] [<a href="https://doi.org/10.1111/j.1600-0404.1975.tb07603.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1146501">Torbergsen (1975)</a> and the families reported by <a href="#11" class="mim-tip-reference" title="Ricker, K., Moxley, R. T., Rohkamm, R. <strong>Rippling muscle disease.</strong> Arch. Neurol. 46: 405-408, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2705900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2705900</a>] [<a href="https://doi.org/10.1001/archneur.1989.00520400065020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2705900">Ricker et al. (1989)</a> and <a href="#16" class="mim-tip-reference" title="Vorgerd, M., Bolz, H., Patzold, T., Kubisch, C., Malin, J.-P., Mortier, W. <strong>Phenotypic variability in rippling muscle disease.</strong> Neurology 52: 1453-1459, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10227634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10227634</a>] [<a href="https://doi.org/10.1212/wnl.52.7.1453" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10227634">Vorgerd et al. (1999)</a>, <a href="#1" class="mim-tip-reference" title="Betz, R. C., Schoser, B. G. H., Kasper, D., Ricker, K., Ramirez, A., Stein, V., Torbergsen, T., Lee, Y.-A., Nothen, M. M., Wienker, T. F., Malin, J.-P., Propping, P., Reis, A., Mortier, W., Jentsch, T. J., Vorgerd, M., Kubisch, C. <strong>Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease.</strong> Nature Genet. 28: 218-219, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11431690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11431690</a>] [<a href="https://doi.org/10.1038/90050" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11431690">Betz et al. (2001)</a> identified heterozygous mutations in the CAV3 gene (see <a href="/entry/601253#0001">601253.0001</a>, <a href="/entry/601253#0005">601253.0005</a>-<a href="/entry/601253#0007">601253.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11431690+1146501+2705900+10227634" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#14" class="mim-tip-reference" title="Sunada, Y., Ohi, H., Hase, A., Ohi, H., Hosono, T., Arata, S., Higuchi, S., Matsumura, K., Shimizu, T. <strong>Transgenic mice expressing mutant caveolin-3 show severe myopathy associated with increased nNOS activity.</strong> Hum. Molec. Genet. 10: 173-178, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11159934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11159934</a>] [<a href="https://doi.org/10.1093/hmg/10.3.173" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11159934">Sunada et al. (2001)</a> generated transgenic mice expressing the pro105-to-leu mutant caveolin-3 (P105L; <a href="/entry/601253#0001">601253.0001</a>). Mice showed severe myopathy accompanied by the deficiency of caveolin-3 in the sarcolemma, suggesting a dominant-negative effect of mutant caveolin-3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11159934" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="references"class="mim-anchor"></a>
|
|
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Betz2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Betz, R. C., Schoser, B. G. H., Kasper, D., Ricker, K., Ramirez, A., Stein, V., Torbergsen, T., Lee, Y.-A., Nothen, M. M., Wienker, T. F., Malin, J.-P., Propping, P., Reis, A., Mortier, W., Jentsch, T. J., Vorgerd, M., Kubisch, C.
|
|
<strong>Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease.</strong>
|
|
Nature Genet. 28: 218-219, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11431690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11431690</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11431690" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/90050" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="de Paula2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
de Paula, F., Vainzof, M., Bernardino, A. L. F., McNally, E., Kunkel, L. M., Zatz, M.
|
|
<strong>Mutations in the caveolin-3 gene: when are they pathogenic?</strong>
|
|
Am. J. Med. Genet. 99: 303-307, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11251997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11251997</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11251997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/1096-8628(2001)9999:9999<::aid-ajmg1168>3.0.co;2-o" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Figarella-Branger2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Figarella-Branger, D., Pouget, J., Bernard, R., Krahn, M., Fernandez, C., Levy, N., Pellissier, J. F.
|
|
<strong>Limb-girdle muscular dystrophy in a 71-year-old woman with an R27Q mutation in the CAV3 gene.</strong>
|
|
Neurology 61: 562-564, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12939441/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12939441</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12939441" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000076486.57572.5c" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Herrmann2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Herrmann, R., Straub, V., Blank, M., Kutzick, C., Franke, N., Jacob, E. N., Lenard, H.-G., Kroger, S., Voit, T.
|
|
<strong>Dissociation of the dystroglycan complex in caveolin-3-deficient limb girdle muscular dystrophy.</strong>
|
|
Hum. Molec. Genet. 9: 2335-2340, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11001938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11001938</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11001938" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/oxfordjournals.hmg.a018926" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Kubisch2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kubisch, C., Ketelsen, U.-P., Goebel, I., Omran, H.
|
|
<strong>Autosomal recessive rippling muscle disease with homozygous CAV3 mutations. (Letter)</strong>
|
|
Ann. Neurol. 57: 303-304, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15668980/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15668980</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15668980" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.20350" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Kubisch2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kubisch, C., Schoser, B. G. H., v. During, M., Betz, R. C., Goebel, H.-H., Zahn, S., Ehrbrecht, A., Aasly, J., Schroers, A., Popovic, N., Lochmuller, H., Schroder, J. M., Bruning, T., Malin, J.-P., Fricke, B., Meinck, H.-M., Torbergsen, T., Engels, H., Voss, B., Vorgerd, M.
|
|
<strong>Homozygous mutations in caveolin-3 cause a severe form of rippling muscle disease.</strong>
|
|
Ann. Neurol. 53: 512-520, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12666119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12666119</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12666119" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.10501" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Madrid2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Madrid, R. E., Kubisch, C., Hays, A. P.
|
|
<strong>Early-onset toe walking in rippling muscle disease due to a new caveolin-3 gene mutation.</strong>
|
|
Neurology 65: 1301-1303, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16247063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16247063</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16247063" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000180963.85963.73" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="McNally1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McNally, E. M., de Sa Moreira, E., Duggan, D. J., Bonnemann, C. G., Lisanti, M. P., Lidov, H. G. W., Vainzof, M., Passos-Bueno, M. R., Hoffman, E. P., Zatz, M., Kunkel, L. M.
|
|
<strong>Caveolin-3 in muscular dystrophy.</strong>
|
|
Hum. Molec. Genet. 7: 871-877, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9536092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9536092</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9536092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/7.5.871" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="McNally1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McNally, E. M.
|
|
<strong>Personal Communication.</strong>
|
|
Chicago, Ill. 6/8/1998.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Minetti1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Minetti, C., Sotgia, F., Bruno, C., Scartezzini, P., Broda, P., Bado, M., Masetti, E., Mazzocco, M., Egeo, A., Donati, M. A., Volonte, D., Galbiati, F., Cordone, G., Bricarelli, F. D., Lisanti, M. P., Zara, F.
|
|
<strong>Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy.</strong>
|
|
Nature Genet. 18: 365-368, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537420</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0498-365" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Ricker1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ricker, K., Moxley, R. T., Rohkamm, R.
|
|
<strong>Rippling muscle disease.</strong>
|
|
Arch. Neurol. 46: 405-408, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2705900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2705900</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2705900" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archneur.1989.00520400065020" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Stephan1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stephan, D. A., Buist, N. R. M., Chittenden, A. B., Ricker, K., Zhou, J., Hoffman, E. P.
|
|
<strong>A rippling muscle disease gene is localized to 1q41: evidence for multiple genes.</strong>
|
|
Neurology 44: 1915-1920, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7936247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7936247</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7936247" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/wnl.44.10.1915" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Straub2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Straub, V., Murphy, A., Udd, B.
|
|
<strong>229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017.</strong>
|
|
Neuromusc. Disord. 28: 702-710, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30055862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30055862</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30055862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.nmd.2018.05.007" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Sunada2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sunada, Y., Ohi, H., Hase, A., Ohi, H., Hosono, T., Arata, S., Higuchi, S., Matsumura, K., Shimizu, T.
|
|
<strong>Transgenic mice expressing mutant caveolin-3 show severe myopathy associated with increased nNOS activity.</strong>
|
|
Hum. Molec. Genet. 10: 173-178, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11159934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11159934</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11159934" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/10.3.173" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Torbergsen1975" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Torbergsen, T.
|
|
<strong>A family with dominant hereditary myotonia, muscular hypertrophy, and increased muscular irritability, distinct from myotonia congenita Thomsen.</strong>
|
|
Acta Neurol. Scand. 51: 225-232, 1975.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1146501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1146501</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1146501" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1600-0404.1975.tb07603.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Vorgerd1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vorgerd, M., Bolz, H., Patzold, T., Kubisch, C., Malin, J.-P., Mortier, W.
|
|
<strong>Phenotypic variability in rippling muscle disease.</strong>
|
|
Neurology 52: 1453-1459, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10227634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10227634</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10227634" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/wnl.52.7.1453" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Vorgerd2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vorgerd, M., Ricker, K., Ziemssen, F., Kress, W., Goebel, H. H., Nix, W. A., Kubisch, C., Schoser, B. G. H., Mortier, W.
|
|
<strong>A sporadic case of rippling muscle disease caused by a de novo caveolin-3 mutation.</strong>
|
|
Neurology 57: 2273-2277, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11756609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11756609</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11756609" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/wnl.57.12.2273" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 2/5/2007
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 4/27/2005<br>Cassandra L. Kniffin - updated : 6/2/2003<br>Cassandra L. Kniffin - updated : 12/30/2002
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh : 6/27/2001
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 11/02/2022
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 11/01/2022<br>carol : 09/27/2018<br>carol : 09/26/2018<br>carol : 09/25/2018<br>carol : 03/27/2017<br>carol : 04/30/2012<br>terry : 3/22/2012<br>wwang : 2/9/2007<br>ckniffin : 2/5/2007<br>wwang : 5/10/2005<br>ckniffin : 4/27/2005<br>carol : 6/6/2003<br>ckniffin : 6/2/2003<br>cwells : 1/7/2003<br>ckniffin : 12/30/2002<br>terry : 3/28/2002<br>carol : 6/29/2001<br>carol : 6/29/2001<br>carol : 6/29/2001<br>mgross : 6/29/2001<br>mgross : 6/28/2001<br>mgross : 6/27/2001
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="container visible-print-block">
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
<div class="col-md-8 col-md-offset-1">
|
|
|
|
<div>
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
<strong>#</strong> 606072
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
RIPPLING MUSCLE DISEASE 2; RMD2
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div >
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
RIPPLING MUSCLE DISEASE; RMD<br />
|
|
MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 1C, FORMERLY; LGMD1C, FORMERLY
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 709281006;
|
|
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 97238;
|
|
|
|
|
|
<strong>DO:</strong> 0060255;
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
3p25.3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Rippling muscle disease 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
606072
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
CAV3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
601253
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because of evidence that rippling muscle disease-2 (RMD2) is caused by heterozygous mutation in the gene encoding caveolin-3 (CAV3; 601253) on chromosome 3p25. Some patients have been reported with homozygous mutations.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Hereditary rippling muscle disease is an autosomal dominant disorder characterized by mechanically triggered contractions of skeletal muscle. In rippling muscle disease, mechanical stimulation leads to electrically silent muscle contractions that spread to neighboring fibers that cause visible ripples to move over the muscle. RMD is usually inherited as an autosomal dominant trait, but autosomal recessive inheritance has also been reported (Kubisch et al., 2005). </p><p><strong><em>Genetic Heterogeneity of Rippling Muscle Disease</em></strong></p><p>
|
|
Another locus for RMD, designated RMD1 (600332), maps to chromosome 1q41.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Nomenclature</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Some cases of rippling muscle disease-2 were previously classified as a form of limb-girdle muscular dystrophy (type 1C; LGMD1C). Straub et al. (2018), on behalf of the LGMD workshop study group, reclassified LGMD1C as RMD2. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Torbergsen (1975) described myotonia with muscular hypertrophy and hyperirritability in 3 generations (with male-to-male transmission) and maintained that the disorder was distinct from Thomsen myotonia congenita (160800). In the most severely affected persons, unusual rolling muscle contractions were seen. It was not clear that Torbergsen (1975) had demonstrated a definite difference from Thomsen disease. However, Stephan et al. (1994) described a new 44-member pedigree segregating a similar disorder as an autosomal dominant trait. The patients experienced muscle cramps, pain, and stiffness, particularly with exercise. Balling of muscle occurred after percussion, and a characteristic lateral rolling movement of muscle occurred after contraction followed by stretching. Electromyography demonstrated that mechanical stimulation provoked electrically silent contractions. </p><p>Minetti et al. (1998) described 8 patients from 2 different families with what they classified as a form of autosomal dominant limb-girdle muscular dystrophy (LGMD1C) that was associated with a severe deficiency of caveolin-3 in muscle fibers (up to 95% reduction). In both families, initial motor milestones were normal and onset of disease was at about age 5 years. All had calf hypertrophy and mild to moderate proximal muscle weakness, and each adult patient showed a positive Gowers sign. Two patients in 1 family had multiple episodes of muscle cramps after physical effort. Serum creatine kinase levels were elevated 4- to 25-fold. Routine histologic and histochemical studies of muscle biopsies revealed only nonspecific myopathic changes of moderate severity. </p><p>Herrmann et al. (2000) reported a 4-year-old girl with lower limb myalgia and muscle cramps and an elevated serum creatine kinase. Skeletal muscle biopsy showed dystrophic changes and near complete loss of caveolin-3 expression. </p><p>Vorgerd et al. (2001) reported a patient with sporadic RMD who carried a mutation in the CAV3 gene (R26Q; 601253.0007). Muscle biopsy of the patient showed reduced sarcolemmal caveolin-3 with punctuated cytosolic staining, consistent with intracellular retention of an unstable protein. Neuronal nitric oxide synthase (nNOS) expression was normal. Vorgerd et al. (2001) suggested that increased inducibility of nNOS, caused by lack of inhibition by normal caveolin, may contribute to muscle hyperexcitability in RMD. </p><p>Figarella-Branger et al. (2003) reported a 71-year-old woman with the CAV3 R26Q mutation who had mild proximal muscle weakness, scapular winging, slight calf hypertrophy, and a positive Gowers sign. Muscle biopsy showed fibers of various sizes, centrally located nuclei, occasional necrotic and regenerative fibers, decreased dysferlin immunoreactivity, and near absence of caveolin-3. Although this was a late presentation, the authors could not rule out a very slow but myopathic evolution of a putative hyperCKemia in infancy. Figarella-Branger et al. (2003) suggested that this patient had a limb-girdle muscular dystrophy. They emphasized the heterogeneous clinical phenotypes that had been reported in association with this CAV3 mutation. </p><p>Kubisch et al. (2005) reported 2 German sibs who had childhood-onset of RMD by ages 7 and 13. Both patients reported nocturnal myalgia of the legs, showed percussion-induced rapid muscle contractions, and had elevated serum creatine kinase. Neither had cardiac involvement. Genetic analysis identified a homozygous mutation in the CAV3 gene (601253.0010), indicating autosomal recessive inheritance. The unaffected parents were both heterozygous for the mutation. Although the parents were not known to be consanguineous, they both originated from a small village in southern Germany. </p><p>Madrid et al. (2005) reported a father a son with RMD confirmed by genetic analysis (601253.0015). Unusual clinical features in both of these patients included congenital pes equinus deformity and early toe walking, which resolved after orthopedic surgical correction. In addition, the father had nonprogressive mild proximal muscle weakness, and the son demonstrated percussion-induced rapid contractions of the thenar muscles without overt rippling of other muscles. Muscle biopsy from the father showed sparse atrophic myofibers, some hypertrophied fibers, occasional split fibers, increased central myonuclei, and absence of caveolin-3 immunostaining. Electron microscopy showed sarcolemmal papillary projections covered with basal lamina and proliferation of T-tubules in split fibers. Madrid et al. (2005) postulated that hypertrophic myofibers may have split in response to stress. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In the families with rippling muscle disease described by Ricker et al. (1989) and Vorgerd et al. (1999), Betz et al. (2001) found linkage of the disorder to 3p25 at marker D3S1597 with a lod score of 4.68 (theta = 0.05). Betz et al. (2001) identified a maximum 2-point lod score of 6.95 at theta = 0.00 for D3S691. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The transmission pattern of RMD2 in most reported families (e.g., Betz et al., 2001) was consistent with autosomal dominant inheritance. The transmission pattern in some reported families (e.g., Kubisch et al., 2003) was consistent with autosomal recessive inheritance. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 2 families with RMD2, who had been diagnosed with LGMD1C, Minetti et al. (1998) identified heterozygous mutations in the CAV3 gene (601253.0001 and 601253.0002). </p><p>In 2 of 82 patients with muscular dystrophy screened for mutations in the CAV3 gene, McNally et al. (1998) found mutations in the CAV3 gene. One patient was homozygous for a G56S substitution (601253.0003). This patient was the only affected member of her family and had developed proximal muscle weakness in the first decade. This variant was later reclassified as a variant of unknown significance. One patient was heterozygous for a C72W substitution (601253.0004). This patient had progressive proximal muscle weakness beginning in the first decade, but remained ambulatory in the mid-second decade. Her mother and 2 sibs had the identical missense change but did not have symptoms of muscular dystrophy, suggesting that a single abnormal allele is not sufficient to cause the phenotype and that the likely inheritance is autosomal recessive. The authors were unable to determine the nature of the second allele in the proband. McNally (1998) suspected that the phenotype was the result of either loss-of-function mutations or dominant-negative mutations; she doubted that haploinsufficiency leads to the disease. The family was lost to follow-up. </p><p>Among 61 Brazilian patients diagnosed with LGMD, de Paula et al. (2001) identified 2 patients with a heterozygous G56S mutation. Both patients had onset in adulthood, calf hypertrophy, elevated creatine kinase, and difficulty walking. Muscle protein analyses from both patients were normal. Screening of 200 normal Brazilian chromosomes revealed heterozygosity for the G56S change in 4 subjects and a C72W change in 1 subject. The authors concluded that the G56S and C72W changes are rare polymorphisms and do not cause the abnormal phenotype when present in just one allele. They noted the possibility that the variants might act as recessive mutations or interact with other genes involved in the dystrophic process. </p><p>In a Colombian patient and an Italian patient with severe rippling muscle disease, Kubisch et al. (2003) identified 2 different homozygous mutations in the CAV3 gene (601253.0009 and 601253.0010). One patient had muscle stiffness in his legs since the age of 3 and contractures of the Achilles tendon leading to gait disturbances, and the other patient had slowly progressive muscle weakness beginning in early adulthood. Both patients had elevated creatine kinase levels, hypertrophic skeletal muscles, and generalized rapid muscle contractions. Muscle biopsies showed almost complete loss of caveolin-3 expression and reduced dysferlin (603009). Neither patient had family members available for further study. Kubisch et al. (2003) noted that the patients were more severely clinically affected than those with heterozygous mutations. </p><p>In affected members of 5 families with RMD2, including the first-described RMD family reported by Torbergsen (1975) and the families reported by Ricker et al. (1989) and Vorgerd et al. (1999), Betz et al. (2001) identified heterozygous mutations in the CAV3 gene (see 601253.0001, 601253.0005-601253.0007). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Sunada et al. (2001) generated transgenic mice expressing the pro105-to-leu mutant caveolin-3 (P105L; 601253.0001). Mice showed severe myopathy accompanied by the deficiency of caveolin-3 in the sarcolemma, suggesting a dominant-negative effect of mutant caveolin-3. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Betz, R. C., Schoser, B. G. H., Kasper, D., Ricker, K., Ramirez, A., Stein, V., Torbergsen, T., Lee, Y.-A., Nothen, M. M., Wienker, T. F., Malin, J.-P., Propping, P., Reis, A., Mortier, W., Jentsch, T. J., Vorgerd, M., Kubisch, C.
|
|
<strong>Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease.</strong>
|
|
Nature Genet. 28: 218-219, 2001.
|
|
|
|
|
|
[PubMed: 11431690]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/90050]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
de Paula, F., Vainzof, M., Bernardino, A. L. F., McNally, E., Kunkel, L. M., Zatz, M.
|
|
<strong>Mutations in the caveolin-3 gene: when are they pathogenic?</strong>
|
|
Am. J. Med. Genet. 99: 303-307, 2001.
|
|
|
|
|
|
[PubMed: 11251997]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/1096-8628(2001)9999:9999<::aid-ajmg1168>3.0.co;2-o]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Figarella-Branger, D., Pouget, J., Bernard, R., Krahn, M., Fernandez, C., Levy, N., Pellissier, J. F.
|
|
<strong>Limb-girdle muscular dystrophy in a 71-year-old woman with an R27Q mutation in the CAV3 gene.</strong>
|
|
Neurology 61: 562-564, 2003.
|
|
|
|
|
|
[PubMed: 12939441]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000076486.57572.5c]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Herrmann, R., Straub, V., Blank, M., Kutzick, C., Franke, N., Jacob, E. N., Lenard, H.-G., Kroger, S., Voit, T.
|
|
<strong>Dissociation of the dystroglycan complex in caveolin-3-deficient limb girdle muscular dystrophy.</strong>
|
|
Hum. Molec. Genet. 9: 2335-2340, 2000.
|
|
|
|
|
|
[PubMed: 11001938]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/oxfordjournals.hmg.a018926]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kubisch, C., Ketelsen, U.-P., Goebel, I., Omran, H.
|
|
<strong>Autosomal recessive rippling muscle disease with homozygous CAV3 mutations. (Letter)</strong>
|
|
Ann. Neurol. 57: 303-304, 2005.
|
|
|
|
|
|
[PubMed: 15668980]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.20350]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kubisch, C., Schoser, B. G. H., v. During, M., Betz, R. C., Goebel, H.-H., Zahn, S., Ehrbrecht, A., Aasly, J., Schroers, A., Popovic, N., Lochmuller, H., Schroder, J. M., Bruning, T., Malin, J.-P., Fricke, B., Meinck, H.-M., Torbergsen, T., Engels, H., Voss, B., Vorgerd, M.
|
|
<strong>Homozygous mutations in caveolin-3 cause a severe form of rippling muscle disease.</strong>
|
|
Ann. Neurol. 53: 512-520, 2003.
|
|
|
|
|
|
[PubMed: 12666119]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.10501]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Madrid, R. E., Kubisch, C., Hays, A. P.
|
|
<strong>Early-onset toe walking in rippling muscle disease due to a new caveolin-3 gene mutation.</strong>
|
|
Neurology 65: 1301-1303, 2005.
|
|
|
|
|
|
[PubMed: 16247063]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000180963.85963.73]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McNally, E. M., de Sa Moreira, E., Duggan, D. J., Bonnemann, C. G., Lisanti, M. P., Lidov, H. G. W., Vainzof, M., Passos-Bueno, M. R., Hoffman, E. P., Zatz, M., Kunkel, L. M.
|
|
<strong>Caveolin-3 in muscular dystrophy.</strong>
|
|
Hum. Molec. Genet. 7: 871-877, 1998.
|
|
|
|
|
|
[PubMed: 9536092]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/7.5.871]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McNally, E. M.
|
|
<strong>Personal Communication.</strong>
|
|
Chicago, Ill. 6/8/1998.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Minetti, C., Sotgia, F., Bruno, C., Scartezzini, P., Broda, P., Bado, M., Masetti, E., Mazzocco, M., Egeo, A., Donati, M. A., Volonte, D., Galbiati, F., Cordone, G., Bricarelli, F. D., Lisanti, M. P., Zara, F.
|
|
<strong>Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy.</strong>
|
|
Nature Genet. 18: 365-368, 1998.
|
|
|
|
|
|
[PubMed: 9537420]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0498-365]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ricker, K., Moxley, R. T., Rohkamm, R.
|
|
<strong>Rippling muscle disease.</strong>
|
|
Arch. Neurol. 46: 405-408, 1989.
|
|
|
|
|
|
[PubMed: 2705900]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archneur.1989.00520400065020]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stephan, D. A., Buist, N. R. M., Chittenden, A. B., Ricker, K., Zhou, J., Hoffman, E. P.
|
|
<strong>A rippling muscle disease gene is localized to 1q41: evidence for multiple genes.</strong>
|
|
Neurology 44: 1915-1920, 1994.
|
|
|
|
|
|
[PubMed: 7936247]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.44.10.1915]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Straub, V., Murphy, A., Udd, B.
|
|
<strong>229th ENMC international workshop: limb girdle muscular dystrophies--nomenclature and reformed classification, Naarden, the Netherlands, 17-19 March 2017.</strong>
|
|
Neuromusc. Disord. 28: 702-710, 2018.
|
|
|
|
|
|
[PubMed: 30055862]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.nmd.2018.05.007]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sunada, Y., Ohi, H., Hase, A., Ohi, H., Hosono, T., Arata, S., Higuchi, S., Matsumura, K., Shimizu, T.
|
|
<strong>Transgenic mice expressing mutant caveolin-3 show severe myopathy associated with increased nNOS activity.</strong>
|
|
Hum. Molec. Genet. 10: 173-178, 2001.
|
|
|
|
|
|
[PubMed: 11159934]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/10.3.173]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Torbergsen, T.
|
|
<strong>A family with dominant hereditary myotonia, muscular hypertrophy, and increased muscular irritability, distinct from myotonia congenita Thomsen.</strong>
|
|
Acta Neurol. Scand. 51: 225-232, 1975.
|
|
|
|
|
|
[PubMed: 1146501]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1600-0404.1975.tb07603.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vorgerd, M., Bolz, H., Patzold, T., Kubisch, C., Malin, J.-P., Mortier, W.
|
|
<strong>Phenotypic variability in rippling muscle disease.</strong>
|
|
Neurology 52: 1453-1459, 1999.
|
|
|
|
|
|
[PubMed: 10227634]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.52.7.1453]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vorgerd, M., Ricker, K., Ziemssen, F., Kress, W., Goebel, H. H., Nix, W. A., Kubisch, C., Schoser, B. G. H., Mortier, W.
|
|
<strong>A sporadic case of rippling muscle disease caused by a de novo caveolin-3 mutation.</strong>
|
|
Neurology 57: 2273-2277, 2001.
|
|
|
|
|
|
[PubMed: 11756609]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.57.12.2273]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 2/5/2007<br>Cassandra L. Kniffin - updated : 4/27/2005<br>Cassandra L. Kniffin - updated : 6/2/2003<br>Cassandra L. Kniffin - updated : 12/30/2002
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh : 6/27/2001
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 11/02/2022<br>carol : 11/01/2022<br>carol : 09/27/2018<br>carol : 09/26/2018<br>carol : 09/25/2018<br>carol : 03/27/2017<br>carol : 04/30/2012<br>terry : 3/22/2012<br>wwang : 2/9/2007<br>ckniffin : 2/5/2007<br>wwang : 5/10/2005<br>ckniffin : 4/27/2005<br>carol : 6/6/2003<br>ckniffin : 6/2/2003<br>cwells : 1/7/2003<br>ckniffin : 12/30/2002<br>terry : 3/28/2002<br>carol : 6/29/2001<br>carol : 6/29/2001<br>carol : 6/29/2001<br>mgross : 6/29/2001<br>mgross : 6/28/2001<br>mgross : 6/27/2001
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div id="mimFooter">
|
|
|
|
|
|
<div class="container ">
|
|
<div class="row">
|
|
<br />
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="hidden-print mim-footer">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="visible-print-block mim-footer" style="position: relative;">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
<br />
|
|
Printed: March 13, 2025
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
|
|
<div class="modal-dialog" role="document">
|
|
<div class="modal-content">
|
|
<div class="modal-header">
|
|
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">×</span></button>
|
|
<h4 class="modal-title" id="mimDonationPopupModalTitle">
|
|
OMIM Donation:
|
|
</h4>
|
|
</div>
|
|
<div class="modal-body">
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Dear OMIM User,
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
To ensure long-term funding for the OMIM project, we have diversified
|
|
our revenue stream. We are determined to keep this website freely
|
|
accessible. Unfortunately, it is not free to produce. Expert curators
|
|
review the literature and organize it to facilitate your work. Over 90%
|
|
of the OMIM's operating expenses go to salary support for MD and PhD
|
|
science writers and biocurators. Please join your colleagues by making a
|
|
donation now and again in the future. Donations are an important
|
|
component of our efforts to ensure long-term funding to provide you the
|
|
information that you need at your fingertips.
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Thank you in advance for your generous support, <br />
|
|
Ada Hamosh, MD, MPH <br />
|
|
Scientific Director, OMIM <br />
|
|
</p>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div class="modal-footer">
|
|
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
</body>
|
|
|
|
</html>
|
|
|
|
|