7996 lines
730 KiB
Text
7996 lines
730 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
|
|
|
|
- *603506 - LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 5; LRP5
|
|
|
|
|
|
- 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=603506"><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">*603506</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="#geneMap"><strong>Gene-Phenotype Relationships</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="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</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="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/603506">Table View</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="mimGenome">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000162337;t=ENST00000294304" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=4041" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=603506" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</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="mimDna">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000162337;t=ENST00000294304" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001291902,NM_002335,XM_005273994,XM_011545029,XM_011545030,XM_011545031,XM_017017735,XM_017017736,XM_047426948,XM_047426949,XM_047426950,XR_001747874" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_002335" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=603506" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</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="mimProtein">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://hprd.org/summary?hprd_id=04616&isoform_id=04616_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.proteinatlas.org/search/LRP5" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/protein/3582145,3641527,3831748,14028618,62512139,119595111,119595112,119709832,187956357,530396780,631790829,767968172,767968175,767968177,1034573670,1034573673,1134667149,1134667151,1134667153,2217282863,2217282865,2217282867,2220275174,2220275176,2462525216,2462525218,2462525220,2462525222,2462525224,2462525226,2462525228,2462525230,2462525232" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.uniprot.org/uniprotkb/O75197" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</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="mimGeneInfo">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Gene Info</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="http://biogps.org/#goto=genereport&id=4041" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000162337;t=ENST00000294304" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=LRP5" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=LRP5" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+4041" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
|
|
|
|
|
|
|
|
<dd><a href="http://v1.marrvel.org/search/gene/LRP5" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
|
|
|
|
|
|
|
|
<dd><a href="https://monarchinitiative.org/NCBIGene:4041" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gene/4041" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr11&hgg_gene=ENST00000816739.1&hgg_start=68298412&hgg_end=68449275&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</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="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed 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 mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:6697" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:6697" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://medlineplus.gov/genetics/gene/lrp5" 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=603506[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>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=603506[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.deciphergenomics.org/gene/LRP5/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000162337" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ebi.ac.uk/gwas/search?query=LRP5" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.gwascentral.org/search?q=LRP5" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=LRP5" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.LOVD.nl/LRP5" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=LRP5&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.pharmgkb.org/gene/PA30455" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</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/gene/HGNC:6697" 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="https://flybase.org/reports/FBgn0000119.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mousephenotype.org/data/genes/MGI:1278315" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://v1.marrvel.org/search/gene/LRP5#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.informatics.jax.org/marker/MGI:1278315" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gene/4041/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=4041" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-050518-2" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</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="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:4041" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://reactome.org/content/query?q=LRP5&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</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> 1264041000, 254112001, 254131007<br />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
603506
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 5; LRP5
|
|
|
|
</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">
|
|
LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 7; LRP7<br />
|
|
LR3
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=LRP5" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">LRP5</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/11/683?start=-3&limit=10&highlight=683">11q13.2</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr11:68298412-68449275&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">11:68,298,412-68,449,275</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=601884,144750,601813,607634,259770,617875" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="6">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/11/683?start=-3&limit=10&highlight=683">
|
|
11q13.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
[Bone mineral density variability 1]
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/601884"> 601884 </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>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Endosteal hyperostosis
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/144750"> 144750 </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>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Exudative vitreoretinopathy 4
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/601813"> 601813 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</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>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Osteopetrosis, autosomal dominant 1
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/607634"> 607634 </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>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Osteoporosis-pseudoglioma syndrome
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/259770"> 259770 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Polycystic liver disease 4 with or without kidney cysts
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/617875"> 617875 </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>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<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/603506" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/603506" 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>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<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>
|
|
<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>The LRP5 gene encodes a transmembrane protein that acts as a coreceptor with Frizzled protein family members (e.g., FZD1, <a href="/entry/603408">603408</a>) for transducing signals by Wnt proteins (see <a href="/entry/164820">164820</a>) (summary by <a href="#8" class="mim-tip-reference" title="Cnossen, W. R., te Morsche, R. H. M., Hoischen, A., Gilissen, C., Chrispijn, M., Venselaar, H., Mehdi, S., Bergmann, C., Veltman, J. A., Drenth, J. P. H. <strong>Whole-exome sequencing reveals LRP5 mutations and canonical Wnt signaling associated with hepatic cystogenesis.</strong> Proc. Nat. Acad. Sci. 111: 5343-5348, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24706814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24706814</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24706814[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1309438111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24706814">Cnossen et al., 2014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24706814" 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="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Members of the low density lipoprotein receptor (LDLR) family are cell surface proteins that bind and internalize ligands in the process of receptor-mediated endocytosis. To identify candidate genes for the type I diabetes IDDM4 (<a href="/entry/600319">600319</a>) locus in 11q13, <a href="#16" class="mim-tip-reference" title="Hey, P. J., Twells, R. C. J., Phillips, M. S., Nakagawa, Y., Brown, S. D., Kawaguchi, Y., Cox, R., Xie, G., Dugan, V., Hammond, H., Metzker, M. L., Todd, J. A., Hess, J. F. <strong>Cloning of a novel member of the low-density lipoprotein receptor family.</strong> Gene 216: 103-111, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9714764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9714764</a>] [<a href="https://doi.org/10.1016/s0378-1119(98)00311-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9714764">Hey et al. (1998)</a> constructed an approximately 200-kb cosmid and BAC contig of this region. By DNA sequencing and by searching sequence databases, they identified a novel member of the LDLR family, which they named LDLR-related protein-5 (LRP5). The LRP5 cDNA encodes a deduced 1,615-amino acid protein containing conserved modules characteristic of the LDLR family, including a putative signal peptide, 4 epidermal growth factor (EGF) repeats with associated spacer domains, 3 LDLR repeats, a single transmembrane-spanning domain, and a cytoplasmic domain. The extracellular domain of LRP5 contains 6 potential N-linked glycosylation sites. Of the known family members, LRP5 is most closely related to LRP1 (<a href="/entry/107770">107770</a>). However, LRP5 has a unique organization of EGF and LDLR repeats compared to other LDLR family members and likely represents a new category in this family. Northern blot analysis detected an approximately 5.1- to 5.6-kb LRP5 mRNA in a variety of human tissues, with the highest level of expression in the liver. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9714764" 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="#16" class="mim-tip-reference" title="Hey, P. J., Twells, R. C. J., Phillips, M. S., Nakagawa, Y., Brown, S. D., Kawaguchi, Y., Cox, R., Xie, G., Dugan, V., Hammond, H., Metzker, M. L., Todd, J. A., Hess, J. F. <strong>Cloning of a novel member of the low-density lipoprotein receptor family.</strong> Gene 216: 103-111, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9714764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9714764</a>] [<a href="https://doi.org/10.1016/s0378-1119(98)00311-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9714764">Hey et al. (1998)</a> cloned a mouse Lrp5 cDNA and found that the deduced protein is 94% identical to human LRP5. Using immunohistochemistry in Lrp5 knockout mice, <a href="#18" class="mim-tip-reference" title="Kato, M., Patel, M. S., Levasseur, R., Lobov, I., Chang, B. H.-J., Glass, D. A., II, Hartmann, C., Li, L., Hwang, T.-H., Brayton, C. F., Lang, R. A., Karsenty, G., Chan, L. <strong>Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor.</strong> J. Cell Biol. 157: 303-314, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11956231/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11956231</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11956231[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1083/jcb.200201089" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11956231">Kato et al. (2002)</a> determined that Lrp5 is expressed in the osteoblasts lining the endosteal and trabecular bone surfaces. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11956231+9714764" 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>Independently, <a href="#11" class="mim-tip-reference" title="Dong, Y., Lathrop, W., Weaver, D., Qiu, Q., Cini, J., Bertolini, D., Chen, D. <strong>Molecular cloning and characterization of LR3, a novel LDL receptor family protein with mitogenic activity.</strong> Biochem. Biophys. Res. Commun. 251: 784-790, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9790987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9790987</a>] [<a href="https://doi.org/10.1006/bbrc.1998.9545" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9790987">Dong et al. (1998)</a> isolated an LRP5 cDNA from a human osteoblast cDNA library. The authors designated the encoded protein LR3 to reflect its 3 ligand-binding domains. Dot blot analysis of a variety of human adult and fetal tissues detected highest LR3 expression in the aorta, and Northern blot analysis detected a 5.4-kb LR3 message in all human tissues examined except the brain. <a href="#11" class="mim-tip-reference" title="Dong, Y., Lathrop, W., Weaver, D., Qiu, Q., Cini, J., Bertolini, D., Chen, D. <strong>Molecular cloning and characterization of LR3, a novel LDL receptor family protein with mitogenic activity.</strong> Biochem. Biophys. Res. Commun. 251: 784-790, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9790987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9790987</a>] [<a href="https://doi.org/10.1006/bbrc.1998.9545" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9790987">Dong et al. (1998)</a> demonstrated that mouse NIH 3T3 cells transfected with LRP5 show increased cell proliferation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9790987" 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 situ studies of rat tibia by <a href="#20" class="mim-tip-reference" title="Little, R. D., Carulli, J. P., Del Mastro, R. G., Dupuis, J., Osborne, M., Folz, C., Manning, S. P., Swain, P. M., Zhao, S.-C., Eustace, B., Lappe, M. M., Spitzer, L., and 23 others. <strong>A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait.</strong> Am. J. Hum. Genet. 70: 11-19, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11741193/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11741193</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11741193[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/338450" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11741193">Little et al. (2002)</a> showed expression of LRP5 in areas of bone involved in remodeling. Northern blot analysis revealed that LRP5 was transcribed in human bone tissue as well as in numerous other tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11741193" 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="#8" class="mim-tip-reference" title="Cnossen, W. R., te Morsche, R. H. M., Hoischen, A., Gilissen, C., Chrispijn, M., Venselaar, H., Mehdi, S., Bergmann, C., Veltman, J. A., Drenth, J. P. H. <strong>Whole-exome sequencing reveals LRP5 mutations and canonical Wnt signaling associated with hepatic cystogenesis.</strong> Proc. Nat. Acad. Sci. 111: 5343-5348, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24706814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24706814</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24706814[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1309438111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24706814">Cnossen et al. (2014)</a> found abundant expression of the LRP5 gene in liver tissue, specifically in the epithelium lining bile ducts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24706814" 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>Using in situ hybridization probes in zebrafish embryos, <a href="#37" class="mim-tip-reference" title="Xia, W., Hu, J., Liu, F., Ma, J., Sun, S., Zhang, J., Jin, K., Huang, J., Jiang, N., Wang, X., Li, W., Ma, Z., Ma, D. <strong>New role of LRP5, associated with nonsyndromic autosomal-recessive hereditary hearing loss.</strong> Hum. Mutat. 38: 1421-1431, 2017. Note: Erratum: Hum. Mutat. 39: 882 only, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28677207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28677207</a>] [<a href="https://doi.org/10.1002/humu.23285" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28677207">Xia et al. (2017)</a> observed widespread expression of lrp5 at 24, 30, and 48 hours postfertilization. The authors noted that expression was clustered around the otic vesicle, suggesting that lrp5 might contribute to hearing development. Using immunohistochemistry to identify expression in the mouse inner ear, they observed Lrp5 expression in cochlear sensory epithelial cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28677207" 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>By fluorescence in situ hybridization (FISH), <a href="#16" class="mim-tip-reference" title="Hey, P. J., Twells, R. C. J., Phillips, M. S., Nakagawa, Y., Brown, S. D., Kawaguchi, Y., Cox, R., Xie, G., Dugan, V., Hammond, H., Metzker, M. L., Todd, J. A., Hess, J. F. <strong>Cloning of a novel member of the low-density lipoprotein receptor family.</strong> Gene 216: 103-111, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9714764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9714764</a>] [<a href="https://doi.org/10.1016/s0378-1119(98)00311-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9714764">Hey et al. (1998)</a> mapped a mouse BAC clone containing the Lrp5 gene to chromosome 19, which shows homology of synteny with human 11q13. <a href="#6" class="mim-tip-reference" title="Chen, D., Lathrop, W., Dong, Y. <strong>Molecular cloning of mouse Lrp7(Lr3) cDNA and chromosomal mapping of orthologous genes in mouse and human.</strong> Genomics 55: 314-321, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10049586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10049586</a>] [<a href="https://doi.org/10.1006/geno.1998.5688" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10049586">Chen et al. (1999)</a> mapped the human LRP5 gene to 11q13.4 by FISH and between markers D11S24270 and D11S1975 by radiation hybrid mapping. They mapped the mouse Lrp5 gene to chromosome 19B by FISH. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9714764+10049586" 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="geneStructure" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneStructureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneStructureFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>By genomic sequence analysis, <a href="#14" class="mim-tip-reference" title="Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., Zacharin, M., Oexle, K., and 50 others. <strong>LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.</strong> Cell 107: 513-523, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11719191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11719191</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00571-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11719191">Gong et al. (2001)</a> determined that the LRP5 gene contains 23 coding exons and spans more than 100 kb. <a href="#34" class="mim-tip-reference" title="Twells, R. C. J., Metzker, M. L., Brown, S. D., Cox, R., Garey, C., Hammond, H., Hey, P. J., Levy, E., Nakagawa, Y., Philips, M. S., Todd, J. A., Hess, J. F. <strong>The sequence and gene characterization of a 400-kb candidate region for IDDM4 on chromosome 11q13.</strong> Genomics 72: 231-242, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11401438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11401438</a>] [<a href="https://doi.org/10.1006/geno.2000.6492" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11401438">Twells et al. (2001)</a> determined that the LRP5 gene spans 160 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11719191+11401438" 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="geneFunction" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneFunctionFold" id="mimGeneFunctionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneFunctionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneFunctionFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#14" class="mim-tip-reference" title="Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., Zacharin, M., Oexle, K., and 50 others. <strong>LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.</strong> Cell 107: 513-523, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11719191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11719191</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00571-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11719191">Gong et al. (2001)</a> demonstrated LRP5 expression by osteoblasts in situ and showed that LRP5 can transduce Wnt signaling in vitro via the canonical pathway. They further showed that a mutant secreted form of Lrp5 could reduce bone thickness in mouse calvarial explant cultures. These data indicated that Wnt-mediated signaling via LRP5 affects bone accrual during growth and is important for the establishment of peak bone mass. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11719191" 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="#22" class="mim-tip-reference" title="Mao, J., Wang, J., Liu, B., Pan, W., Farr, G. H., III, Flynn, C., Yuan, H., Takada, S., Kimelman, D., Li, L., Wu, D. <strong>Low-density lipoprotein receptor-related protein-5 binds to axin and regulates the canonical Wnt signaling pathway.</strong> Molec. Cell 7: 801-809, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11336703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11336703</a>] [<a href="https://doi.org/10.1016/s1097-2765(01)00224-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11336703">Mao et al. (2001)</a> identified axin (<a href="/entry/603816">603816</a>) as a protein that interacts with the intracellular domain of LRP5. LRP5, when expressed in fibroblast cells, showed no effect on the canonical Wnt signaling pathway by itself, but acted synergistically with Wnt. In contrast, LRP5 mutants lacking the extracellular domain functioned as constitutively active forms that bound axin and that induced LEF1 (<a href="/entry/153245">153245</a>) activation by destabilizing axin and stabilizing beta-catenin (<a href="/entry/116806">116806</a>). Addition of Wnt caused the translocation of axin to the membrane and enhanced the interaction between axin and LRP5. In addition, the LRP5 sequences involved in interactions with axin were found to be required for LEF1 activation. The authors concluded that the binding of axin to LRP5 is an important part of the Wnt signal transduction pathway. LRP5 also acts as a target for the inhibitory effects of Dickkopf (DKK1; <a href="/entry/605189">605189</a>), another developmental protein, on Wnt signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11336703" 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="#30" class="mim-tip-reference" title="Semenov, M., Tamai, K., He, X. <strong>SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor.</strong> J. Biol. Chem. 280: 26770-26775, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15908424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15908424</a>] [<a href="https://doi.org/10.1074/jbc.M504308200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15908424">Semenov et al. (2005)</a> found that human SOST (<a href="/entry/605740">605740</a>) antagonized Wnt signaling in Xenopus embryos and mammalian cells by binding to the extracellular domains of the Wnt coreceptors Lrp5 and Lrp6 (<a href="/entry/603507">603507</a>) and disrupting Wnt-induced frizzled (see <a href="/entry/603408">603408</a>)-Lrp complex formation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15908424" 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><a href="#33" class="mim-tip-reference" title="Twells, R. C. J., Mein, C. A., Phillips, M. S., Hess, J. F., Veijola, R., Gilbey, M., Bright, M., Metzker, M., Lie, B. A., Kingsnorth, A., Gregory, E., Nakagawa, Y., and 12 others. <strong>Haplotype structure, LD blocks, and uneven recombination within the LRP5 gene.</strong> Genome Res. 13: 845-855, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12727905/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12727905</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12727905[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gr.563703" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12727905">Twells et al. (2003)</a> identified 95 SNPs within a 269-kb region containing LRP5 and its 3 flanking genes in several families of white European origin. They found a high level of recombination across LRP5, including a hotspot region from intron 1 to intron 7, where there were 109 recombinants/Mb (4,882 meioses), in contrast to flanking regions of 14.6 recombinants/Mb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12727905" 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>Osteoporosis-Pseudoglioma Syndrome</em></strong></p><p>
|
|
<a href="#14" class="mim-tip-reference" title="Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., Zacharin, M., Oexle, K., and 50 others. <strong>LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.</strong> Cell 107: 513-523, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11719191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11719191</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00571-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11719191">Gong et al. (2001)</a> showed that LRP5 affects bone mass accrual during growth and identified mutations in the LRP5 gene (e.g., <a href="#0001">603506.0001</a>) that cause autosomal recessive osteoporosis-pseudoglioma syndrome (OPPG; <a href="/entry/259770">259770</a>). They found that obligate carriers of mutant LRP5 genes had reduced bone mass when compared to age- and gender-matched controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11719191" 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="#1" class="mim-tip-reference" title="Ai, M., Heeger, S., Bartels, C. F., Schelling, D. K., Osteoporosis-Pseudoglioma Collaborative Group. <strong>Clinical and molecular findings in osteoporosis-pseudoglioma syndrome.</strong> Am. J. Hum. Genet. 77: 741-753, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16252235/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16252235</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16252235[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/497706" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16252235">Ai et al. (2005)</a> sequenced the coding exons of LRP5 in 37 probands suspected of having OPPG on the basis of the cooccurrence of severe congenital or childhood-onset visual impairment with bone fragility or osteoporosis recognized by young adulthood. They found 2 putative mutant alleles in 26 probands, only 1 mutant allele in 4 probands, and no mutant alleles in 7 probands. Looking for digenic inheritance, they sequenced the genes encoding the functionally related receptor LRP6 (<a href="/entry/603507">603507</a>), an LRP5 coreceptor FZD4 (<a href="/entry/604579">604579</a>), and the LRP5 ligand norrin (NDP; <a href="/entry/300658">300658</a>), in the 4 probands with 1 mutant allele, and, looking for locus heterogeneity, they sequenced FZD4 and NDP in the 7 probands with no mutations; no additional mutations were found. They compared clinical features between probands with and those without LRP5 mutations and found no difference in the severity of skeletal disease, prevalence of cognitive impairment, or family history of consanguinity. However, 4 of the 7 probands without detectable mutations had eye pathology that differed from pathology previously described for OPPG. Since many LRP5 mutations are missense changes, to differentiate between a disease-causing mutation and a benign variant <a href="#1" class="mim-tip-reference" title="Ai, M., Heeger, S., Bartels, C. F., Schelling, D. K., Osteoporosis-Pseudoglioma Collaborative Group. <strong>Clinical and molecular findings in osteoporosis-pseudoglioma syndrome.</strong> Am. J. Hum. Genet. 77: 741-753, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16252235/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16252235</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16252235[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/497706" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16252235">Ai et al. (2005)</a> measured the ability of wildtype and mutant LRP5 to transduce Wnt (see <a href="/entry/164820">164820</a>) and Norrin signal ex vivo. Each of the 7 OPPG mutations tested had reduced signal transduction compared with wildtype mutations. These results indicated that early bilateral vitreoretinal eye pathology coupled with skeletal fragility is a strong predictor of LRP5 mutation and that mutations in LRP5 cause OPPG by impairing WNT and Norrin signal transduction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16252235" 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>Familial Exudative Vitreoretinopathy 4</em></strong></p><p>
|
|
Familial exudative vitreoretinopathy (see EVR1; <a href="/entry/133780">133780</a>) is an inherited disorder of retinal vessel development (<a href="#4" class="mim-tip-reference" title="Benson, W. E. <strong>Familial exudative vitreoretinopathy.</strong> Trans. Am. Ophthal. Soc. 93: 473-521, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8719692/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8719692</a>]" pmid="8719692">Benson, 1995</a>). EVR1 is caused by mutation in the FZD4 gene (<a href="/entry/604579">604579</a>) on chromosome 11q14.2 and has been demonstrated in many of the linked families. The LRP5 gene on chromosome 11q13.4 came under suspicion as a candidate gene for FEVR because of involvement of the eyes in some disorders, notably OPPG, which are caused by LRP5 mutation. In affected members of 6 different families with autosomal dominant EVR4 (<a href="/entry/601813">601813</a>), <a href="#32" class="mim-tip-reference" title="Toomes, C., Bottomley, H. M., Jackson, R. M., Towns, K. V., Scott, S., Mackey, D. A., Craig, J. E., Jiang, L., Yang, Z., Trembath, R., Woodruff, G., Gregory-Evans, C. Y., Gregory-Evans, K., Parker, M. J., Black, G. C. M., Downey, L. M., Zhang, K., Inglehearn, C. F. <strong>Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q.</strong> Am. J. Hum. Genet. 74: 721-730, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15024691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15024691</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15024691[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/383202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15024691">Toomes et al. (2004)</a> identified 6 different heterozygous mutations in the LRP5 gene (see, e.g., <a href="#0020">603506.0020</a>-<a href="#0021">603506.0021</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15024691+8719692" 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="Jiao, X., Ventruto, V., Trese, M. T., Shastry, B. S., Hejtmancik, J. F. <strong>Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5.</strong> Am. J. Hum. Genet. 75: 878-884, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15346351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15346351</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15346351[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/425080" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15346351">Jiao et al. (2004)</a> studied 3 consanguineous families of European descent in which autosomal recessive FEVR was diagnosed in multiple individuals. Sequencing of LRP5 showed, in all 3 families, homozygosity for mutation in LRP5: R570Q (<a href="#0022">603506.0022</a>), R752G (<a href="#0023">603506.0023</a>), and E1367K (<a href="#0024">603506.0024</a>). Thus, mutations in the LRP5 gene can cause autosomal recessive as well as autosomal dominant FEVR. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15346351" 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="#26" class="mim-tip-reference" title="Qin, M., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K., Kondo, H. <strong>Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes.</strong> Hum. Mutat. 26: 104-112, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15981244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15981244</a>] [<a href="https://doi.org/10.1002/humu.20191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15981244">Qin et al. (2005)</a> identified 9 novel mutations in the LRP5 gene (see, e.g., <a href="#0025">603506.0025</a>-<a href="#0028">603506.0028</a>) in Japanese patients with FEVR. Four families showed autosomal dominant inheritance, and 2 families showed autosomal recessive inheritance. One family was found to have a heterozygous mutation in the LRP5 gene (<a href="#0026">603506.0026</a>) and a heterozygous mutation in the FZD4 gene (<a href="/entry/604579#0003">604579.0003</a>) on the same chromosome. <a href="#26" class="mim-tip-reference" title="Qin, M., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K., Kondo, H. <strong>Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes.</strong> Hum. Mutat. 26: 104-112, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15981244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15981244</a>] [<a href="https://doi.org/10.1002/humu.20191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15981244">Qin et al. (2005)</a> also found that patients with mutations in the LRP5 gene showed reduced bone mineral density and suggested that it is a common feature in patients with EVR4. <a href="#26" class="mim-tip-reference" title="Qin, M., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K., Kondo, H. <strong>Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes.</strong> Hum. Mutat. 26: 104-112, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15981244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15981244</a>] [<a href="https://doi.org/10.1002/humu.20191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15981244">Qin et al. (2005)</a> proposed that OPPG and EVR4 are part of a single phenotypic spectrum with both ocular and bone manifestations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15981244" 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>Using standard PCR-based sequencing, <a href="#24" class="mim-tip-reference" title="Narumi, S., Numakura, C., Shiihara, T., Seiwa, C., Nozaki, Y., Yamagata, T., Momoi, M. Y., Watanabe, Y., Yoshino, M., Matsuishi, T., Nishi, E., Kawame, H., Akahane, T., Nishimura, G., Emi, M., Hasegawa, T. <strong>Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma syndrome: identification of a 7.2-kb microdeletion using oligonucleotide tiling microarray.</strong> Am. J. Med. Genet. 152A: 133-140, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20034086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20034086</a>] [<a href="https://doi.org/10.1002/ajmg.a.33177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20034086">Narumi et al. (2010)</a> analyzed the LRP5 gene in 4 male Japanese patients with typical skeletal and ocular features of OPPG and identified compound heterozygosity for 1 nonsense and 4 missense mutations in 3 of the patients (<a href="#0025">603506.0025</a> and <a href="#0029">603506.0029</a>-<a href="#0032">603506.0032</a>). In the fourth patient, they identified only heterozygosity for a splice site mutation (<a href="#0033">603506.0033</a>) by sequencing; however, using custom-designed oligonucleotide tiling array CGH targeted to a 600-kb genomic region harboring LRP5, <a href="#24" class="mim-tip-reference" title="Narumi, S., Numakura, C., Shiihara, T., Seiwa, C., Nozaki, Y., Yamagata, T., Momoi, M. Y., Watanabe, Y., Yoshino, M., Matsuishi, T., Nishi, E., Kawame, H., Akahane, T., Nishimura, G., Emi, M., Hasegawa, T. <strong>Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma syndrome: identification of a 7.2-kb microdeletion using oligonucleotide tiling microarray.</strong> Am. J. Med. Genet. 152A: 133-140, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20034086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20034086</a>] [<a href="https://doi.org/10.1002/ajmg.a.33177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20034086">Narumi et al. (2010)</a> identified a 7.2-kb microdeletion within the LRP5 gene (<a href="#0034">603506.0034</a>) on the patient's second allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20034086" 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>Association with Bone Density Variation</em></strong></p><p>
|
|
<a href="#20" class="mim-tip-reference" title="Little, R. D., Carulli, J. P., Del Mastro, R. G., Dupuis, J., Osborne, M., Folz, C., Manning, S. P., Swain, P. M., Zhao, S.-C., Eustace, B., Lappe, M. M., Spitzer, L., and 23 others. <strong>A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait.</strong> Am. J. Hum. Genet. 70: 11-19, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11741193/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11741193</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11741193[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/338450" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11741193">Little et al. (2002)</a> identified a gly171-to-val mutation in the LRP5 gene (G171V; <a href="#0013">603506.0013</a>) that results in an autosomal dominant high bone mass trait (see <a href="/entry/601884">601884</a>). <a href="#5" class="mim-tip-reference" title="Boyden, L. M., Mao, J., Belsky, J., Mitzner, L., Farhi, A., Mitnick, M. A., Wu, D., Insogna, K., Lifton, R. P. <strong>High bone density due to a mutation in LDL-receptor-related protein 5.</strong> New Eng. J. Med. 346: 1513-1521, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12015390/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12015390</a>] [<a href="https://doi.org/10.1056/NEJMoa013444" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12015390">Boyden et al. (2002)</a> found the same LRP5 mutation in a family with autosomal dominant high bone density associated with square jaw and torus palatinus. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12015390+11741193" 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="#36" class="mim-tip-reference" title="Van Wesenbeeck, L., Cleiren, E., Gram, J., Beals, R. K., Benichou, O., Scopelliti, D., Key, L., Renton, T., Bartels, C., Gong, Y., Warman, M. L., de Vernejoul, M.-C., Bollerslev, J., Van Hul, W. <strong>Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density.</strong> Am. J. Hum. Genet. 72: 763-771, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12579474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12579474</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12579474[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/368277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12579474">Van Wesenbeeck et al. (2003)</a> performed mutation analysis of the LRP5 gene in 10 families or isolated patients with various conditions with an increased bone density, including endosteal hyperostosis (<a href="/entry/144750">144750</a>), van Buchem disease (see <a href="/entry/144750">144750</a>), and osteopetrosis type I. Direct sequencing of the LRP5 gene revealed 19 sequence variants, 13 of which were confirmed as polymorphisms, with the remaining 6 novel missense mutations considered likely disease causing (see <a href="#0014">603506.0014</a>-<a href="#0018">603506.0018</a>). Like the G171V mutation (G171V; <a href="#0013">603506.0013</a>), which causes the high bone mass phenotype, all mutations were located in the amino-terminal part of the gene, before the first epidermal growth factor-like domain. These results indicated that, despite the different diagnoses that could be made, conditions with an increased bone density affecting mainly the cortices of the long bones and the skull are often caused by mutations in the LRP5 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12579474" 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="#12" class="mim-tip-reference" title="Ferrari, S. L., Deutsch, S., Choudhury, U., Chevalley, T., Bonjour, J.-P., Dermitzakis, E. T., Rizzoli, R., Antonarakis, S. E. <strong>Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with variation in vertebral bone mass, vertebral bone size, and stature in whites.</strong> Am. J. Hum. Genet. 74: 866-875, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15077203/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15077203</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15077203[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/420771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15077203">Ferrari et al. (2004)</a> tested the hypothesis that polymorphisms in the LRP5 gene contribute to bone mass determination in the general population. In a cross-sectional study of 889 healthy whites of both sexes, they found significant association for a missense substitution in exon 9 with lumbar spine bone mineral content, with bone area, and with stature. The associations were observed mainly in adult men, in whom LRP5 polymorphisms accounted for less than 15% of the variance of the traits. Haplotype analysis suggested that additional genetic variation within the region may contribute to bone mass and size determination. In a study of 1-year gain in vertebral bone mass and size in prepubertal children, they found a significant association in males but not females. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15077203" 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="#23" class="mim-tip-reference" title="Mizuguchi, T., Furuta, I., Watanabe, Y., Tsukamoto, K., Tomita, H., Tsujihata, M., Ohta, T., Kishino, T., Matsumoto, N., Minakami, H., Niikawa, N., Yoshiura, K. <strong>LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant for bone mineral density.</strong> J. Hum. Genet. 49: 80-86, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14727154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14727154</a>] [<a href="https://doi.org/10.1007/s10038-003-0111-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14727154">Mizuguchi et al. (2004)</a> performed an association study between bone mineral density (BMD) and 9 candidate genes in 481 healthy Japanese women. They found that only LRP5 showed a significant association with BMD. A follow-up case-control study of 126 women with osteoporosis (see <a href="/entry/166710">166710</a>) and 131 normal controls revealed a significant difference in allelic frequency of the LRP5 2220C-T SNP (<a href="#0019">603506.0019</a>) (p = 0.009). The authors suggested that LRP5 is a BMD determinant and contributes to a risk of osteoporosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14727154" 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>Association with Obesity</em></strong></p><p>
|
|
<a href="#15" class="mim-tip-reference" title="Guo, Y., Xiong, D., Shen, H., Zhao, L., Xiao, P., Guo, Y., Wang, W., Yang, T., Recker, R. R., Deng, H. <strong>Polymorphisms of the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with obesity phenotypes in a large family-based association study.</strong> J. Med. Genet. 43: 798-803, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16723389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16723389</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16723389[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmg.2006.041715" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16723389">Guo et al. (2006)</a> genotyped 1,873 Caucasian individuals from 405 nuclear families for SNPs and haplotypes of the LRP5 gene and found that the common allele A for SNP4 (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs4988300;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs4988300</a>) and the minor allele G for SNP6 (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs634008;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs634008</a>) were significantly associated with obesity and body mass index (BMI). Significant associations were also observed between the common haplotype A-G-G-G in block 2 (intron 1) with obesity, BMI, and fat mass (p less than 0.001, p less than 0.001, and p = 0.003, respectively). <a href="#15" class="mim-tip-reference" title="Guo, Y., Xiong, D., Shen, H., Zhao, L., Xiao, P., Guo, Y., Wang, W., Yang, T., Recker, R. R., Deng, H. <strong>Polymorphisms of the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with obesity phenotypes in a large family-based association study.</strong> J. Med. Genet. 43: 798-803, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16723389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16723389</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16723389[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmg.2006.041715" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16723389">Guo et al. (2006)</a> concluded that intronic variants of the LRP5 gene are markedly associated with obesity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16723389" 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>Polycystic Liver Disease 4 with or without Kidney Cysts</em></strong></p><p>
|
|
In affected individuals from 4 unrelated families with polycystic liver disease-4 with or without kidney cysts (PCLD4; <a href="/entry/617875">617875</a>), <a href="#8" class="mim-tip-reference" title="Cnossen, W. R., te Morsche, R. H. M., Hoischen, A., Gilissen, C., Chrispijn, M., Venselaar, H., Mehdi, S., Bergmann, C., Veltman, J. A., Drenth, J. P. H. <strong>Whole-exome sequencing reveals LRP5 mutations and canonical Wnt signaling associated with hepatic cystogenesis.</strong> Proc. Nat. Acad. Sci. 111: 5343-5348, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24706814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24706814</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24706814[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1309438111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24706814">Cnossen et al. (2014)</a> identified 4 different heterozygous missense mutations in the in the LRP5 gene (<a href="#0035">603506.0035</a>-<a href="#0038">603506.0038</a>). Two mutations affected the extracellular domain, and 2 affected the intracellular domain. The mutation in the first family was found by whole-exome sequencing and confirmed by Sanger sequencing; the 3 other mutations were found by direct sequencing of the LRP5 gene in a cohort of 150 probands with cystic liver disease. The mutations segregated with the disorder in the families, with some evidence for age-dependent incomplete penetrance. In vitro functional expression studies of 2 of the variants showed that they resulted in decreased WNT (see, e.g., <a href="/entry/164820">164820</a>) signaling activation in response to Wnt3a (<a href="/entry/606359">606359</a>) compared to wildtype, as well as altered expression of some target genes in this pathway. None of the patients carrying mutations had evidence of clinical features of other LRP5-related disorders, including bone density or ocular abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24706814" 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>Associations Pending Confirmation</em></strong></p><p>
|
|
---Deafness, Autosomal Recessive</p><p>In a Chinese family (WZ-01) in which a brother and sister had nonsyndromic postlingual hearing loss (see <a href="/entry/220290">220290</a>) and were negative for mutation in common deafness-associated genes, <a href="#37" class="mim-tip-reference" title="Xia, W., Hu, J., Liu, F., Ma, J., Sun, S., Zhang, J., Jin, K., Huang, J., Jiang, N., Wang, X., Li, W., Ma, Z., Ma, D. <strong>New role of LRP5, associated with nonsyndromic autosomal-recessive hereditary hearing loss.</strong> Hum. Mutat. 38: 1421-1431, 2017. Note: Erratum: Hum. Mutat. 39: 882 only, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28677207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28677207</a>] [<a href="https://doi.org/10.1002/humu.23285" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28677207">Xia et al. (2017)</a> performed whole-exome sequencing and identified homozygosity for a G610W missense mutation in the LRP5 gene that was confirmed by Sanger sequencing. The report indicated that the unaffected parents of the affected sibs were the only other family members analyzed by whole-exome sequencing. The authors stated that the mutation was not found in unaffected family members or in 500 ethnically matched controls. Onset of symptoms occurred in the second decade of life, with tinnitus and hearing impairment involving primarily the low and middle frequencies, resulting in a 'valley-shaped' audiogram. CT and MRI imaging of the inner ear was normal. The G610W mutant showed weaker ability than wildtype LRP5 to rescue the lrp5-knockdown phenotype of morphant zebrafish embryos (see ANIMAL MODEL). The authors concluded that LRP5 is a candidate gene for deafness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28677207" 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="genotypePhenotypeCorrelations" class="mim-anchor"></a>
|
|
<h4 href="#mimGenotypePhenotypeCorrelationsFold" id="mimGenotypePhenotypeCorrelationsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGenotypePhenotypeCorrelationsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGenotypePhenotypeCorrelationsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Using a norrin-based reporter assay to analyze the effects of FEVR-causing mutations, <a href="#27" class="mim-tip-reference" title="Qin, M., Kondo, H., Tahira, T., Hayashi, K. <strong>Moderate reduction of Norrin signaling activity associated with the causative missense mutations identified in patients with familial exudative vitreoretinopathy.</strong> Hum. Genet. 122: 615-623, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17955262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17955262</a>] [<a href="https://doi.org/10.1007/s00439-007-0438-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17955262">Qin et al. (2008)</a> demonstrated that a nonsense mutation in FZD4 completely abolished signaling activity, whereas missense mutations in FZD4 and LRP5 caused a moderate level of reduction, and a double missense mutation in both genes caused a severe reduction in activity, correlating roughly with clinical phenotypes. Norrin mutants, however, showed variable effects on signal transduction, and no correlation with clinical phenotypes was observed; norrin mutants also showed impaired cell surface binding. <a href="#27" class="mim-tip-reference" title="Qin, M., Kondo, H., Tahira, T., Hayashi, K. <strong>Moderate reduction of Norrin signaling activity associated with the causative missense mutations identified in patients with familial exudative vitreoretinopathy.</strong> Hum. Genet. 122: 615-623, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17955262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17955262</a>] [<a href="https://doi.org/10.1007/s00439-007-0438-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17955262">Qin et al. (2008)</a> concluded that norrin signaling is involved in FEVR pathogenesis, but suggested the presence of an unknown parallel pathway at the level of receptor/ligand binding as evidenced by the moderate and variable signal reduction lacking a clear genotype/phenotype correlation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17955262" 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="#18" class="mim-tip-reference" title="Kato, M., Patel, M. S., Levasseur, R., Lobov, I., Chang, B. H.-J., Glass, D. A., II, Hartmann, C., Li, L., Hwang, T.-H., Brayton, C. F., Lang, R. A., Karsenty, G., Chan, L. <strong>Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor.</strong> J. Cell Biol. 157: 303-314, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11956231/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11956231</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11956231[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1083/jcb.200201089" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11956231">Kato et al. (2002)</a> generated mice with a targeted disruption of Lrp5 and showed that they develop a low bone mass phenotype. In vivo and in vitro analyses indicated that the phenotype becomes evident postnatally, and demonstrated that it is secondary to decreased osteoblast proliferation and function in a Cbfa1 (<a href="/entry/600211">600211</a>)-independent manner. The mice also displayed persistent embryonic eye vascularization due to a failure of macrophage-induced endothelial cell apoptosis. DNA cotransfection and coimmunoprecipitation experiments showed that Lrp5 binds directly to Wnt proteins. RT-PCR experiments showed that expression of proteins in the Wnt signaling pathway was affected by Lrp5 disruption. The phenotype of the Lrp5-deficient mice phenotype mirrored human osteoporosis-pseudoglioma syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11956231" 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="Clement-Lacroix, P., Ai, M., Morvan, F., Roman-Roman, S., Vayssiere, B., Belleville, C., Estrera, K., Warman, M. L., Baron, R., Rawadi, G. <strong>Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice.</strong> Proc. Nat. Acad. Sci. 102: 17406-17411, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16293698/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16293698</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16293698[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0505259102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16293698">Clement-Lacroix et al. (2005)</a> found that lithium restored bone metabolism and bone mass to near wildtype levels in Lrp5 -/- mice. Lithium activated canonical Wnt signaling in cultured calvarial osteoblasts from Lrp5 -/- mice, and lithium-treated mice had increased expression of Wnt-responsive genes in their bone marrow cells in vivo. <a href="#7" class="mim-tip-reference" title="Clement-Lacroix, P., Ai, M., Morvan, F., Roman-Roman, S., Vayssiere, B., Belleville, C., Estrera, K., Warman, M. L., Baron, R., Rawadi, G. <strong>Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice.</strong> Proc. Nat. Acad. Sci. 102: 17406-17411, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16293698/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16293698</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16293698[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0505259102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16293698">Clement-Lacroix et al. (2005)</a> concluded that lithium enhances bone anabolism, at least in part, by activating the Wnt signaling pathway downstream of LRP5. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16293698" 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>LRP5 plays an essential role in bone accrual and eye development. <a href="#13" class="mim-tip-reference" title="Fujino, T., Asaba, H., Kang, M.-J., Ikeda, Y., Sone, H., Takada, S., Kim, D.-H., Ioka, R. X., Ono, M., Tomoyori, H., Okubo, M., Murase, T., and 13 others. <strong>Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion.</strong> Proc. Nat. Acad. Sci. 100: 229-234, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12509515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12509515</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12509515[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0133792100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12509515">Fujino et al. (2003)</a> showed that LRP5 is also required for normal cholesterol and glucose metabolism. Mice lacking Lrp5 showed increased plasma cholesterol levels when fed a high-fat diet, because of the decreased hepatic clearance of chylomicron remnants. In addition, when fed a normal diet, Lrp5-deficient mice showed a markedly impaired glucose tolerance. The experiments suggested that Wnt/LRP5 signaling contributes to the glucose-induced insulin secretion in islets. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12509515" 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>To study lipoprotein metabolism, <a href="#21" class="mim-tip-reference" title="Magoori, K., Kang, M.-J., Ito, M. R., Kakuuchi, H., Ioka, R. X., Kamataki, A., Kim, D.-H., Asaba, H., Iwasaki, S., Takei, Y. A., Sasaki, M., Usui, S., Okazaki, M., Takahashi, S., Ono, M., Nose, M., Sakai, J., Fujino, T., Yamamoto, T. T. <strong>Severe hypercholesterolemia, impaired fat tolerance, and advanced atherosclerosis in mice lacking both low density lipoprotein receptor-related protein 5 and apolipoprotein E.</strong> J. Biol. Chem. 278: 11331-11336, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12509421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12509421</a>] [<a href="https://doi.org/10.1074/jbc.M211987200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12509421">Magoori et al. (2003)</a> generated mice lacking both apolipoprotein E (apoE; <a href="/entry/107741">107741</a>) and Lrp5. On a normal diet, the double knockout mice older than 4 months of age had 60% higher plasma cholesterol levels than the levels observed with apoE deficiency alone. LRP5 deficiency alone had no significant effects on the plasma cholesterol levels. Analysis showed that the very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions were markedly increased in the double knockout mice. Atherosclerotic lesions in the double knockout mice at age 6 months were severe, with destruction of the internal elastic lamina. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12509421" 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="#38" class="mim-tip-reference" title="Yadav, V. K., Ryu, J.-H., Suda, N., Tanaka, K. F., Gingrich, J. A., Schutz, G., Glorieux, F. H., Chiang, C. Y., Zajac, J. D., Insogna, K. L., Mann, J. J., Hen, R., Ducy, P., Karsenty, G. <strong>Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum.</strong> Cell 135: 825-837, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19041748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19041748</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19041748[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.cell.2008.09.059" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19041748">Yadav et al. (2008)</a> identified Tph1 (<a href="/entry/191060">191060</a>), which encodes the rate-limiting enzyme in serotonin synthesis, as the most highly overexpressed gene in Lrp5 -/- mice. Tph1 expression was also elevated in Lrp5 -/- duodenal cells, its primary site of expression. Decreasing serotonin blood levels normalized bone formation and bone mass in Lrp5 -/- mice, and gut-specific Lrp5 inactivation decreased bone formation in a beta-catenin-independent manner. Moreover, gut-specific activation of Lrp5 or inactivation of Tph1 increased bone mass and prevented ovariectomy-induced bone loss in mice. <a href="#38" class="mim-tip-reference" title="Yadav, V. K., Ryu, J.-H., Suda, N., Tanaka, K. F., Gingrich, J. A., Schutz, G., Glorieux, F. H., Chiang, C. Y., Zajac, J. D., Insogna, K. L., Mann, J. J., Hen, R., Ducy, P., Karsenty, G. <strong>Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum.</strong> Cell 135: 825-837, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19041748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19041748</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19041748[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.cell.2008.09.059" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19041748">Yadav et al. (2008)</a> showed that serotonin determined the extent of bone formation by binding its receptor, Htr1b (<a href="/entry/182131">182131</a>), on osteoblasts and limiting osteoblast proliferation by inhibiting Creb (see <a href="/entry/123810">123810</a>)-mediated cyclin D1 (CCND1; <a href="/entry/168461">168461</a>) expression. <a href="#38" class="mim-tip-reference" title="Yadav, V. K., Ryu, J.-H., Suda, N., Tanaka, K. F., Gingrich, J. A., Schutz, G., Glorieux, F. H., Chiang, C. Y., Zajac, J. D., Insogna, K. L., Mann, J. J., Hen, R., Ducy, P., Karsenty, G. <strong>Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum.</strong> Cell 135: 825-837, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19041748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19041748</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19041748[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.cell.2008.09.059" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19041748">Yadav et al. (2008)</a> concluded that LRP5 inhibits bone formation by inhibiting serotonin production. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19041748" 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="#9" class="mim-tip-reference" title="Cui, Y., Niziolek, P. J., MacDonald, B. T., Zylstra, C. R., Alenina, N., Robinson, D. R., Zhong, Z., Matthes, S., Jacobsen, C. M., Conlon, R. A., Brommage, R., Liu, Q., and 11 others. <strong>Lrp5 functions in bone to regulate bone mass.</strong> Nature Med. 17: 684-691, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21602802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21602802</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21602802[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm.2388" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21602802">Cui et al. (2011)</a> generated mice with osteocyte-specific expression of inducible Lrp5 mutations that cause high bone mass (G171V, <a href="#0013">603506.0013</a>; A214V, <a href="#0017">603506.0017</a>) and observed increased bone mass, bone strength, and bone formation rates in the mutant mice compared to wildtype. Similar studies with a truncating Lrp5 mutation resulted in reduced bone mass in the mutant mice compared to wildtype; inactivation of Lrp5 in the intestine, however, had no significant effect on bone mass. In addition, induction of an Lrp5 mutation in cells that form the appendicular skeleton but not in cells that form the axial skeleton resulted in alterations in bone properties of the limbs but not the spine. <a href="#9" class="mim-tip-reference" title="Cui, Y., Niziolek, P. J., MacDonald, B. T., Zylstra, C. R., Alenina, N., Robinson, D. R., Zhong, Z., Matthes, S., Jacobsen, C. M., Conlon, R. A., Brommage, R., Liu, Q., and 11 others. <strong>Lrp5 functions in bone to regulate bone mass.</strong> Nature Med. 17: 684-691, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21602802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21602802</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21602802[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm.2388" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21602802">Cui et al. (2011)</a> concluded that their findings supported a mechanism in mice in which Lrp5 functions via the canonical Wnt pathway in osteocytes to regulate bone mass rather than regulating bone mass indirectly via other tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21602802" 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="#37" class="mim-tip-reference" title="Xia, W., Hu, J., Liu, F., Ma, J., Sun, S., Zhang, J., Jin, K., Huang, J., Jiang, N., Wang, X., Li, W., Ma, Z., Ma, D. <strong>New role of LRP5, associated with nonsyndromic autosomal-recessive hereditary hearing loss.</strong> Hum. Mutat. 38: 1421-1431, 2017. Note: Erratum: Hum. Mutat. 39: 882 only, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28677207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28677207</a>] [<a href="https://doi.org/10.1002/humu.23285" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28677207">Xia et al. (2017)</a> generated zebrafish morphants with knockdown of lrp5 and observed that the morphants had abnormal numbers of otoliths and smaller otic vesicles than wildtype embryos. In addition, the inner ear structure of morphants was abnormal and disrupted. Morphant neuromasts were smaller and the number of lateral-line neuromasts was lower than in wildtype embryos, and there were fewer hair cells and supporting cells per neuromast. Fewer variable stereocilia were detected in the morphants, and the steriocilia were shorter and thinner than those in wildtype embryos. The morphant phenotype was largely rescued by injection of wildtype LRP5. Morphant zebrafish also showed abnormal swimming behavior, consistent with a defective balance system, and had a reduced C-startle response to sound; LRP5 rescue resulted in about half of the morphants regaining some hearing ability, with increased audio stimulus sensitivity, and swimming postures normalized. Analysis of mRNA expression in morphant and wildtype zebrafish embryos revealed reduced expression in morphants of genes in the Wnt (see <a href="/entry/164820">164820</a>) signaling pathway as well as beta-catenin (CTNNB1; <a href="/entry/116806">116806</a>), and BrdU analysis showed reduced cell proliferation in morphants compared to wildtype zebrafish. The authors suggested that lrp5 knockdown induced inhibition of cell proliferation through the Wnt/beta-catenin signaling pathway, resulting in hearing loss. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28677207" 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="allelicVariants" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<span href="#mimAllelicVariantsFold" id="mimAllelicVariantsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
|
|
</span>
|
|
<strong>38 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/603506" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=603506[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
|
|
|
|
</div>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0001" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, TRP10TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121908660 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908660;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121908660?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908660" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908660" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006646" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006646" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006646</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; <a href="/entry/259770">259770</a>), <a href="#14" class="mim-tip-reference" title="Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., Zacharin, M., Oexle, K., and 50 others. <strong>LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.</strong> Cell 107: 513-523, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11719191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11719191</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00571-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11719191">Gong et al. (2001)</a> identified a homozygous G-to-A transition at nucleotide 29 of the LRP5 gene, resulting in a trp10-to-ter (W10X) mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11719191" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0002" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, ARG428TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908661 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908661;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908661" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908661" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006647 OR RCV001781193 OR RCV002496285 OR RCV003904811" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006647, RCV001781193, RCV002496285, RCV003904811" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006647...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; <a href="/entry/259770">259770</a>), <a href="#14" class="mim-tip-reference" title="Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., Zacharin, M., Oexle, K., and 50 others. <strong>LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.</strong> Cell 107: 513-523, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11719191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11719191</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00571-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11719191">Gong et al. (2001)</a> identified a homozygous C-to-T transition at nucleotide 1282 of the LRP5 gene, resulting in an arg428-to-ter (R428X) mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11719191" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0003" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, 1-BP DEL, 1467G
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1554967141 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1554967141;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1554967141" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1554967141" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006648" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006648" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006648</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; <a href="/entry/259770">259770</a>), <a href="#14" class="mim-tip-reference" title="Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., Zacharin, M., Oexle, K., and 50 others. <strong>LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.</strong> Cell 107: 513-523, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11719191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11719191</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00571-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11719191">Gong et al. (2001)</a> identified a homozygous deletion of G at nucleotide 1467 of the LRP5 gene. This mutation produced a frameshift after asp490 (D490). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11719191" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0004" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, ASP718TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908662 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908662;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908662" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908662" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006649" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006649" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006649</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; <a href="/entry/259770">259770</a>), <a href="#14" class="mim-tip-reference" title="Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., Zacharin, M., Oexle, K., and 50 others. <strong>LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.</strong> Cell 107: 513-523, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11719191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11719191</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00571-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11719191">Gong et al. (2001)</a> identified a homozygous insertion of T at nucleotide 2150 of the LRP5 gene. This mutation produced a stop codon at asp718 (D718X). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11719191" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0005" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, GLN853TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908663 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908663;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908663" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908663" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006650" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006650" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006650</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; <a href="/entry/259770">259770</a>), <a href="#14" class="mim-tip-reference" title="Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., Zacharin, M., Oexle, K., and 50 others. <strong>LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.</strong> Cell 107: 513-523, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11719191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11719191</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00571-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11719191">Gong et al. (2001)</a> identified a homozygous C-to-T transition at nucleotide 2557 of the LRP5 gene, resulting in a gln853-to-ter (Q853X) nonsense mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11719191" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0006" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, 1-BP DEL, 3804A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs80358319 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358319;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs80358319?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80358319" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80358319" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006651" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006651" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006651</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; <a href="/entry/259770">259770</a>), <a href="#14" class="mim-tip-reference" title="Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., Zacharin, M., Oexle, K., and 50 others. <strong>LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.</strong> Cell 107: 513-523, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11719191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11719191</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00571-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11719191">Gong et al. (2001)</a> identified a homozygous deletion of A at nucleotide 3804 of the LRP5 gene. This mutation produced a frameshift after glu1270 (E1270). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11719191" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0007" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, ARG494GLN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908664 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908664;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006652 OR RCV000414333 OR RCV002247255 OR RCV004742219 OR RCV005003340" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006652, RCV000414333, RCV002247255, RCV004742219, RCV005003340" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006652...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; <a href="/entry/259770">259770</a>), <a href="#14" class="mim-tip-reference" title="Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., Zacharin, M., Oexle, K., and 50 others. <strong>LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.</strong> Cell 107: 513-523, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11719191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11719191</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00571-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11719191">Gong et al. (2001)</a> identified a homozygous G-to-A transition at nucleotide 1481 of the LRP5 gene, resulting in an arg494-to-gln (R494Q) mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11719191" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0008" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, ARG570TRP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908665 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908665;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006653 OR RCV001851703 OR RCV002276534" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006653, RCV001851703, RCV002276534" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006653...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; <a href="/entry/259770">259770</a>), <a href="#14" class="mim-tip-reference" title="Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., Zacharin, M., Oexle, K., and 50 others. <strong>LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.</strong> Cell 107: 513-523, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11719191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11719191</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00571-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11719191">Gong et al. (2001)</a> identified a homozygous C-to-T transition at nucleotide 1708 of the LRP5 gene, resulting in an arg570-to-trp (R570W) mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11719191" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0009" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, VAL667MET
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs4988321 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs4988321;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs4988321?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs4988321" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs4988321" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006654 OR RCV000086953 OR RCV000250939 OR RCV002276535 OR RCV002276536 OR RCV002496286 OR RCV004814844" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006654, RCV000086953, RCV000250939, RCV002276535, RCV002276536, RCV002496286, RCV004814844" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006654...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; <a href="/entry/259770">259770</a>), <a href="#14" class="mim-tip-reference" title="Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., Zacharin, M., Oexle, K., and 50 others. <strong>LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.</strong> Cell 107: 513-523, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11719191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11719191</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00571-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11719191">Gong et al. (2001)</a> identified a homozygous G-to-A transition at nucleotide 1999 of the LRP5 gene, resulting in a val667-to-met (V667M) mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11719191" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0010" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, GLU485TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908666 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908666;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006655" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006655" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006655</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; <a href="/entry/259770">259770</a>), <a href="#14" class="mim-tip-reference" title="Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., Zacharin, M., Oexle, K., and 50 others. <strong>LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.</strong> Cell 107: 513-523, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11719191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11719191</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00571-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11719191">Gong et al. (2001)</a> identified a G-to-T transversion at nucleotide 1453 of the LRP5 gene, resulting in a glu485-to-ter (E485X) mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11719191" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0011" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, TRP734TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908667 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908667;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006656" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006656" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006656</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; <a href="/entry/259770">259770</a>), <a href="#14" class="mim-tip-reference" title="Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., Zacharin, M., Oexle, K., and 50 others. <strong>LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.</strong> Cell 107: 513-523, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11719191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11719191</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00571-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11719191">Gong et al. (2001)</a> identified a G-to-A transition at nucleotide 2202 of the LRP5 gene, resulting in a trp734-to-ter (W734X) mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11719191" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0012" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, 1-BP DEL, 2305G
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1554971145 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1554971145;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1554971145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1554971145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006657" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006657" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006657</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; <a href="/entry/259770">259770</a>), <a href="#14" class="mim-tip-reference" title="Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., Zacharin, M., Oexle, K., and 50 others. <strong>LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.</strong> Cell 107: 513-523, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11719191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11719191</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00571-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11719191">Gong et al. (2001)</a> identified a deletion of G at nucleotide 2305 of the LRP5 gene. This mutation produced a frameshift after asp769 (D769). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11719191" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0013" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 HIGH BONE MASS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, GLY171VAL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908668 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908668;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908668" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908668" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006658 OR RCV002276537 OR RCV002512843" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006658, RCV002276537, RCV002512843" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006658...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with high bone mass (see <a href="/entry/601884">601884</a>), <a href="#20" class="mim-tip-reference" title="Little, R. D., Carulli, J. P., Del Mastro, R. G., Dupuis, J., Osborne, M., Folz, C., Manning, S. P., Swain, P. M., Zhao, S.-C., Eustace, B., Lappe, M. M., Spitzer, L., and 23 others. <strong>A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait.</strong> Am. J. Hum. Genet. 70: 11-19, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11741193/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11741193</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11741193[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/338450" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11741193">Little et al. (2002)</a> identified a heterozygous G-to-T transversion in exon 3 of the LRP5 gene, resulting in a gly171-to-val (G171V) change in a predicted beta-propeller module of the LRP5 protein. This change was not found in the DNA from 275 individuals with normal bone mineral density or from 643 randomly chosen, ethnically diverse individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11741193" 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="Boyden, L. M., Mao, J., Belsky, J., Mitzner, L., Farhi, A., Mitnick, M. A., Wu, D., Insogna, K., Lifton, R. P. <strong>High bone density due to a mutation in LDL-receptor-related protein 5.</strong> New Eng. J. Med. 346: 1513-1521, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12015390/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12015390</a>] [<a href="https://doi.org/10.1056/NEJMoa013444" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12015390">Boyden et al. (2002)</a> found the G171V mutation in affected members of a kindred with high bone density, wide and deep mandible, and torus palatinus. Affected members of this family had normal serum calcium and phosphate levels, normal serum levels of parathyroid hormone and vitamin D metabolites, and normal serum levels of acid phosphatase. Serum osteocalcin, a marker of bone formation, was markedly elevated. Affected members of the family had no cranial nerve pulses. They were asymptomatic but noted difficulty staying afloat while swimming. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12015390" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0014" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 OSTEOPETROSIS, AUTOSOMAL DOMINANT 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, GLY171ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908669 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908669;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908669" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908669" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006659" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006659" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006659</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Van Wesenbeeck, L., Cleiren, E., Gram, J., Beals, R. K., Benichou, O., Scopelliti, D., Key, L., Renton, T., Bartels, C., Gong, Y., Warman, M. L., de Vernejoul, M.-C., Bollerslev, J., Van Hul, W. <strong>Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density.</strong> Am. J. Hum. Genet. 72: 763-771, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12579474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12579474</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12579474[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/368277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12579474">Van Wesenbeeck et al. (2003)</a> found a 511G-C transversion in exon 3 of the LRP5 gene, causing a gly171-to-arg (G171R) mutation, in a previously described Belgian family (kindred F) in which at least 3 members were diagnosed with autosomal dominant osteopetrosis type I (OPTA1; <a href="/entry/607634">607634</a>). The father suffered from severe headaches and x-rays showed very dense bones of the skull. His daughter had a very dense cranial base and cortical thickening of the vertebrae and long bones with normal development. His son had dense bones, mainly of the skull. The codon involved in this mutation is the same as that in the gain-of-function gly171-to-val mutation (G171V; <a href="#0013">603506.0013</a>) described in 2 other families by <a href="#20" class="mim-tip-reference" title="Little, R. D., Carulli, J. P., Del Mastro, R. G., Dupuis, J., Osborne, M., Folz, C., Manning, S. P., Swain, P. M., Zhao, S.-C., Eustace, B., Lappe, M. M., Spitzer, L., and 23 others. <strong>A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait.</strong> Am. J. Hum. Genet. 70: 11-19, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11741193/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11741193</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11741193[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/338450" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11741193">Little et al. (2002)</a> and <a href="#5" class="mim-tip-reference" title="Boyden, L. M., Mao, J., Belsky, J., Mitzner, L., Farhi, A., Mitnick, M. A., Wu, D., Insogna, K., Lifton, R. P. <strong>High bone density due to a mutation in LDL-receptor-related protein 5.</strong> New Eng. J. Med. 346: 1513-1521, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12015390/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12015390</a>] [<a href="https://doi.org/10.1056/NEJMoa013444" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12015390">Boyden et al. (2002)</a>. The phenotype was different in those 2 families; the family described by <a href="#20" class="mim-tip-reference" title="Little, R. D., Carulli, J. P., Del Mastro, R. G., Dupuis, J., Osborne, M., Folz, C., Manning, S. P., Swain, P. M., Zhao, S.-C., Eustace, B., Lappe, M. M., Spitzer, L., and 23 others. <strong>A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait.</strong> Am. J. Hum. Genet. 70: 11-19, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11741193/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11741193</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11741193[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/338450" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11741193">Little et al. (2002)</a> had no features other than very dense bones, whereas patients in the other kindred also suffered from a wide, deep mandible and torus palatinus. The clinical and radiologic features of the Belgian family resembled those of the family described by <a href="#20" class="mim-tip-reference" title="Little, R. D., Carulli, J. P., Del Mastro, R. G., Dupuis, J., Osborne, M., Folz, C., Manning, S. P., Swain, P. M., Zhao, S.-C., Eustace, B., Lappe, M. M., Spitzer, L., and 23 others. <strong>A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait.</strong> Am. J. Hum. Genet. 70: 11-19, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11741193/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11741193</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11741193[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/338450" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11741193">Little et al. (2002)</a>, as they did not suffer from an enlarged mandible or torus palatinus. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12015390+11741193+12579474" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0015" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 ENDOSTEAL HYPEROSTOSIS, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
OSTEOPETROSIS, AUTOSOMAL DOMINANT 1, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, ALA242THR
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908670 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908670;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908670" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908670" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006660 OR RCV000006661 OR RCV000383760 OR RCV004742220" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006660, RCV000006661, RCV000383760, RCV004742220" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006660...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Van Wesenbeeck, L., Cleiren, E., Gram, J., Beals, R. K., Benichou, O., Scopelliti, D., Key, L., Renton, T., Bartels, C., Gong, Y., Warman, M. L., de Vernejoul, M.-C., Bollerslev, J., Van Hul, W. <strong>Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density.</strong> Am. J. Hum. Genet. 72: 763-771, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12579474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12579474</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12579474[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/368277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12579474">Van Wesenbeeck et al. (2003)</a> described a 724G-A transition in exon 4 of the LRP5 gene, resulting in an ala242-to-thr (A242T) mutation, in 2 previously described families (kindreds A and B) from Portland, Oregon (<a href="#3" class="mim-tip-reference" title="Beals, R. K. <strong>Endosteal hyperostosis.</strong> J. Bone Joint Surg. Am. 58: 1172-1173, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1002767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1002767</a>]" pmid="1002767">Beals, 1976</a>; <a href="#2" class="mim-tip-reference" title="Beals, R. K., McLoughlin, S. W., Teed, R. L., McDonald, C. <strong>Dominant endosteal hyperostosis: skeletal characteristics and review of the literature.</strong> J. Bone Joint Surg. Am. 83: 1643-1649, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11701785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11701785</a>]" pmid="11701785">Beals et al., 2001</a>) in which members were affected with autosomal dominant endosteal hyperostosis (<a href="/entry/144750">144750</a>). The condition is characterized by cortical thickening of the long bones, with no alteration in external shape, and a remarkable resistance of the bone to fracture. The skeleton was normal in childhood; the affected patients had a normal height, proportion, intelligence, and longevity. Facial metamorphoses occurred in adolescence, as the forehead flattened, the mandible became elongated, and the gonial angle decreased. Torus palatinus developed in the hard palate, which could lead to malocclusion or loss of teeth. The clinical and radiographic features closely resembled those of the kindred described by <a href="#5" class="mim-tip-reference" title="Boyden, L. M., Mao, J., Belsky, J., Mitzner, L., Farhi, A., Mitnick, M. A., Wu, D., Insogna, K., Lifton, R. P. <strong>High bone density due to a mutation in LDL-receptor-related protein 5.</strong> New Eng. J. Med. 346: 1513-1521, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12015390/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12015390</a>] [<a href="https://doi.org/10.1056/NEJMoa013444" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12015390">Boyden et al. (2002)</a>, in whom a gly171-to-val mutation (G171V; <a href="#0013">603506.0013</a>) was identified. The A242T mutation was also present in a previously described Sardinian family (kindred D; <a href="#29" class="mim-tip-reference" title="Scopelliti, D., Orsini, R., Ventucci, D., Carratelli, D. <strong>Malattia di Van Buchem.</strong> Minerva Stomatol. 48: 227-234, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10434540/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10434540</a>]" pmid="10434540">Scopelliti et al., 1999</a>) in which at least 5 members had osteosclerosis of the skull and enlarged mandible. The mutation was also present in a French family in which an affected proband and his brother had autosomal dominant osteopetrosis type I (OPTA1; <a href="/entry/607634">607634</a>), osteomyelitis of the jaw, and hearing problems because of small auditory canals. X-rays showed diffuse osteosclerosis of the trabecular and cortical bone and osteosclerosis of the skull with enlargement of the cranial vault. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12015390+12579474+11701785+1002767+10434540" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0016" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 ENDOSTEAL HYPEROSTOSIS, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, ALA214THR
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908671 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908671;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006663 OR RCV000786921 OR RCV005229766" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006663, RCV000786921, RCV005229766" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006663...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family from Portland, Oregon (kindred C) with autosomal dominant endosteal hyperostosis (<a href="/entry/144750">144750</a>), originally described by <a href="#2" class="mim-tip-reference" title="Beals, R. K., McLoughlin, S. W., Teed, R. L., McDonald, C. <strong>Dominant endosteal hyperostosis: skeletal characteristics and review of the literature.</strong> J. Bone Joint Surg. Am. 83: 1643-1649, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11701785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11701785</a>]" pmid="11701785">Beals et al. (2001)</a>, <a href="#36" class="mim-tip-reference" title="Van Wesenbeeck, L., Cleiren, E., Gram, J., Beals, R. K., Benichou, O., Scopelliti, D., Key, L., Renton, T., Bartels, C., Gong, Y., Warman, M. L., de Vernejoul, M.-C., Bollerslev, J., Van Hul, W. <strong>Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density.</strong> Am. J. Hum. Genet. 72: 763-771, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12579474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12579474</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12579474[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/368277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12579474">Van Wesenbeeck et al. (2003)</a> found a 640G-A transition in exon 3 of the LRP5 gene, resulting in an ala214-to-thr (A214T) mutation. A different mutation involving the same codon (A214V; <a href="#0017">603506.0017</a>) was identified in another family (kindred E) diagnosed with a similar phenotype of increased bone density. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12579474+11701785" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0017" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 ENDOSTEAL HYPEROSTOSIS, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, ALA214VAL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908672 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908672;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006664" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006664" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006664</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Van Wesenbeeck, L., Cleiren, E., Gram, J., Beals, R. K., Benichou, O., Scopelliti, D., Key, L., Renton, T., Bartels, C., Gong, Y., Warman, M. L., de Vernejoul, M.-C., Bollerslev, J., Van Hul, W. <strong>Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density.</strong> Am. J. Hum. Genet. 72: 763-771, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12579474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12579474</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12579474[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/368277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12579474">Van Wesenbeeck et al. (2003)</a> identified a 641C-T transition in exon 3 of the LRP5 gene, resulting in an ala214-to-val (A214V) mutation, in a previously described family of English origin (kindred E; <a href="#28" class="mim-tip-reference" title="Renton,T., Odell, E., Drage, N. A. <strong>Differential diagnosis and treatment of autosomal dominant osteosclerosis of the mandible.</strong> Brit. J. Oral Maxillofac. Surg. 40: 55-59, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11883972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11883972</a>] [<a href="https://doi.org/10.1054/bjom.2001.0719" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11883972">Renton et al., 2002</a>) with endosteal hyperostosis (<a href="/entry/144750">144750</a>), reported as autosomal dominant osteosclerosis manifest by an enlarged mandible (present in the 20-year-old proband and her father), increased gonial angle, and thickened cortical bone. In the father, there were no other clinical signs and the radiographic appearance of the skull was within normal limits. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11883972+12579474" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0018" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 OSTEOPETROSIS, AUTOSOMAL DOMINANT 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, THR253ILE
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908673 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908673;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908673" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908673" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006665" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006665" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006665</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Van Wesenbeeck, L., Cleiren, E., Gram, J., Beals, R. K., Benichou, O., Scopelliti, D., Key, L., Renton, T., Bartels, C., Gong, Y., Warman, M. L., de Vernejoul, M.-C., Bollerslev, J., Van Hul, W. <strong>Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density.</strong> Am. J. Hum. Genet. 72: 763-771, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12579474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12579474</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12579474[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/368277" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12579474">Van Wesenbeeck et al. (2003)</a> identified a 758C-T transition in exon 4 of the LRP5 gene, resulting in a thr253-to-ile (T253I) substitution, in 2 previously described and presumably unrelated Danish families (kindreds I and J; <a href="#35" class="mim-tip-reference" title="Van Hul, E., Gram, J., Bollerslev, J., Van Wesenbeeck, L., Mathysen, E., Andersen, P. E., Vanhoenacker, F., Van Hul, W. <strong>Localization of the gene causing autosomal dominant osteopetrosis type I to chromosome 11q12-13.</strong> J. Bone Miner. Res. 17: 1111-1117, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12054167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12054167</a>] [<a href="https://doi.org/10.1359/jbmr.2002.17.6.1111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12054167">Van Hul et al., 2002</a>) diagnosed with autosomal dominant osteopetrosis type I (OPTA1; <a href="/entry/607634">607634</a>). In both families, which originated from the same county in Denmark, affected members showed generalized osteosclerosis, most pronounced in the cranial vault, not associated with an increased fracture rate. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12054167+12579474" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0019" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 BONE MINERAL DENSITY QUANTITATIVE TRAIT LOCUS 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, 2220C-T
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs2306862 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2306862;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs2306862?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2306862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2306862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006666 OR RCV000173754 OR RCV000712233 OR RCV002277337 OR RCV002277338" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006666, RCV000173754, RCV000712233, RCV002277337, RCV002277338" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006666...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In adult Japanese women, <a href="#23" class="mim-tip-reference" title="Mizuguchi, T., Furuta, I., Watanabe, Y., Tsukamoto, K., Tomita, H., Tsujihata, M., Ohta, T., Kishino, T., Matsumoto, N., Minakami, H., Niikawa, N., Yoshiura, K. <strong>LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant for bone mineral density.</strong> J. Hum. Genet. 49: 80-86, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14727154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14727154</a>] [<a href="https://doi.org/10.1007/s10038-003-0111-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14727154">Mizuguchi et al. (2004)</a> found an association between the T allele of the 2220C-T polymorphism in exon 10 of the LRP5 gene and low bone mineral density (BMND1; <a href="/entry/601884">601884</a>). A case-control study of 126 women with osteoporosis (see <a href="/entry/166710">166710</a>) and 131 normal controls revealed a significant difference in allelic frequency of the 2220C-T SNP (p = 0.009). The authors suggested that LRP5 is a BMD determinant and contributes to a risk of osteoporosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14727154" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0020" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 EXUDATIVE VITREORETINOPATHY 4, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, IVS21DS, T-G, +2
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs80358322 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358322;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs80358322?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80358322" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80358322" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006667 OR RCV000489366 OR RCV000505032 OR RCV001267021 OR RCV004795379 OR RCV004814845 OR RCV004821259" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006667, RCV000489366, RCV000505032, RCV001267021, RCV004795379, RCV004814845, RCV004821259" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006667...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with autosomal dominant exudative vitreoretinopathy (EVR4; <a href="/entry/601813">601813</a>) reported by <a href="#25" class="mim-tip-reference" title="Price, S. M., Periam, N., Humphries, A., Woodruff, G., Trembath, R. C. <strong>Familial exudative vitreoretinopathy linked to D11S533 in a large Asian family with consanguinity.</strong> Ophthalmic Genet. 17: 53-57, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8832721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8832721</a>] [<a href="https://doi.org/10.3109/13816819609057871" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8832721">Price et al. (1996)</a>, <a href="#32" class="mim-tip-reference" title="Toomes, C., Bottomley, H. M., Jackson, R. M., Towns, K. V., Scott, S., Mackey, D. A., Craig, J. E., Jiang, L., Yang, Z., Trembath, R., Woodruff, G., Gregory-Evans, C. Y., Gregory-Evans, K., Parker, M. J., Black, G. C. M., Downey, L. M., Zhang, K., Inglehearn, C. F. <strong>Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q.</strong> Am. J. Hum. Genet. 74: 721-730, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15024691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15024691</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15024691[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/383202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15024691">Toomes et al. (2004)</a> identified a heterozygous substitution of the second nucleotide of intron 21 of the LRP5 gene, changing the GT splice donor site to GG (4488+2T-G). The mutation was predicted to lead to deletion of exon 21, resulting in a frameshift at codon 1449 with a premature stop codon following 52 incorrect amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8832721+15024691" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0021" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 EXUDATIVE VITREORETINOPATHY 4, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, 1-BP INS, 4119C
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80358321 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358321;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80358321" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80358321" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006668 OR RCV005089194" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006668, RCV005089194" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006668...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of an American family with autosomal dominant exudative vitreoretinopathy (EVR4; <a href="/entry/601813">601813</a>), <a href="#32" class="mim-tip-reference" title="Toomes, C., Bottomley, H. M., Jackson, R. M., Towns, K. V., Scott, S., Mackey, D. A., Craig, J. E., Jiang, L., Yang, Z., Trembath, R., Woodruff, G., Gregory-Evans, C. Y., Gregory-Evans, K., Parker, M. J., Black, G. C. M., Downey, L. M., Zhang, K., Inglehearn, C. F. <strong>Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q.</strong> Am. J. Hum. Genet. 74: 721-730, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15024691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15024691</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15024691[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/383202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15024691">Toomes et al. (2004)</a> identified a heterozygous 1-bp insertion in exon 20 of the LRP5 gene, 4119insC, resulting in a frameshift at codon 1374 with a premature stop codon following 175 incorrect amino acids. Two asymptomatic members carried the mutation but had not been examined by fluorescein angiography to exclude a very mild phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15024691" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0022" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 EXUDATIVE VITREORETINOPATHY 4, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, ARG570GLN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80358312 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358312;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80358312" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80358312" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006669 OR RCV000623689 OR RCV003555944 OR RCV004814846" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006669, RCV000623689, RCV003555944, RCV004814846" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006669...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family reported by <a href="#10" class="mim-tip-reference" title="de Crecchio, G., Simonelli, F., Nunziata, G., Mazzeo, S., Greco, G. M., Rinaldi, E., Ventruto, V., Ciccodicola, A., Miano, M. G., Testa, F., Curci, A., D'Urso, M. M., Rinaldi, M. M., Cavaliere, M. L., Castelluccio, P. <strong>Autosomal recessive familial exudative vitreoretinopathy: evidence for genetic heterogeneity.</strong> Clin. Genet. 54: 315-320, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9831343/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9831343</a>] [<a href="https://doi.org/10.1034/j.1399-0004.1998.5440409.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9831343">de Crecchio et al. (1998)</a>, <a href="#17" class="mim-tip-reference" title="Jiao, X., Ventruto, V., Trese, M. T., Shastry, B. S., Hejtmancik, J. F. <strong>Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5.</strong> Am. J. Hum. Genet. 75: 878-884, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15346351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15346351</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15346351[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/425080" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15346351">Jiao et al. (2004)</a> found that sisters with exudative vitreoretinopathy (EVR4; <a href="/entry/601813">601813</a>) carried a homozygous 1757G-A transition in 8 of the LRP5 gene, resulting in an arg570-to-gln (R570Q) amino acid substitution. The sisters were diagnosed at ages 5 years and 7 years and had shown typical signs of FEVR. They required multiple procedures including photocoagulation, cryopexy, and vitrectomy. They showed no signs of systemic disease, including fractures, at ages 29 years and 31 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9831343+15346351" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0023" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 EXUDATIVE VITREORETINOPATHY 4, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, ARG752GLY
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908674 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908674;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908674" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121908674" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006670 OR RCV002512844" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006670, RCV002512844" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006670...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with autosomal recessive exudative vitreoretinopathy (EVR4; <a href="/entry/601813">601813</a>) reported by <a href="#31" class="mim-tip-reference" title="Shastry, B. S., Trese, M. T. <strong>Familial exudative vitreoretinopathy: further evidence for genetic heterogeneity. (Letter)</strong> Am. J. Med. Genet. 69: 217-218, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9056564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9056564</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19970317)69:2<217::aid-ajmg19>3.0.co;2-o" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9056564">Shastry and Trese (1997)</a>, <a href="#17" class="mim-tip-reference" title="Jiao, X., Ventruto, V., Trese, M. T., Shastry, B. S., Hejtmancik, J. F. <strong>Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5.</strong> Am. J. Hum. Genet. 75: 878-884, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15346351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15346351</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15346351[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/425080" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15346351">Jiao et al. (2004)</a> identified a homozygous 2302C-G transversion in exon 10 of the LRP5 gene, resulting in an arg752-to-gly (R752G) amino acid change in the third YWTD domain of the protein. Two affected sisters also had an affected paternal uncle; these 3 affected individuals were the offspring of consanguineous marriages. Both sisters were diagnosed at 3 years of age, at which time they manifested typical signs of FEVR, including large retinal folds, peripheral traction and exudates, and an avascular demarcation line near the equator and vitreous detachments. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9056564+15346351" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0024" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0024 EXUDATIVE VITREORETINOPATHY 4, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, GLU1367LYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28939709 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28939709;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs28939709?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28939709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28939709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006671 OR RCV004814847" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006671, RCV004814847" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006671...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a brother and sister with familial exudative retinopathy (EVR4; <a href="/entry/601813">601813</a>) reported by <a href="#10" class="mim-tip-reference" title="de Crecchio, G., Simonelli, F., Nunziata, G., Mazzeo, S., Greco, G. M., Rinaldi, E., Ventruto, V., Ciccodicola, A., Miano, M. G., Testa, F., Curci, A., D'Urso, M. M., Rinaldi, M. M., Cavaliere, M. L., Castelluccio, P. <strong>Autosomal recessive familial exudative vitreoretinopathy: evidence for genetic heterogeneity.</strong> Clin. Genet. 54: 315-320, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9831343/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9831343</a>] [<a href="https://doi.org/10.1034/j.1399-0004.1998.5440409.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9831343">de Crecchio et al. (1998)</a>, <a href="#17" class="mim-tip-reference" title="Jiao, X., Ventruto, V., Trese, M. T., Shastry, B. S., Hejtmancik, J. F. <strong>Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5.</strong> Am. J. Hum. Genet. 75: 878-884, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15346351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15346351</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15346351[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/425080" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15346351">Jiao et al. (2004)</a> found a homozygous 414G-A transition in exon 19 of the LRP5 gene, resulting in a glu1367-to-lys (E1367K) amino acid change. The brother and sister were diagnosed with retinal detachments at ages 6 years and 8 years, respectively, and also showed other typical signs of FEVR. They showed no systemic symptoms, such as fractures or traumatic injuries, by ages 12 years and 10 years, respectively. No additional family members were known to be affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9831343+15346351" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0025" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0025 EXUDATIVE VITREORETINOPATHY 4, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, LEU145PHE
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80358305 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358305;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80358305" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80358305" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006672 OR RCV000033256" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006672, RCV000033256" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006672...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 Japanese sibs with exudative vitreoretinopathy-4 (EVR4; <a href="/entry/601813">601813</a>), <a href="#26" class="mim-tip-reference" title="Qin, M., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K., Kondo, H. <strong>Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes.</strong> Hum. Mutat. 26: 104-112, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15981244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15981244</a>] [<a href="https://doi.org/10.1002/humu.20191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15981244">Qin et al. (2005)</a> identified a heterozygous 433C-T transition in exon 2 of the LRP5 gene, resulting in a leu145-to-phe (L145F) substitution in a conserved residue in the beta-propeller structure of the protein. The mother, who also carried the mutation, had mild retinal avascularization and significantly decreased bone mineral density (z score of -2.5). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15981244" 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 23-year-old Japanese man with pseudoglioma and multiple fractures due to osteopenia (OPPG; <a href="/entry/259770">259770</a>), <a href="#24" class="mim-tip-reference" title="Narumi, S., Numakura, C., Shiihara, T., Seiwa, C., Nozaki, Y., Yamagata, T., Momoi, M. Y., Watanabe, Y., Yoshino, M., Matsuishi, T., Nishi, E., Kawame, H., Akahane, T., Nishimura, G., Emi, M., Hasegawa, T. <strong>Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma syndrome: identification of a 7.2-kb microdeletion using oligonucleotide tiling microarray.</strong> Am. J. Med. Genet. 152A: 133-140, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20034086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20034086</a>] [<a href="https://doi.org/10.1002/ajmg.a.33177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20034086">Narumi et al. (2010)</a> identified compound heterozygosity for the L145F mutation and a 1655T-C transition in the LRP5 gene, resulting in a thr552-to-met (T552M; <a href="#0029">603506.0029</a>) substitution at a highly conserved residue in the second YWTD-EGF-like domain. The patient, who had normal intelligence, had microphthalmia and retinal detachment in the left eye and persistent hyperplasia of the primary vitreous in the right eye. Radiography revealed osteopenia, kyphoscoliosis, and platyspondyly in all vertebrae; he became wheelchair-dependent at 11 years of age due to multiple compression fractures. His unaffected mother was heterozygous for L145F; DNA was unavailable from his father. Neither mutation was found in 100 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20034086" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0026" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0026 EXUDATIVE VITREORETINOPATHY 4, DIGENIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, ARG444CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs80358308 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358308;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs80358308?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80358308" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80358308" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006673 OR RCV001376975 OR RCV004742221" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006673, RCV001376975, RCV004742221" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006673...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a Japanese family with exudative vitreoretinopathy-4 (EVR4; <a href="/entry/601813">601813</a>), <a href="#26" class="mim-tip-reference" title="Qin, M., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K., Kondo, H. <strong>Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes.</strong> Hum. Mutat. 26: 104-112, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15981244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15981244</a>] [<a href="https://doi.org/10.1002/humu.20191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15981244">Qin et al. (2005)</a> identified a heterozygous 1330C-T transition in exon 6 of the LRP5 gene, resulting in an arg444-to-cys (R444C) substitution in a conserved residue in the beta-propeller structure of the protein. Affected members of this family also had a heterozygous mutation in the FZD4 gene (R417Q; <a href="/entry/604579#0003">604579.0003</a>; <a href="#19" class="mim-tip-reference" title="Kondo, H., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K. <strong>Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity.</strong> Brit. J. Ophthal. 87: 1291-1295, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14507768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14507768</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14507768[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/bjo.87.10.1291" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14507768">Kondo et al., 2003</a>). The 2 mutations cosegregated in the family, indicating that both mutations were located on the same chromosomes consistent with digenic inheritance. The ocular phenotype in this family tended to be more severe compared to that seen in a family with the FZD4 R417Q mutation alone (<a href="#19" class="mim-tip-reference" title="Kondo, H., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K. <strong>Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity.</strong> Brit. J. Ophthal. 87: 1291-1295, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14507768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14507768</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14507768[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/bjo.87.10.1291" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14507768">Kondo et al., 2003</a>). In addition, the proband in the family with both mutations had reduced bone mass (z score of -2.1), whereas the proband carrying the FZD4 mutation alone had a normal bone mineral density. <a href="#26" class="mim-tip-reference" title="Qin, M., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K., Kondo, H. <strong>Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes.</strong> Hum. Mutat. 26: 104-112, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15981244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15981244</a>] [<a href="https://doi.org/10.1002/humu.20191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15981244">Qin et al. (2005)</a> concluded that the 2 mutations showed a synergistic deleterious effect in this family. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14507768+15981244" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0027" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0027 EXUDATIVE VITREORETINOPATHY 4, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, GLY610ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs80358313 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358313;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs80358313?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80358313" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80358313" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006674 OR RCV001579335 OR RCV004814848" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006674, RCV001579335, RCV004814848" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006674...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese girl with exudative vitreoretinopathy-4 (EVR4; <a href="/entry/601813">601813</a>), <a href="#26" class="mim-tip-reference" title="Qin, M., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K., Kondo, H. <strong>Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes.</strong> Hum. Mutat. 26: 104-112, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15981244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15981244</a>] [<a href="https://doi.org/10.1002/humu.20191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15981244">Qin et al. (2005)</a> identified compound heterozygosity for 2 mutations in the LRP5 gene: a 1828G-A transition in exon 9, resulting in a gly610-to-arg (G610R) substitution, and a 10-bp deletion (del803-812; <a href="#0028">603506.0028</a>) in exon 4. Each parent was heterozygous for 1 of the mutations. Although neither parent had the ocular phenotype, both showed decreased bone mineral densities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15981244" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0028" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0028 EXUDATIVE VITREORETINOPATHY 4, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, 10-BP DEL, NT803
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80358307 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358307;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80358307" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80358307" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006675" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006675" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006675</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 10-bp deletion in the LRP5 gene (del803-812) that was found in compound heterozygous state in a patient with exudative vitreoretinopathy-4 (EVR4; <a href="/entry/601813">601813</a>) by <a href="#26" class="mim-tip-reference" title="Qin, M., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K., Kondo, H. <strong>Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes.</strong> Hum. Mutat. 26: 104-112, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15981244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15981244</a>] [<a href="https://doi.org/10.1002/humu.20191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15981244">Qin et al. (2005)</a>, see <a href="#0027">603506.0027</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15981244" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0029" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0029 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, THR552MET
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397514663 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514663;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs397514663" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs397514663" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000033257 OR RCV003556102" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000033257, RCV003556102" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000033257...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the thr552-to-met (T552M) mutation in the LRP5 gene that was found in compound heterozygous state in a patient with pseudoglioma and multiple fractures due to osteopenia (OPPG; <a href="/entry/259770">259770</a>) by <a href="#24" class="mim-tip-reference" title="Narumi, S., Numakura, C., Shiihara, T., Seiwa, C., Nozaki, Y., Yamagata, T., Momoi, M. Y., Watanabe, Y., Yoshino, M., Matsuishi, T., Nishi, E., Kawame, H., Akahane, T., Nishimura, G., Emi, M., Hasegawa, T. <strong>Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma syndrome: identification of a 7.2-kb microdeletion using oligonucleotide tiling microarray.</strong> Am. J. Med. Genet. 152A: 133-140, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20034086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20034086</a>] [<a href="https://doi.org/10.1002/ajmg.a.33177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20034086">Narumi et al. (2010)</a>, see <a href="#0025">603506.0025</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20034086" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0030" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0030 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, PRO382LEU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs397514664 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514664;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs397514664?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs397514664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs397514664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000033258 OR RCV001380061" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000033258, RCV001380061" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000033258...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 18-year-old Japanese male and a 10-year-old Japanese boy with osteoporosis-pseudoglioma syndrome (OPPG; <a href="/entry/259770">259770</a>), <a href="#24" class="mim-tip-reference" title="Narumi, S., Numakura, C., Shiihara, T., Seiwa, C., Nozaki, Y., Yamagata, T., Momoi, M. Y., Watanabe, Y., Yoshino, M., Matsuishi, T., Nishi, E., Kawame, H., Akahane, T., Nishimura, G., Emi, M., Hasegawa, T. <strong>Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma syndrome: identification of a 7.2-kb microdeletion using oligonucleotide tiling microarray.</strong> Am. J. Med. Genet. 152A: 133-140, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20034086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20034086</a>] [<a href="https://doi.org/10.1002/ajmg.a.33177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20034086">Narumi et al. (2010)</a> identified compound heterozygosity for a 1145C-T transition in the LRP5 gene, resulting in a pro382-to-leu (P382L) substitution at a highly conserved residue in the second YWTD-EGF-like domain, and another LRP5 mutation. The 18-year-old also carried a 731C-T transition, resulting in a thr244-to-met (T244M; <a href="#0031">603506.0031</a>) substitution at a highly conserved residue in the first YWTD-EGF-like domain; the 10-year-old carried a 4600C-T transition, resulting in an arg1534-to-ter (R1534X; <a href="#0032">603506.0032</a>) substitution in the cytoplasmic domain. In both families, the unaffected parents were each heterozygous for 1 of the mutations, none of which was found in 100 controls. In addition to their eye and bone findings, both patients had moderate mental retardation. <a href="#24" class="mim-tip-reference" title="Narumi, S., Numakura, C., Shiihara, T., Seiwa, C., Nozaki, Y., Yamagata, T., Momoi, M. Y., Watanabe, Y., Yoshino, M., Matsuishi, T., Nishi, E., Kawame, H., Akahane, T., Nishimura, G., Emi, M., Hasegawa, T. <strong>Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma syndrome: identification of a 7.2-kb microdeletion using oligonucleotide tiling microarray.</strong> Am. J. Med. Genet. 152A: 133-140, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20034086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20034086</a>] [<a href="https://doi.org/10.1002/ajmg.a.33177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20034086">Narumi et al. (2010)</a> noted that the T244M and R1534X mutations had previously been reported in OPPG patients by <a href="#1" class="mim-tip-reference" title="Ai, M., Heeger, S., Bartels, C. F., Schelling, D. K., Osteoporosis-Pseudoglioma Collaborative Group. <strong>Clinical and molecular findings in osteoporosis-pseudoglioma syndrome.</strong> Am. J. Hum. Genet. 77: 741-753, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16252235/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16252235</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16252235[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/497706" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16252235">Ai et al. (2005)</a> and <a href="#14" class="mim-tip-reference" title="Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., Zacharin, M., Oexle, K., and 50 others. <strong>LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.</strong> Cell 107: 513-523, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11719191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11719191</a>] [<a href="https://doi.org/10.1016/s0092-8674(01)00571-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11719191">Gong et al. (2001)</a>, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11719191+20034086+16252235" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0031" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0031 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, THR244MET
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs397514665 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514665;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs397514665?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs397514665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs397514665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000033259" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000033259" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000033259</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the thr244-to-met (T244M) mutation in the LRP5 gene that was found in compound heterozygous state in a patient with osteoporosis-pseudoglioma syndrome (OPPG; <a href="/entry/259770">259770</a>) by <a href="#24" class="mim-tip-reference" title="Narumi, S., Numakura, C., Shiihara, T., Seiwa, C., Nozaki, Y., Yamagata, T., Momoi, M. Y., Watanabe, Y., Yoshino, M., Matsuishi, T., Nishi, E., Kawame, H., Akahane, T., Nishimura, G., Emi, M., Hasegawa, T. <strong>Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma syndrome: identification of a 7.2-kb microdeletion using oligonucleotide tiling microarray.</strong> Am. J. Med. Genet. 152A: 133-140, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20034086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20034086</a>] [<a href="https://doi.org/10.1002/ajmg.a.33177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20034086">Narumi et al. (2010)</a>, see <a href="#0030">603506.0030</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20034086" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0032" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0032 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, ARG1534TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs149645175 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs149645175;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs149645175?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs149645175" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs149645175" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000033260" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000033260" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000033260</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg1534-to-ter (R1534X) mutation in the LRP5 gene that was found in compound heterozygous state in a patient with osteoporosis-pseudoglioma syndrome (OPPG; <a href="/entry/259770">259770</a>) by <a href="#24" class="mim-tip-reference" title="Narumi, S., Numakura, C., Shiihara, T., Seiwa, C., Nozaki, Y., Yamagata, T., Momoi, M. Y., Watanabe, Y., Yoshino, M., Matsuishi, T., Nishi, E., Kawame, H., Akahane, T., Nishimura, G., Emi, M., Hasegawa, T. <strong>Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma syndrome: identification of a 7.2-kb microdeletion using oligonucleotide tiling microarray.</strong> Am. J. Med. Genet. 152A: 133-140, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20034086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20034086</a>] [<a href="https://doi.org/10.1002/ajmg.a.33177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20034086">Narumi et al. (2010)</a>, see <a href="#0030">603506.0030</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20034086" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0033" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0033 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, IVS7, G-A, +1
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1554967176 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1554967176;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1554967176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1554967176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000033261" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000033261" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000033261</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-year-old Japanese boy with osteoporosis-pseudoglioma syndrome (OPPG; <a href="/entry/259770">259770</a>), <a href="#24" class="mim-tip-reference" title="Narumi, S., Numakura, C., Shiihara, T., Seiwa, C., Nozaki, Y., Yamagata, T., Momoi, M. Y., Watanabe, Y., Yoshino, M., Matsuishi, T., Nishi, E., Kawame, H., Akahane, T., Nishimura, G., Emi, M., Hasegawa, T. <strong>Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma syndrome: identification of a 7.2-kb microdeletion using oligonucleotide tiling microarray.</strong> Am. J. Med. Genet. 152A: 133-140, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20034086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20034086</a>] [<a href="https://doi.org/10.1002/ajmg.a.33177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20034086">Narumi et al. (2010)</a> identified compound heterozygosity for a splice site transition (1584+1G-A) in intron 7 and a 7.2-kb microdeletion encompassing exons 22 and 23 (<a href="#0034">603506.0034</a>) of the LRP5 gene. The unaffected parents were each heterozygous for 1 of the mutations, neither of which was found in 100 controls. Sequencing of a mutant RT-PCR fragment indicated that the splice site mutation caused cryptic splice donor site utilization 63-bp downstream of the native exon/intron junction, predicted to add an extra 21 amino acids without a termination codon after glu528 (E528_V529ins21). The 7.2-kb microdeletion was discovered using custom-designed oligonucleotide tiling array CGH targeted to a 600-kb genomic region harboring LRP5; <a href="#24" class="mim-tip-reference" title="Narumi, S., Numakura, C., Shiihara, T., Seiwa, C., Nozaki, Y., Yamagata, T., Momoi, M. Y., Watanabe, Y., Yoshino, M., Matsuishi, T., Nishi, E., Kawame, H., Akahane, T., Nishimura, G., Emi, M., Hasegawa, T. <strong>Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma syndrome: identification of a 7.2-kb microdeletion using oligonucleotide tiling microarray.</strong> Am. J. Med. Genet. 152A: 133-140, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20034086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20034086</a>] [<a href="https://doi.org/10.1002/ajmg.a.33177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20034086">Narumi et al. (2010)</a> stated that this was one of the smallest deletions identified by aCGH-based analyses. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20034086" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0034" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0034 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, 7.2-KB DEL, EXONS 22-23
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000033262" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000033262" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000033262</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 7.2-kb microdeletion encompassing exons 22 and 23 of the LRP5 gene that was found in compound heterozygous state in a patient with osteoporosis-pseudoglioma syndrome (OPPG; <a href="/entry/259770">259770</a>) by <a href="#24" class="mim-tip-reference" title="Narumi, S., Numakura, C., Shiihara, T., Seiwa, C., Nozaki, Y., Yamagata, T., Momoi, M. Y., Watanabe, Y., Yoshino, M., Matsuishi, T., Nishi, E., Kawame, H., Akahane, T., Nishimura, G., Emi, M., Hasegawa, T. <strong>Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma syndrome: identification of a 7.2-kb microdeletion using oligonucleotide tiling microarray.</strong> Am. J. Med. Genet. 152A: 133-140, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20034086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20034086</a>] [<a href="https://doi.org/10.1002/ajmg.a.33177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20034086">Narumi et al. (2010)</a>, see <a href="#0033">603506.0033</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20034086" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0035" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0035 POLYCYSTIC LIVER DISEASE 4 WITH OR WITHOUT KIDNEY CYSTS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, ARG1188TRP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs141178995 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs141178995;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs141178995?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs141178995" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs141178995" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000149786 OR RCV000584769 OR RCV002516009 OR RCV005003492" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000149786, RCV000584769, RCV002516009, RCV005003492" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000149786...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 19 affected individuals from a large multigenerational Dutch family with polycystic liver disease-4 with or without kidney cysts (PCLD4; <a href="/entry/617875">617875</a>), <a href="#8" class="mim-tip-reference" title="Cnossen, W. R., te Morsche, R. H. M., Hoischen, A., Gilissen, C., Chrispijn, M., Venselaar, H., Mehdi, S., Bergmann, C., Veltman, J. A., Drenth, J. P. H. <strong>Whole-exome sequencing reveals LRP5 mutations and canonical Wnt signaling associated with hepatic cystogenesis.</strong> Proc. Nat. Acad. Sci. 111: 5343-5348, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24706814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24706814</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24706814[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1309438111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24706814">Cnossen et al. (2014)</a> identified a heterozygous c.3562C-T transition in the LRP5 gene, resulting in an arg1188-to-trp (R1188W) substitution at a highly conserved residue in the extracellular domain that was predicted to disrupt a beta-propeller domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the 1000 Genomes Project or Exome Sequencing Project databases or in 2,300 in-house controls. The findings were also confirmed by linkage analysis. There were a few younger unaffected carriers, suggesting age-related incomplete penetrance. Liver tissue from the proband showed intense LRP5 immunostaining of cyst-lining epithelium and bile ducts. In vitro functional expression studies showed that the variant resulted in decreased WNT (see, e.g., <a href="/entry/164820">164820</a>) signaling activation in response to Wnt3a (<a href="/entry/606359">606359</a>) compared to wildtype, as well as altered expression of some target genes in this pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24706814" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0036" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0036 POLYCYSTIC LIVER DISEASE 4 WITH OR WITHOUT KIDNEY CYSTS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, VAL454MET
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs373910016 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs373910016;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs373910016?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs373910016" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs373910016" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000162092 OR RCV000584798 OR RCV002277318 OR RCV002515121 OR RCV004815255 OR RCV005049440" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000162092, RCV000584798, RCV002277318, RCV002515121, RCV004815255, RCV005049440" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000162092...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 86-year-old Dutch woman and her 49-year-old daughter with polycystic liver disease-4 with or without kidney cysts (PCLD4; <a href="/entry/617875">617875</a>), <a href="#8" class="mim-tip-reference" title="Cnossen, W. R., te Morsche, R. H. M., Hoischen, A., Gilissen, C., Chrispijn, M., Venselaar, H., Mehdi, S., Bergmann, C., Veltman, J. A., Drenth, J. P. H. <strong>Whole-exome sequencing reveals LRP5 mutations and canonical Wnt signaling associated with hepatic cystogenesis.</strong> Proc. Nat. Acad. Sci. 111: 5343-5348, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24706814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24706814</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24706814[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1309438111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24706814">Cnossen et al. (2014)</a> identified a heterozygous c.1360G-A transition in the LRP5 gene, resulting in a val454-to-met (V454M) substitution at a highly conserved residue in the extracellular domain. The mutation was found by direct sequencing of the LRP5 gene in a cohort of 150 probands with cystic liver disease; it was not found in online exome sequencing databases, in in-house samples, or in 1,000 Dutch controls. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24706814" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0037" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0037 POLYCYSTIC LIVER DISEASE 4 WITHOUT KIDNEY CYSTS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, ARG1529SER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs724159826 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs724159826;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs724159826?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs724159826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs724159826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000149787 OR RCV000584817" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000149787, RCV000584817" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000149787...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Moroccan woman and her 2 adult daughters with polycystic liver disease-4 without kidney cysts (PCLD4; <a href="/entry/617875">617875</a>), <a href="#8" class="mim-tip-reference" title="Cnossen, W. R., te Morsche, R. H. M., Hoischen, A., Gilissen, C., Chrispijn, M., Venselaar, H., Mehdi, S., Bergmann, C., Veltman, J. A., Drenth, J. P. H. <strong>Whole-exome sequencing reveals LRP5 mutations and canonical Wnt signaling associated with hepatic cystogenesis.</strong> Proc. Nat. Acad. Sci. 111: 5343-5348, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24706814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24706814</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24706814[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1309438111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24706814">Cnossen et al. (2014)</a> identified a heterozygous c.4587G-C transversion in the LRP5 gene, resulting in an arg1529-to-ser (R1529S) substitution at a highly conserved residue in the intracellular domain. The mutation was found by direct sequencing of the LRP5 gene in a cohort of 150 probands with cystic liver disease; it was not found in online exome sequencing databases, in in-house samples, or in 525 Moroccan controls. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24706814" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0038" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0038 POLYCYSTIC LIVER DISEASE 4 WITH KIDNEY CYSTS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LRP5, ASP1551ASN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs724159827 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs724159827;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs724159827?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs724159827" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs724159827" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000149788 OR RCV000584765 OR RCV005008056 OR RCV005089721" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000149788, RCV000584765, RCV005008056, RCV005089721" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000149788...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 65-year-old Dutch man with polycystic liver disease-4 with kidney cysts (PCLD4; <a href="/entry/617875">617875</a>), <a href="#8" class="mim-tip-reference" title="Cnossen, W. R., te Morsche, R. H. M., Hoischen, A., Gilissen, C., Chrispijn, M., Venselaar, H., Mehdi, S., Bergmann, C., Veltman, J. A., Drenth, J. P. H. <strong>Whole-exome sequencing reveals LRP5 mutations and canonical Wnt signaling associated with hepatic cystogenesis.</strong> Proc. Nat. Acad. Sci. 111: 5343-5348, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24706814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24706814</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24706814[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1309438111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24706814">Cnossen et al. (2014)</a> identified a heterozygous c.4651G-A transition in the LRP5 gene, resulting in an asp1551-to-asn (D1551N) substitution at a highly conserved residue in the intracellular domain. The mutation was found by direct sequencing of the LRP5 gene in a cohort of 150 probands with cystic liver disease; it was not found in online exome sequencing databases, in in-house samples, or in 1,000 Dutch controls. The patient had no family history of the disorder. In vitro functional expression studies showed that the variant resulted in decreased WNT (see, e.g., <a href="/entry/164820">164820</a>) signaling activation in response to Wnt3a (<a href="/entry/606359">606359</a>) compared to wildtype, as well as altered expression of some target genes in this pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24706814" 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>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</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="Ai2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ai, M., Heeger, S., Bartels, C. F., Schelling, D. K., Osteoporosis-Pseudoglioma Collaborative Group.
|
|
<strong>Clinical and molecular findings in osteoporosis-pseudoglioma syndrome.</strong>
|
|
Am. J. Hum. Genet. 77: 741-753, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16252235/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16252235</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16252235[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16252235" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/497706" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Beals2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Beals, R. K., McLoughlin, S. W., Teed, R. L., McDonald, C.
|
|
<strong>Dominant endosteal hyperostosis: skeletal characteristics and review of the literature.</strong>
|
|
J. Bone Joint Surg. Am. 83: 1643-1649, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11701785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11701785</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11701785" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Beals1976" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Beals, R. K.
|
|
<strong>Endosteal hyperostosis.</strong>
|
|
J. Bone Joint Surg. Am. 58: 1172-1173, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1002767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1002767</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1002767" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Benson1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Benson, W. E.
|
|
<strong>Familial exudative vitreoretinopathy.</strong>
|
|
Trans. Am. Ophthal. Soc. 93: 473-521, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8719692/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8719692</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8719692" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Boyden2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Boyden, L. M., Mao, J., Belsky, J., Mitzner, L., Farhi, A., Mitnick, M. A., Wu, D., Insogna, K., Lifton, R. P.
|
|
<strong>High bone density due to a mutation in LDL-receptor-related protein 5.</strong>
|
|
New Eng. J. Med. 346: 1513-1521, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12015390/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12015390</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12015390" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMoa013444" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Chen1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, D., Lathrop, W., Dong, Y.
|
|
<strong>Molecular cloning of mouse Lrp7(Lr3) cDNA and chromosomal mapping of orthologous genes in mouse and human.</strong>
|
|
Genomics 55: 314-321, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10049586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10049586</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10049586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1998.5688" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Clement-Lacroix2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Clement-Lacroix, P., Ai, M., Morvan, F., Roman-Roman, S., Vayssiere, B., Belleville, C., Estrera, K., Warman, M. L., Baron, R., Rawadi, G.
|
|
<strong>Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 17406-17411, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16293698/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16293698</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16293698[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16293698" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0505259102" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Cnossen2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cnossen, W. R., te Morsche, R. H. M., Hoischen, A., Gilissen, C., Chrispijn, M., Venselaar, H., Mehdi, S., Bergmann, C., Veltman, J. A., Drenth, J. P. H.
|
|
<strong>Whole-exome sequencing reveals LRP5 mutations and canonical Wnt signaling associated with hepatic cystogenesis.</strong>
|
|
Proc. Nat. Acad. Sci. 111: 5343-5348, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24706814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24706814</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24706814[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24706814" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.1309438111" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Cui2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cui, Y., Niziolek, P. J., MacDonald, B. T., Zylstra, C. R., Alenina, N., Robinson, D. R., Zhong, Z., Matthes, S., Jacobsen, C. M., Conlon, R. A., Brommage, R., Liu, Q., and 11 others.
|
|
<strong>Lrp5 functions in bone to regulate bone mass.</strong>
|
|
Nature Med. 17: 684-691, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21602802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21602802</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21602802[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21602802" 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/nm.2388" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="de Crecchio1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
de Crecchio, G., Simonelli, F., Nunziata, G., Mazzeo, S., Greco, G. M., Rinaldi, E., Ventruto, V., Ciccodicola, A., Miano, M. G., Testa, F., Curci, A., D'Urso, M. M., Rinaldi, M. M., Cavaliere, M. L., Castelluccio, P.
|
|
<strong>Autosomal recessive familial exudative vitreoretinopathy: evidence for genetic heterogeneity.</strong>
|
|
Clin. Genet. 54: 315-320, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9831343/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9831343</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9831343" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1034/j.1399-0004.1998.5440409.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Dong1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dong, Y., Lathrop, W., Weaver, D., Qiu, Q., Cini, J., Bertolini, D., Chen, D.
|
|
<strong>Molecular cloning and characterization of LR3, a novel LDL receptor family protein with mitogenic activity.</strong>
|
|
Biochem. Biophys. Res. Commun. 251: 784-790, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9790987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9790987</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9790987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/bbrc.1998.9545" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Ferrari2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ferrari, S. L., Deutsch, S., Choudhury, U., Chevalley, T., Bonjour, J.-P., Dermitzakis, E. T., Rizzoli, R., Antonarakis, S. E.
|
|
<strong>Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with variation in vertebral bone mass, vertebral bone size, and stature in whites.</strong>
|
|
Am. J. Hum. Genet. 74: 866-875, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15077203/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15077203</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15077203[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15077203" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/420771" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Fujino2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fujino, T., Asaba, H., Kang, M.-J., Ikeda, Y., Sone, H., Takada, S., Kim, D.-H., Ioka, R. X., Ono, M., Tomoyori, H., Okubo, M., Murase, T., and 13 others.
|
|
<strong>Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion.</strong>
|
|
Proc. Nat. Acad. Sci. 100: 229-234, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12509515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12509515</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12509515[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12509515" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0133792100" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Gong2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., Zacharin, M., Oexle, K., and 50 others.
|
|
<strong>LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.</strong>
|
|
Cell 107: 513-523, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11719191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11719191</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11719191" 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/s0092-8674(01)00571-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Guo2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Guo, Y., Xiong, D., Shen, H., Zhao, L., Xiao, P., Guo, Y., Wang, W., Yang, T., Recker, R. R., Deng, H.
|
|
<strong>Polymorphisms of the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with obesity phenotypes in a large family-based association study.</strong>
|
|
J. Med. Genet. 43: 798-803, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16723389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16723389</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16723389[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16723389" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2006.041715" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Hey1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hey, P. J., Twells, R. C. J., Phillips, M. S., Nakagawa, Y., Brown, S. D., Kawaguchi, Y., Cox, R., Xie, G., Dugan, V., Hammond, H., Metzker, M. L., Todd, J. A., Hess, J. F.
|
|
<strong>Cloning of a novel member of the low-density lipoprotein receptor family.</strong>
|
|
Gene 216: 103-111, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9714764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9714764</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9714764" 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/s0378-1119(98)00311-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Jiao2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jiao, X., Ventruto, V., Trese, M. T., Shastry, B. S., Hejtmancik, J. F.
|
|
<strong>Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5.</strong>
|
|
Am. J. Hum. Genet. 75: 878-884, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15346351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15346351</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15346351[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15346351" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/425080" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Kato2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kato, M., Patel, M. S., Levasseur, R., Lobov, I., Chang, B. H.-J., Glass, D. A., II, Hartmann, C., Li, L., Hwang, T.-H., Brayton, C. F., Lang, R. A., Karsenty, G., Chan, L.
|
|
<strong>Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor.</strong>
|
|
J. Cell Biol. 157: 303-314, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11956231/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11956231</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11956231[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11956231" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1083/jcb.200201089" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Kondo2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kondo, H., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K.
|
|
<strong>Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity.</strong>
|
|
Brit. J. Ophthal. 87: 1291-1295, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14507768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14507768</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14507768[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14507768" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/bjo.87.10.1291" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Little2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Little, R. D., Carulli, J. P., Del Mastro, R. G., Dupuis, J., Osborne, M., Folz, C., Manning, S. P., Swain, P. M., Zhao, S.-C., Eustace, B., Lappe, M. M., Spitzer, L., and 23 others.
|
|
<strong>A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait.</strong>
|
|
Am. J. Hum. Genet. 70: 11-19, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11741193/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11741193</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11741193[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11741193" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/338450" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Magoori2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Magoori, K., Kang, M.-J., Ito, M. R., Kakuuchi, H., Ioka, R. X., Kamataki, A., Kim, D.-H., Asaba, H., Iwasaki, S., Takei, Y. A., Sasaki, M., Usui, S., Okazaki, M., Takahashi, S., Ono, M., Nose, M., Sakai, J., Fujino, T., Yamamoto, T. T.
|
|
<strong>Severe hypercholesterolemia, impaired fat tolerance, and advanced atherosclerosis in mice lacking both low density lipoprotein receptor-related protein 5 and apolipoprotein E.</strong>
|
|
J. Biol. Chem. 278: 11331-11336, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12509421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12509421</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12509421" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M211987200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Mao2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mao, J., Wang, J., Liu, B., Pan, W., Farr, G. H., III, Flynn, C., Yuan, H., Takada, S., Kimelman, D., Li, L., Wu, D.
|
|
<strong>Low-density lipoprotein receptor-related protein-5 binds to axin and regulates the canonical Wnt signaling pathway.</strong>
|
|
Molec. Cell 7: 801-809, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11336703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11336703</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11336703" 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/s1097-2765(01)00224-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Mizuguchi2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mizuguchi, T., Furuta, I., Watanabe, Y., Tsukamoto, K., Tomita, H., Tsujihata, M., Ohta, T., Kishino, T., Matsumoto, N., Minakami, H., Niikawa, N., Yoshiura, K.
|
|
<strong>LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant for bone mineral density.</strong>
|
|
J. Hum. Genet. 49: 80-86, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14727154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14727154</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14727154" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s10038-003-0111-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Narumi2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Narumi, S., Numakura, C., Shiihara, T., Seiwa, C., Nozaki, Y., Yamagata, T., Momoi, M. Y., Watanabe, Y., Yoshino, M., Matsuishi, T., Nishi, E., Kawame, H., Akahane, T., Nishimura, G., Emi, M., Hasegawa, T.
|
|
<strong>Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma syndrome: identification of a 7.2-kb microdeletion using oligonucleotide tiling microarray.</strong>
|
|
Am. J. Med. Genet. 152A: 133-140, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20034086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20034086</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20034086" 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/ajmg.a.33177" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Price1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Price, S. M., Periam, N., Humphries, A., Woodruff, G., Trembath, R. C.
|
|
<strong>Familial exudative vitreoretinopathy linked to D11S533 in a large Asian family with consanguinity.</strong>
|
|
Ophthalmic Genet. 17: 53-57, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8832721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8832721</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8832721" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.3109/13816819609057871" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Qin2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Qin, M., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K., Kondo, H.
|
|
<strong>Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes.</strong>
|
|
Hum. Mutat. 26: 104-112, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15981244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15981244</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15981244" 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/humu.20191" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Qin2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Qin, M., Kondo, H., Tahira, T., Hayashi, K.
|
|
<strong>Moderate reduction of Norrin signaling activity associated with the causative missense mutations identified in patients with familial exudative vitreoretinopathy.</strong>
|
|
Hum. Genet. 122: 615-623, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17955262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17955262</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17955262" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s00439-007-0438-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Renton2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Renton,T., Odell, E., Drage, N. A.
|
|
<strong>Differential diagnosis and treatment of autosomal dominant osteosclerosis of the mandible.</strong>
|
|
Brit. J. Oral Maxillofac. Surg. 40: 55-59, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11883972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11883972</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11883972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1054/bjom.2001.0719" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Scopelliti1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Scopelliti, D., Orsini, R., Ventucci, D., Carratelli, D.
|
|
<strong>Malattia di Van Buchem.</strong>
|
|
Minerva Stomatol. 48: 227-234, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10434540/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10434540</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10434540" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Semenov2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Semenov, M., Tamai, K., He, X.
|
|
<strong>SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor.</strong>
|
|
J. Biol. Chem. 280: 26770-26775, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15908424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15908424</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15908424" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M504308200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Shastry1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shastry, B. S., Trese, M. T.
|
|
<strong>Familial exudative vitreoretinopathy: further evidence for genetic heterogeneity. (Letter)</strong>
|
|
Am. J. Med. Genet. 69: 217-218, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9056564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9056564</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9056564" 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/(sici)1096-8628(19970317)69:2<217::aid-ajmg19>3.0.co;2-o" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Toomes2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Toomes, C., Bottomley, H. M., Jackson, R. M., Towns, K. V., Scott, S., Mackey, D. A., Craig, J. E., Jiang, L., Yang, Z., Trembath, R., Woodruff, G., Gregory-Evans, C. Y., Gregory-Evans, K., Parker, M. J., Black, G. C. M., Downey, L. M., Zhang, K., Inglehearn, C. F.
|
|
<strong>Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q.</strong>
|
|
Am. J. Hum. Genet. 74: 721-730, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15024691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15024691</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15024691[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15024691" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/383202" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Twells2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Twells, R. C. J., Mein, C. A., Phillips, M. S., Hess, J. F., Veijola, R., Gilbey, M., Bright, M., Metzker, M., Lie, B. A., Kingsnorth, A., Gregory, E., Nakagawa, Y., and 12 others.
|
|
<strong>Haplotype structure, LD blocks, and uneven recombination within the LRP5 gene.</strong>
|
|
Genome Res. 13: 845-855, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12727905/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12727905</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12727905[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12727905" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1101/gr.563703" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Twells2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Twells, R. C. J., Metzker, M. L., Brown, S. D., Cox, R., Garey, C., Hammond, H., Hey, P. J., Levy, E., Nakagawa, Y., Philips, M. S., Todd, J. A., Hess, J. F.
|
|
<strong>The sequence and gene characterization of a 400-kb candidate region for IDDM4 on chromosome 11q13.</strong>
|
|
Genomics 72: 231-242, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11401438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11401438</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11401438" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.2000.6492" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Van Hul2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Van Hul, E., Gram, J., Bollerslev, J., Van Wesenbeeck, L., Mathysen, E., Andersen, P. E., Vanhoenacker, F., Van Hul, W.
|
|
<strong>Localization of the gene causing autosomal dominant osteopetrosis type I to chromosome 11q12-13.</strong>
|
|
J. Bone Miner. Res. 17: 1111-1117, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12054167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12054167</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12054167" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1359/jbmr.2002.17.6.1111" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Van Wesenbeeck2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Van Wesenbeeck, L., Cleiren, E., Gram, J., Beals, R. K., Benichou, O., Scopelliti, D., Key, L., Renton, T., Bartels, C., Gong, Y., Warman, M. L., de Vernejoul, M.-C., Bollerslev, J., Van Hul, W.
|
|
<strong>Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density.</strong>
|
|
Am. J. Hum. Genet. 72: 763-771, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12579474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12579474</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12579474[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12579474" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/368277" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Xia2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Xia, W., Hu, J., Liu, F., Ma, J., Sun, S., Zhang, J., Jin, K., Huang, J., Jiang, N., Wang, X., Li, W., Ma, Z., Ma, D.
|
|
<strong>New role of LRP5, associated with nonsyndromic autosomal-recessive hereditary hearing loss.</strong>
|
|
Hum. Mutat. 38: 1421-1431, 2017. Note: Erratum: Hum. Mutat. 39: 882 only, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28677207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28677207</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28677207" 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/humu.23285" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Yadav2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yadav, V. K., Ryu, J.-H., Suda, N., Tanaka, K. F., Gingrich, J. A., Schutz, G., Glorieux, F. H., Chiang, C. Y., Zajac, J. D., Insogna, K. L., Mann, J. J., Hen, R., Ducy, P., Karsenty, G.
|
|
<strong>Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum.</strong>
|
|
Cell 135: 825-837, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19041748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19041748</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19041748[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19041748" 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.cell.2008.09.059" 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">
|
|
Anne M. Stumpf - updated : 03/15/2023
|
|
</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">
|
|
Marla J. F. O'Neill - updated : 03/15/2023<br>Marla J. F. O'Neill - updated : 05/10/2021<br>Cassandra L. Kniffin - updated : 02/19/2018<br>Marla J. F. O'Neill - updated : 3/13/2013<br>Marla J. F. O'Neill - updated : 9/8/2011<br>Patricia A. Hartz - updated : 3/20/2009<br>Marla J. F. O'Neill - updated : 3/12/2008<br>Marla J. F. O'Neill - updated : 1/2/2008<br>Patricia A. Hartz - updated : 3/23/2007<br>Patricia A. Hartz - updated : 3/1/2007<br>Marla J. F. O'Neill - updated : 1/12/2007<br>Cassandra L. Kniffin - updated : 8/14/2006<br>Patricia A. Hartz - updated : 11/9/2005<br>Victor A. McKusick - updated : 10/14/2005<br>Patricia A. Hartz - updated : 9/1/2005<br>Victor A. McKusick - updated : 10/21/2004<br>Victor A. McKusick - updated : 4/27/2004<br>Victor A. McKusick - updated : 4/8/2004<br>Cassandra L. Kniffin - updated : 5/15/2003<br>Victor A. McKusick - updated : 2/28/2003<br>Victor A. McKusick - updated : 1/29/2003<br>Dawn Watkins-Chow - updated : 11/8/2002<br>Victor A. McKusick - updated : 6/7/2002<br>Deborah L. Stone - updated : 1/23/2002<br>Stylianos E. Antonarakis - updated : 11/20/2001<br>Stylianos E. Antonarakis - updated : 8/6/2001<br>Patti M. Sherman - updated : 5/10/1999<br>Sheryl A. Jankowski - updated : 4/12/1999
|
|
</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">
|
|
Sheryl A. Jankowski : 2/9/1999
|
|
</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">
|
|
carol : 09/09/2024
|
|
</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 : 06/08/2023<br>carol : 04/28/2023<br>alopez : 03/24/2023<br>alopez : 03/21/2023<br>alopez : 03/15/2023<br>alopez : 03/15/2023<br>carol : 05/11/2021<br>carol : 05/10/2021<br>carol : 02/23/2018<br>carol : 02/22/2018<br>carol : 02/22/2018<br>carol : 02/21/2018<br>ckniffin : 02/19/2018<br>alopez : 07/15/2015<br>mcolton : 7/13/2015<br>carol : 4/3/2014<br>carol : 3/14/2013<br>terry : 3/13/2013<br>terry : 3/13/2013<br>carol : 9/8/2011<br>terry : 9/8/2011<br>mgross : 3/20/2009<br>terry : 3/20/2009<br>wwang : 3/17/2008<br>terry : 3/12/2008<br>carol : 1/18/2008<br>carol : 1/2/2008<br>carol : 10/3/2007<br>carol : 7/27/2007<br>mgross : 3/23/2007<br>mgross : 3/1/2007<br>carol : 1/17/2007<br>terry : 1/12/2007<br>wwang : 8/23/2006<br>ckniffin : 8/14/2006<br>terry : 3/22/2006<br>mgross : 12/1/2005<br>terry : 11/9/2005<br>alopez : 10/17/2005<br>terry : 10/14/2005<br>mgross : 9/7/2005<br>terry : 9/1/2005<br>alopez : 10/25/2004<br>terry : 10/21/2004<br>alopez : 4/28/2004<br>terry : 4/27/2004<br>tkritzer : 4/26/2004<br>tkritzer : 4/16/2004<br>terry : 4/8/2004<br>tkritzer : 3/22/2004<br>carol : 12/9/2003<br>cwells : 7/17/2003<br>terry : 7/9/2003<br>cwells : 5/21/2003<br>ckniffin : 5/15/2003<br>alopez : 3/19/2003<br>alopez : 3/19/2003<br>carol : 3/10/2003<br>tkritzer : 3/7/2003<br>tkritzer : 3/6/2003<br>terry : 2/28/2003<br>tkritzer : 1/31/2003<br>terry : 1/29/2003<br>tkritzer : 1/7/2003<br>carol : 11/8/2002<br>carol : 11/8/2002<br>terry : 6/7/2002<br>carol : 1/23/2002<br>carol : 1/23/2002<br>mgross : 11/20/2001<br>mgross : 11/20/2001<br>mgross : 8/6/2001<br>psherman : 5/24/1999<br>psherman : 5/17/1999<br>psherman : 5/10/1999<br>psherman : 4/12/1999<br>psherman : 2/9/1999
|
|
</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> 603506
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 5; LRP5
|
|
|
|
</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">
|
|
LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 7; LRP7<br />
|
|
LR3
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: LRP5</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 1264041000, 254112001, 254131007;
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 11q13.2
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 11:68,298,412-68,449,275 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype 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>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="6">
|
|
<span class="mim-font">
|
|
11q13.2
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
[Bone mineral density variability 1]
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
601884
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Endosteal hyperostosis
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
144750
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Exudative vitreoretinopathy 4
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
601813
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant; Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Osteopetrosis, autosomal dominant 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
607634
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Osteoporosis-pseudoglioma syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
259770
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Polycystic liver disease 4 with or without kidney cysts
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
617875
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The LRP5 gene encodes a transmembrane protein that acts as a coreceptor with Frizzled protein family members (e.g., FZD1, 603408) for transducing signals by Wnt proteins (see 164820) (summary by Cnossen et al., 2014). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Members of the low density lipoprotein receptor (LDLR) family are cell surface proteins that bind and internalize ligands in the process of receptor-mediated endocytosis. To identify candidate genes for the type I diabetes IDDM4 (600319) locus in 11q13, Hey et al. (1998) constructed an approximately 200-kb cosmid and BAC contig of this region. By DNA sequencing and by searching sequence databases, they identified a novel member of the LDLR family, which they named LDLR-related protein-5 (LRP5). The LRP5 cDNA encodes a deduced 1,615-amino acid protein containing conserved modules characteristic of the LDLR family, including a putative signal peptide, 4 epidermal growth factor (EGF) repeats with associated spacer domains, 3 LDLR repeats, a single transmembrane-spanning domain, and a cytoplasmic domain. The extracellular domain of LRP5 contains 6 potential N-linked glycosylation sites. Of the known family members, LRP5 is most closely related to LRP1 (107770). However, LRP5 has a unique organization of EGF and LDLR repeats compared to other LDLR family members and likely represents a new category in this family. Northern blot analysis detected an approximately 5.1- to 5.6-kb LRP5 mRNA in a variety of human tissues, with the highest level of expression in the liver. </p><p>Hey et al. (1998) cloned a mouse Lrp5 cDNA and found that the deduced protein is 94% identical to human LRP5. Using immunohistochemistry in Lrp5 knockout mice, Kato et al. (2002) determined that Lrp5 is expressed in the osteoblasts lining the endosteal and trabecular bone surfaces. </p><p>Independently, Dong et al. (1998) isolated an LRP5 cDNA from a human osteoblast cDNA library. The authors designated the encoded protein LR3 to reflect its 3 ligand-binding domains. Dot blot analysis of a variety of human adult and fetal tissues detected highest LR3 expression in the aorta, and Northern blot analysis detected a 5.4-kb LR3 message in all human tissues examined except the brain. Dong et al. (1998) demonstrated that mouse NIH 3T3 cells transfected with LRP5 show increased cell proliferation. </p><p>In situ studies of rat tibia by Little et al. (2002) showed expression of LRP5 in areas of bone involved in remodeling. Northern blot analysis revealed that LRP5 was transcribed in human bone tissue as well as in numerous other tissues. </p><p>Cnossen et al. (2014) found abundant expression of the LRP5 gene in liver tissue, specifically in the epithelium lining bile ducts. </p><p>Using in situ hybridization probes in zebrafish embryos, Xia et al. (2017) observed widespread expression of lrp5 at 24, 30, and 48 hours postfertilization. The authors noted that expression was clustered around the otic vesicle, suggesting that lrp5 might contribute to hearing development. Using immunohistochemistry to identify expression in the mouse inner ear, they observed Lrp5 expression in cochlear sensory epithelial cells. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By fluorescence in situ hybridization (FISH), Hey et al. (1998) mapped a mouse BAC clone containing the Lrp5 gene to chromosome 19, which shows homology of synteny with human 11q13. Chen et al. (1999) mapped the human LRP5 gene to 11q13.4 by FISH and between markers D11S24270 and D11S1975 by radiation hybrid mapping. They mapped the mouse Lrp5 gene to chromosome 19B by FISH. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By genomic sequence analysis, Gong et al. (2001) determined that the LRP5 gene contains 23 coding exons and spans more than 100 kb. Twells et al. (2001) determined that the LRP5 gene spans 160 kb. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Gong et al. (2001) demonstrated LRP5 expression by osteoblasts in situ and showed that LRP5 can transduce Wnt signaling in vitro via the canonical pathway. They further showed that a mutant secreted form of Lrp5 could reduce bone thickness in mouse calvarial explant cultures. These data indicated that Wnt-mediated signaling via LRP5 affects bone accrual during growth and is important for the establishment of peak bone mass. </p><p>Mao et al. (2001) identified axin (603816) as a protein that interacts with the intracellular domain of LRP5. LRP5, when expressed in fibroblast cells, showed no effect on the canonical Wnt signaling pathway by itself, but acted synergistically with Wnt. In contrast, LRP5 mutants lacking the extracellular domain functioned as constitutively active forms that bound axin and that induced LEF1 (153245) activation by destabilizing axin and stabilizing beta-catenin (116806). Addition of Wnt caused the translocation of axin to the membrane and enhanced the interaction between axin and LRP5. In addition, the LRP5 sequences involved in interactions with axin were found to be required for LEF1 activation. The authors concluded that the binding of axin to LRP5 is an important part of the Wnt signal transduction pathway. LRP5 also acts as a target for the inhibitory effects of Dickkopf (DKK1; 605189), another developmental protein, on Wnt signaling. </p><p>Semenov et al. (2005) found that human SOST (605740) antagonized Wnt signaling in Xenopus embryos and mammalian cells by binding to the extracellular domains of the Wnt coreceptors Lrp5 and Lrp6 (603507) and disrupting Wnt-induced frizzled (see 603408)-Lrp complex formation. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Twells et al. (2003) identified 95 SNPs within a 269-kb region containing LRP5 and its 3 flanking genes in several families of white European origin. They found a high level of recombination across LRP5, including a hotspot region from intron 1 to intron 7, where there were 109 recombinants/Mb (4,882 meioses), in contrast to flanking regions of 14.6 recombinants/Mb. </p><p><strong><em>Osteoporosis-Pseudoglioma Syndrome</em></strong></p><p>
|
|
Gong et al. (2001) showed that LRP5 affects bone mass accrual during growth and identified mutations in the LRP5 gene (e.g., 603506.0001) that cause autosomal recessive osteoporosis-pseudoglioma syndrome (OPPG; 259770). They found that obligate carriers of mutant LRP5 genes had reduced bone mass when compared to age- and gender-matched controls. </p><p>Ai et al. (2005) sequenced the coding exons of LRP5 in 37 probands suspected of having OPPG on the basis of the cooccurrence of severe congenital or childhood-onset visual impairment with bone fragility or osteoporosis recognized by young adulthood. They found 2 putative mutant alleles in 26 probands, only 1 mutant allele in 4 probands, and no mutant alleles in 7 probands. Looking for digenic inheritance, they sequenced the genes encoding the functionally related receptor LRP6 (603507), an LRP5 coreceptor FZD4 (604579), and the LRP5 ligand norrin (NDP; 300658), in the 4 probands with 1 mutant allele, and, looking for locus heterogeneity, they sequenced FZD4 and NDP in the 7 probands with no mutations; no additional mutations were found. They compared clinical features between probands with and those without LRP5 mutations and found no difference in the severity of skeletal disease, prevalence of cognitive impairment, or family history of consanguinity. However, 4 of the 7 probands without detectable mutations had eye pathology that differed from pathology previously described for OPPG. Since many LRP5 mutations are missense changes, to differentiate between a disease-causing mutation and a benign variant Ai et al. (2005) measured the ability of wildtype and mutant LRP5 to transduce Wnt (see 164820) and Norrin signal ex vivo. Each of the 7 OPPG mutations tested had reduced signal transduction compared with wildtype mutations. These results indicated that early bilateral vitreoretinal eye pathology coupled with skeletal fragility is a strong predictor of LRP5 mutation and that mutations in LRP5 cause OPPG by impairing WNT and Norrin signal transduction. </p><p><strong><em>Familial Exudative Vitreoretinopathy 4</em></strong></p><p>
|
|
Familial exudative vitreoretinopathy (see EVR1; 133780) is an inherited disorder of retinal vessel development (Benson, 1995). EVR1 is caused by mutation in the FZD4 gene (604579) on chromosome 11q14.2 and has been demonstrated in many of the linked families. The LRP5 gene on chromosome 11q13.4 came under suspicion as a candidate gene for FEVR because of involvement of the eyes in some disorders, notably OPPG, which are caused by LRP5 mutation. In affected members of 6 different families with autosomal dominant EVR4 (601813), Toomes et al. (2004) identified 6 different heterozygous mutations in the LRP5 gene (see, e.g., 603506.0020-603506.0021). </p><p>Jiao et al. (2004) studied 3 consanguineous families of European descent in which autosomal recessive FEVR was diagnosed in multiple individuals. Sequencing of LRP5 showed, in all 3 families, homozygosity for mutation in LRP5: R570Q (603506.0022), R752G (603506.0023), and E1367K (603506.0024). Thus, mutations in the LRP5 gene can cause autosomal recessive as well as autosomal dominant FEVR. </p><p>Qin et al. (2005) identified 9 novel mutations in the LRP5 gene (see, e.g., 603506.0025-603506.0028) in Japanese patients with FEVR. Four families showed autosomal dominant inheritance, and 2 families showed autosomal recessive inheritance. One family was found to have a heterozygous mutation in the LRP5 gene (603506.0026) and a heterozygous mutation in the FZD4 gene (604579.0003) on the same chromosome. Qin et al. (2005) also found that patients with mutations in the LRP5 gene showed reduced bone mineral density and suggested that it is a common feature in patients with EVR4. Qin et al. (2005) proposed that OPPG and EVR4 are part of a single phenotypic spectrum with both ocular and bone manifestations. </p><p>Using standard PCR-based sequencing, Narumi et al. (2010) analyzed the LRP5 gene in 4 male Japanese patients with typical skeletal and ocular features of OPPG and identified compound heterozygosity for 1 nonsense and 4 missense mutations in 3 of the patients (603506.0025 and 603506.0029-603506.0032). In the fourth patient, they identified only heterozygosity for a splice site mutation (603506.0033) by sequencing; however, using custom-designed oligonucleotide tiling array CGH targeted to a 600-kb genomic region harboring LRP5, Narumi et al. (2010) identified a 7.2-kb microdeletion within the LRP5 gene (603506.0034) on the patient's second allele. </p><p><strong><em>Association with Bone Density Variation</em></strong></p><p>
|
|
Little et al. (2002) identified a gly171-to-val mutation in the LRP5 gene (G171V; 603506.0013) that results in an autosomal dominant high bone mass trait (see 601884). Boyden et al. (2002) found the same LRP5 mutation in a family with autosomal dominant high bone density associated with square jaw and torus palatinus. </p><p>Van Wesenbeeck et al. (2003) performed mutation analysis of the LRP5 gene in 10 families or isolated patients with various conditions with an increased bone density, including endosteal hyperostosis (144750), van Buchem disease (see 144750), and osteopetrosis type I. Direct sequencing of the LRP5 gene revealed 19 sequence variants, 13 of which were confirmed as polymorphisms, with the remaining 6 novel missense mutations considered likely disease causing (see 603506.0014-603506.0018). Like the G171V mutation (G171V; 603506.0013), which causes the high bone mass phenotype, all mutations were located in the amino-terminal part of the gene, before the first epidermal growth factor-like domain. These results indicated that, despite the different diagnoses that could be made, conditions with an increased bone density affecting mainly the cortices of the long bones and the skull are often caused by mutations in the LRP5 gene. </p><p>Ferrari et al. (2004) tested the hypothesis that polymorphisms in the LRP5 gene contribute to bone mass determination in the general population. In a cross-sectional study of 889 healthy whites of both sexes, they found significant association for a missense substitution in exon 9 with lumbar spine bone mineral content, with bone area, and with stature. The associations were observed mainly in adult men, in whom LRP5 polymorphisms accounted for less than 15% of the variance of the traits. Haplotype analysis suggested that additional genetic variation within the region may contribute to bone mass and size determination. In a study of 1-year gain in vertebral bone mass and size in prepubertal children, they found a significant association in males but not females. </p><p>Mizuguchi et al. (2004) performed an association study between bone mineral density (BMD) and 9 candidate genes in 481 healthy Japanese women. They found that only LRP5 showed a significant association with BMD. A follow-up case-control study of 126 women with osteoporosis (see 166710) and 131 normal controls revealed a significant difference in allelic frequency of the LRP5 2220C-T SNP (603506.0019) (p = 0.009). The authors suggested that LRP5 is a BMD determinant and contributes to a risk of osteoporosis. </p><p><strong><em>Association with Obesity</em></strong></p><p>
|
|
Guo et al. (2006) genotyped 1,873 Caucasian individuals from 405 nuclear families for SNPs and haplotypes of the LRP5 gene and found that the common allele A for SNP4 (rs4988300) and the minor allele G for SNP6 (rs634008) were significantly associated with obesity and body mass index (BMI). Significant associations were also observed between the common haplotype A-G-G-G in block 2 (intron 1) with obesity, BMI, and fat mass (p less than 0.001, p less than 0.001, and p = 0.003, respectively). Guo et al. (2006) concluded that intronic variants of the LRP5 gene are markedly associated with obesity. </p><p><strong><em>Polycystic Liver Disease 4 with or without Kidney Cysts</em></strong></p><p>
|
|
In affected individuals from 4 unrelated families with polycystic liver disease-4 with or without kidney cysts (PCLD4; 617875), Cnossen et al. (2014) identified 4 different heterozygous missense mutations in the in the LRP5 gene (603506.0035-603506.0038). Two mutations affected the extracellular domain, and 2 affected the intracellular domain. The mutation in the first family was found by whole-exome sequencing and confirmed by Sanger sequencing; the 3 other mutations were found by direct sequencing of the LRP5 gene in a cohort of 150 probands with cystic liver disease. The mutations segregated with the disorder in the families, with some evidence for age-dependent incomplete penetrance. In vitro functional expression studies of 2 of the variants showed that they resulted in decreased WNT (see, e.g., 164820) signaling activation in response to Wnt3a (606359) compared to wildtype, as well as altered expression of some target genes in this pathway. None of the patients carrying mutations had evidence of clinical features of other LRP5-related disorders, including bone density or ocular abnormalities. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
|
---Deafness, Autosomal Recessive</p><p>In a Chinese family (WZ-01) in which a brother and sister had nonsyndromic postlingual hearing loss (see 220290) and were negative for mutation in common deafness-associated genes, Xia et al. (2017) performed whole-exome sequencing and identified homozygosity for a G610W missense mutation in the LRP5 gene that was confirmed by Sanger sequencing. The report indicated that the unaffected parents of the affected sibs were the only other family members analyzed by whole-exome sequencing. The authors stated that the mutation was not found in unaffected family members or in 500 ethnically matched controls. Onset of symptoms occurred in the second decade of life, with tinnitus and hearing impairment involving primarily the low and middle frequencies, resulting in a 'valley-shaped' audiogram. CT and MRI imaging of the inner ear was normal. The G610W mutant showed weaker ability than wildtype LRP5 to rescue the lrp5-knockdown phenotype of morphant zebrafish embryos (see ANIMAL MODEL). The authors concluded that LRP5 is a candidate gene for deafness. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Using a norrin-based reporter assay to analyze the effects of FEVR-causing mutations, Qin et al. (2008) demonstrated that a nonsense mutation in FZD4 completely abolished signaling activity, whereas missense mutations in FZD4 and LRP5 caused a moderate level of reduction, and a double missense mutation in both genes caused a severe reduction in activity, correlating roughly with clinical phenotypes. Norrin mutants, however, showed variable effects on signal transduction, and no correlation with clinical phenotypes was observed; norrin mutants also showed impaired cell surface binding. Qin et al. (2008) concluded that norrin signaling is involved in FEVR pathogenesis, but suggested the presence of an unknown parallel pathway at the level of receptor/ligand binding as evidenced by the moderate and variable signal reduction lacking a clear genotype/phenotype correlation. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Kato et al. (2002) generated mice with a targeted disruption of Lrp5 and showed that they develop a low bone mass phenotype. In vivo and in vitro analyses indicated that the phenotype becomes evident postnatally, and demonstrated that it is secondary to decreased osteoblast proliferation and function in a Cbfa1 (600211)-independent manner. The mice also displayed persistent embryonic eye vascularization due to a failure of macrophage-induced endothelial cell apoptosis. DNA cotransfection and coimmunoprecipitation experiments showed that Lrp5 binds directly to Wnt proteins. RT-PCR experiments showed that expression of proteins in the Wnt signaling pathway was affected by Lrp5 disruption. The phenotype of the Lrp5-deficient mice phenotype mirrored human osteoporosis-pseudoglioma syndrome. </p><p>Clement-Lacroix et al. (2005) found that lithium restored bone metabolism and bone mass to near wildtype levels in Lrp5 -/- mice. Lithium activated canonical Wnt signaling in cultured calvarial osteoblasts from Lrp5 -/- mice, and lithium-treated mice had increased expression of Wnt-responsive genes in their bone marrow cells in vivo. Clement-Lacroix et al. (2005) concluded that lithium enhances bone anabolism, at least in part, by activating the Wnt signaling pathway downstream of LRP5. </p><p>LRP5 plays an essential role in bone accrual and eye development. Fujino et al. (2003) showed that LRP5 is also required for normal cholesterol and glucose metabolism. Mice lacking Lrp5 showed increased plasma cholesterol levels when fed a high-fat diet, because of the decreased hepatic clearance of chylomicron remnants. In addition, when fed a normal diet, Lrp5-deficient mice showed a markedly impaired glucose tolerance. The experiments suggested that Wnt/LRP5 signaling contributes to the glucose-induced insulin secretion in islets. </p><p>To study lipoprotein metabolism, Magoori et al. (2003) generated mice lacking both apolipoprotein E (apoE; 107741) and Lrp5. On a normal diet, the double knockout mice older than 4 months of age had 60% higher plasma cholesterol levels than the levels observed with apoE deficiency alone. LRP5 deficiency alone had no significant effects on the plasma cholesterol levels. Analysis showed that the very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions were markedly increased in the double knockout mice. Atherosclerotic lesions in the double knockout mice at age 6 months were severe, with destruction of the internal elastic lamina. </p><p>Yadav et al. (2008) identified Tph1 (191060), which encodes the rate-limiting enzyme in serotonin synthesis, as the most highly overexpressed gene in Lrp5 -/- mice. Tph1 expression was also elevated in Lrp5 -/- duodenal cells, its primary site of expression. Decreasing serotonin blood levels normalized bone formation and bone mass in Lrp5 -/- mice, and gut-specific Lrp5 inactivation decreased bone formation in a beta-catenin-independent manner. Moreover, gut-specific activation of Lrp5 or inactivation of Tph1 increased bone mass and prevented ovariectomy-induced bone loss in mice. Yadav et al. (2008) showed that serotonin determined the extent of bone formation by binding its receptor, Htr1b (182131), on osteoblasts and limiting osteoblast proliferation by inhibiting Creb (see 123810)-mediated cyclin D1 (CCND1; 168461) expression. Yadav et al. (2008) concluded that LRP5 inhibits bone formation by inhibiting serotonin production. </p><p>Cui et al. (2011) generated mice with osteocyte-specific expression of inducible Lrp5 mutations that cause high bone mass (G171V, 603506.0013; A214V, 603506.0017) and observed increased bone mass, bone strength, and bone formation rates in the mutant mice compared to wildtype. Similar studies with a truncating Lrp5 mutation resulted in reduced bone mass in the mutant mice compared to wildtype; inactivation of Lrp5 in the intestine, however, had no significant effect on bone mass. In addition, induction of an Lrp5 mutation in cells that form the appendicular skeleton but not in cells that form the axial skeleton resulted in alterations in bone properties of the limbs but not the spine. Cui et al. (2011) concluded that their findings supported a mechanism in mice in which Lrp5 functions via the canonical Wnt pathway in osteocytes to regulate bone mass rather than regulating bone mass indirectly via other tissues. </p><p>Xia et al. (2017) generated zebrafish morphants with knockdown of lrp5 and observed that the morphants had abnormal numbers of otoliths and smaller otic vesicles than wildtype embryos. In addition, the inner ear structure of morphants was abnormal and disrupted. Morphant neuromasts were smaller and the number of lateral-line neuromasts was lower than in wildtype embryos, and there were fewer hair cells and supporting cells per neuromast. Fewer variable stereocilia were detected in the morphants, and the steriocilia were shorter and thinner than those in wildtype embryos. The morphant phenotype was largely rescued by injection of wildtype LRP5. Morphant zebrafish also showed abnormal swimming behavior, consistent with a defective balance system, and had a reduced C-startle response to sound; LRP5 rescue resulted in about half of the morphants regaining some hearing ability, with increased audio stimulus sensitivity, and swimming postures normalized. Analysis of mRNA expression in morphant and wildtype zebrafish embryos revealed reduced expression in morphants of genes in the Wnt (see 164820) signaling pathway as well as beta-catenin (CTNNB1; 116806), and BrdU analysis showed reduced cell proliferation in morphants compared to wildtype zebrafish. The authors suggested that lrp5 knockdown induced inhibition of cell proliferation through the Wnt/beta-catenin signaling pathway, resulting in hearing loss. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>38 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, TRP10TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908660,
|
|
|
|
|
|
gnomAD: rs121908660,
|
|
|
|
|
|
ClinVar: RCV000006646
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; 259770), Gong et al. (2001) identified a homozygous G-to-A transition at nucleotide 29 of the LRP5 gene, resulting in a trp10-to-ter (W10X) mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, ARG428TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908661,
|
|
|
|
|
|
|
|
ClinVar: RCV000006647, RCV001781193, RCV002496285, RCV003904811
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; 259770), Gong et al. (2001) identified a homozygous C-to-T transition at nucleotide 1282 of the LRP5 gene, resulting in an arg428-to-ter (R428X) mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, 1-BP DEL, 1467G
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1554967141,
|
|
|
|
|
|
|
|
ClinVar: RCV000006648
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; 259770), Gong et al. (2001) identified a homozygous deletion of G at nucleotide 1467 of the LRP5 gene. This mutation produced a frameshift after asp490 (D490). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, ASP718TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908662,
|
|
|
|
|
|
|
|
ClinVar: RCV000006649
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; 259770), Gong et al. (2001) identified a homozygous insertion of T at nucleotide 2150 of the LRP5 gene. This mutation produced a stop codon at asp718 (D718X). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, GLN853TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908663,
|
|
|
|
|
|
|
|
ClinVar: RCV000006650
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; 259770), Gong et al. (2001) identified a homozygous C-to-T transition at nucleotide 2557 of the LRP5 gene, resulting in a gln853-to-ter (Q853X) nonsense mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, 1-BP DEL, 3804A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80358319,
|
|
|
|
|
|
gnomAD: rs80358319,
|
|
|
|
|
|
ClinVar: RCV000006651
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; 259770), Gong et al. (2001) identified a homozygous deletion of A at nucleotide 3804 of the LRP5 gene. This mutation produced a frameshift after glu1270 (E1270). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, ARG494GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908664,
|
|
|
|
|
|
|
|
ClinVar: RCV000006652, RCV000414333, RCV002247255, RCV004742219, RCV005003340
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; 259770), Gong et al. (2001) identified a homozygous G-to-A transition at nucleotide 1481 of the LRP5 gene, resulting in an arg494-to-gln (R494Q) mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, ARG570TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908665,
|
|
|
|
|
|
|
|
ClinVar: RCV000006653, RCV001851703, RCV002276534
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; 259770), Gong et al. (2001) identified a homozygous C-to-T transition at nucleotide 1708 of the LRP5 gene, resulting in an arg570-to-trp (R570W) mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, VAL667MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs4988321,
|
|
|
|
|
|
gnomAD: rs4988321,
|
|
|
|
|
|
ClinVar: RCV000006654, RCV000086953, RCV000250939, RCV002276535, RCV002276536, RCV002496286, RCV004814844
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; 259770), Gong et al. (2001) identified a homozygous G-to-A transition at nucleotide 1999 of the LRP5 gene, resulting in a val667-to-met (V667M) mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, GLU485TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908666,
|
|
|
|
|
|
|
|
ClinVar: RCV000006655
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; 259770), Gong et al. (2001) identified a G-to-T transversion at nucleotide 1453 of the LRP5 gene, resulting in a glu485-to-ter (E485X) mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, TRP734TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908667,
|
|
|
|
|
|
|
|
ClinVar: RCV000006656
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; 259770), Gong et al. (2001) identified a G-to-A transition at nucleotide 2202 of the LRP5 gene, resulting in a trp734-to-ter (W734X) mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, 1-BP DEL, 2305G
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1554971145,
|
|
|
|
|
|
|
|
ClinVar: RCV000006657
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with osteoporosis-pseudoglioma syndrome (OPPG; 259770), Gong et al. (2001) identified a deletion of G at nucleotide 2305 of the LRP5 gene. This mutation produced a frameshift after asp769 (D769). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 HIGH BONE MASS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, GLY171VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908668,
|
|
|
|
|
|
|
|
ClinVar: RCV000006658, RCV002276537, RCV002512843
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with high bone mass (see 601884), Little et al. (2002) identified a heterozygous G-to-T transversion in exon 3 of the LRP5 gene, resulting in a gly171-to-val (G171V) change in a predicted beta-propeller module of the LRP5 protein. This change was not found in the DNA from 275 individuals with normal bone mineral density or from 643 randomly chosen, ethnically diverse individuals. </p><p>Boyden et al. (2002) found the G171V mutation in affected members of a kindred with high bone density, wide and deep mandible, and torus palatinus. Affected members of this family had normal serum calcium and phosphate levels, normal serum levels of parathyroid hormone and vitamin D metabolites, and normal serum levels of acid phosphatase. Serum osteocalcin, a marker of bone formation, was markedly elevated. Affected members of the family had no cranial nerve pulses. They were asymptomatic but noted difficulty staying afloat while swimming. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 OSTEOPETROSIS, AUTOSOMAL DOMINANT 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, GLY171ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908669,
|
|
|
|
|
|
|
|
ClinVar: RCV000006659
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Van Wesenbeeck et al. (2003) found a 511G-C transversion in exon 3 of the LRP5 gene, causing a gly171-to-arg (G171R) mutation, in a previously described Belgian family (kindred F) in which at least 3 members were diagnosed with autosomal dominant osteopetrosis type I (OPTA1; 607634). The father suffered from severe headaches and x-rays showed very dense bones of the skull. His daughter had a very dense cranial base and cortical thickening of the vertebrae and long bones with normal development. His son had dense bones, mainly of the skull. The codon involved in this mutation is the same as that in the gain-of-function gly171-to-val mutation (G171V; 603506.0013) described in 2 other families by Little et al. (2002) and Boyden et al. (2002). The phenotype was different in those 2 families; the family described by Little et al. (2002) had no features other than very dense bones, whereas patients in the other kindred also suffered from a wide, deep mandible and torus palatinus. The clinical and radiologic features of the Belgian family resembled those of the family described by Little et al. (2002), as they did not suffer from an enlarged mandible or torus palatinus. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 ENDOSTEAL HYPEROSTOSIS, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
OSTEOPETROSIS, AUTOSOMAL DOMINANT 1, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, ALA242THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908670,
|
|
|
|
|
|
|
|
ClinVar: RCV000006660, RCV000006661, RCV000383760, RCV004742220
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Van Wesenbeeck et al. (2003) described a 724G-A transition in exon 4 of the LRP5 gene, resulting in an ala242-to-thr (A242T) mutation, in 2 previously described families (kindreds A and B) from Portland, Oregon (Beals, 1976; Beals et al., 2001) in which members were affected with autosomal dominant endosteal hyperostosis (144750). The condition is characterized by cortical thickening of the long bones, with no alteration in external shape, and a remarkable resistance of the bone to fracture. The skeleton was normal in childhood; the affected patients had a normal height, proportion, intelligence, and longevity. Facial metamorphoses occurred in adolescence, as the forehead flattened, the mandible became elongated, and the gonial angle decreased. Torus palatinus developed in the hard palate, which could lead to malocclusion or loss of teeth. The clinical and radiographic features closely resembled those of the kindred described by Boyden et al. (2002), in whom a gly171-to-val mutation (G171V; 603506.0013) was identified. The A242T mutation was also present in a previously described Sardinian family (kindred D; Scopelliti et al., 1999) in which at least 5 members had osteosclerosis of the skull and enlarged mandible. The mutation was also present in a French family in which an affected proband and his brother had autosomal dominant osteopetrosis type I (OPTA1; 607634), osteomyelitis of the jaw, and hearing problems because of small auditory canals. X-rays showed diffuse osteosclerosis of the trabecular and cortical bone and osteosclerosis of the skull with enlargement of the cranial vault. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 ENDOSTEAL HYPEROSTOSIS, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, ALA214THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908671,
|
|
|
|
|
|
|
|
ClinVar: RCV000006663, RCV000786921, RCV005229766
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family from Portland, Oregon (kindred C) with autosomal dominant endosteal hyperostosis (144750), originally described by Beals et al. (2001), Van Wesenbeeck et al. (2003) found a 640G-A transition in exon 3 of the LRP5 gene, resulting in an ala214-to-thr (A214T) mutation. A different mutation involving the same codon (A214V; 603506.0017) was identified in another family (kindred E) diagnosed with a similar phenotype of increased bone density. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 ENDOSTEAL HYPEROSTOSIS, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, ALA214VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908672,
|
|
|
|
|
|
|
|
ClinVar: RCV000006664
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Van Wesenbeeck et al. (2003) identified a 641C-T transition in exon 3 of the LRP5 gene, resulting in an ala214-to-val (A214V) mutation, in a previously described family of English origin (kindred E; Renton et al., 2002) with endosteal hyperostosis (144750), reported as autosomal dominant osteosclerosis manifest by an enlarged mandible (present in the 20-year-old proband and her father), increased gonial angle, and thickened cortical bone. In the father, there were no other clinical signs and the radiographic appearance of the skull was within normal limits. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 OSTEOPETROSIS, AUTOSOMAL DOMINANT 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, THR253ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908673,
|
|
|
|
|
|
|
|
ClinVar: RCV000006665
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Van Wesenbeeck et al. (2003) identified a 758C-T transition in exon 4 of the LRP5 gene, resulting in a thr253-to-ile (T253I) substitution, in 2 previously described and presumably unrelated Danish families (kindreds I and J; Van Hul et al., 2002) diagnosed with autosomal dominant osteopetrosis type I (OPTA1; 607634). In both families, which originated from the same county in Denmark, affected members showed generalized osteosclerosis, most pronounced in the cranial vault, not associated with an increased fracture rate. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 BONE MINERAL DENSITY QUANTITATIVE TRAIT LOCUS 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, 2220C-T
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2306862,
|
|
|
|
|
|
gnomAD: rs2306862,
|
|
|
|
|
|
ClinVar: RCV000006666, RCV000173754, RCV000712233, RCV002277337, RCV002277338
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In adult Japanese women, Mizuguchi et al. (2004) found an association between the T allele of the 2220C-T polymorphism in exon 10 of the LRP5 gene and low bone mineral density (BMND1; 601884). A case-control study of 126 women with osteoporosis (see 166710) and 131 normal controls revealed a significant difference in allelic frequency of the 2220C-T SNP (p = 0.009). The authors suggested that LRP5 is a BMD determinant and contributes to a risk of osteoporosis. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 EXUDATIVE VITREORETINOPATHY 4, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, IVS21DS, T-G, +2
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80358322,
|
|
|
|
|
|
gnomAD: rs80358322,
|
|
|
|
|
|
ClinVar: RCV000006667, RCV000489366, RCV000505032, RCV001267021, RCV004795379, RCV004814845, RCV004821259
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with autosomal dominant exudative vitreoretinopathy (EVR4; 601813) reported by Price et al. (1996), Toomes et al. (2004) identified a heterozygous substitution of the second nucleotide of intron 21 of the LRP5 gene, changing the GT splice donor site to GG (4488+2T-G). The mutation was predicted to lead to deletion of exon 21, resulting in a frameshift at codon 1449 with a premature stop codon following 52 incorrect amino acids. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 EXUDATIVE VITREORETINOPATHY 4, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, 1-BP INS, 4119C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80358321,
|
|
|
|
|
|
|
|
ClinVar: RCV000006668, RCV005089194
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of an American family with autosomal dominant exudative vitreoretinopathy (EVR4; 601813), Toomes et al. (2004) identified a heterozygous 1-bp insertion in exon 20 of the LRP5 gene, 4119insC, resulting in a frameshift at codon 1374 with a premature stop codon following 175 incorrect amino acids. Two asymptomatic members carried the mutation but had not been examined by fluorescein angiography to exclude a very mild phenotype. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 EXUDATIVE VITREORETINOPATHY 4, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, ARG570GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80358312,
|
|
|
|
|
|
|
|
ClinVar: RCV000006669, RCV000623689, RCV003555944, RCV004814846
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family reported by de Crecchio et al. (1998), Jiao et al. (2004) found that sisters with exudative vitreoretinopathy (EVR4; 601813) carried a homozygous 1757G-A transition in 8 of the LRP5 gene, resulting in an arg570-to-gln (R570Q) amino acid substitution. The sisters were diagnosed at ages 5 years and 7 years and had shown typical signs of FEVR. They required multiple procedures including photocoagulation, cryopexy, and vitrectomy. They showed no signs of systemic disease, including fractures, at ages 29 years and 31 years. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 EXUDATIVE VITREORETINOPATHY 4, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, ARG752GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908674,
|
|
|
|
|
|
|
|
ClinVar: RCV000006670, RCV002512844
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with autosomal recessive exudative vitreoretinopathy (EVR4; 601813) reported by Shastry and Trese (1997), Jiao et al. (2004) identified a homozygous 2302C-G transversion in exon 10 of the LRP5 gene, resulting in an arg752-to-gly (R752G) amino acid change in the third YWTD domain of the protein. Two affected sisters also had an affected paternal uncle; these 3 affected individuals were the offspring of consanguineous marriages. Both sisters were diagnosed at 3 years of age, at which time they manifested typical signs of FEVR, including large retinal folds, peripheral traction and exudates, and an avascular demarcation line near the equator and vitreous detachments. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0024 EXUDATIVE VITREORETINOPATHY 4, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, GLU1367LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28939709,
|
|
|
|
|
|
gnomAD: rs28939709,
|
|
|
|
|
|
ClinVar: RCV000006671, RCV004814847
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a brother and sister with familial exudative retinopathy (EVR4; 601813) reported by de Crecchio et al. (1998), Jiao et al. (2004) found a homozygous 414G-A transition in exon 19 of the LRP5 gene, resulting in a glu1367-to-lys (E1367K) amino acid change. The brother and sister were diagnosed with retinal detachments at ages 6 years and 8 years, respectively, and also showed other typical signs of FEVR. They showed no systemic symptoms, such as fractures or traumatic injuries, by ages 12 years and 10 years, respectively. No additional family members were known to be affected. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0025 EXUDATIVE VITREORETINOPATHY 4, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, LEU145PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80358305,
|
|
|
|
|
|
|
|
ClinVar: RCV000006672, RCV000033256
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 Japanese sibs with exudative vitreoretinopathy-4 (EVR4; 601813), Qin et al. (2005) identified a heterozygous 433C-T transition in exon 2 of the LRP5 gene, resulting in a leu145-to-phe (L145F) substitution in a conserved residue in the beta-propeller structure of the protein. The mother, who also carried the mutation, had mild retinal avascularization and significantly decreased bone mineral density (z score of -2.5). </p><p>In a 23-year-old Japanese man with pseudoglioma and multiple fractures due to osteopenia (OPPG; 259770), Narumi et al. (2010) identified compound heterozygosity for the L145F mutation and a 1655T-C transition in the LRP5 gene, resulting in a thr552-to-met (T552M; 603506.0029) substitution at a highly conserved residue in the second YWTD-EGF-like domain. The patient, who had normal intelligence, had microphthalmia and retinal detachment in the left eye and persistent hyperplasia of the primary vitreous in the right eye. Radiography revealed osteopenia, kyphoscoliosis, and platyspondyly in all vertebrae; he became wheelchair-dependent at 11 years of age due to multiple compression fractures. His unaffected mother was heterozygous for L145F; DNA was unavailable from his father. Neither mutation was found in 100 controls. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0026 EXUDATIVE VITREORETINOPATHY 4, DIGENIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, ARG444CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80358308,
|
|
|
|
|
|
gnomAD: rs80358308,
|
|
|
|
|
|
ClinVar: RCV000006673, RCV001376975, RCV004742221
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a Japanese family with exudative vitreoretinopathy-4 (EVR4; 601813), Qin et al. (2005) identified a heterozygous 1330C-T transition in exon 6 of the LRP5 gene, resulting in an arg444-to-cys (R444C) substitution in a conserved residue in the beta-propeller structure of the protein. Affected members of this family also had a heterozygous mutation in the FZD4 gene (R417Q; 604579.0003; Kondo et al., 2003). The 2 mutations cosegregated in the family, indicating that both mutations were located on the same chromosomes consistent with digenic inheritance. The ocular phenotype in this family tended to be more severe compared to that seen in a family with the FZD4 R417Q mutation alone (Kondo et al., 2003). In addition, the proband in the family with both mutations had reduced bone mass (z score of -2.1), whereas the proband carrying the FZD4 mutation alone had a normal bone mineral density. Qin et al. (2005) concluded that the 2 mutations showed a synergistic deleterious effect in this family. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0027 EXUDATIVE VITREORETINOPATHY 4, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, GLY610ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80358313,
|
|
|
|
|
|
gnomAD: rs80358313,
|
|
|
|
|
|
ClinVar: RCV000006674, RCV001579335, RCV004814848
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese girl with exudative vitreoretinopathy-4 (EVR4; 601813), Qin et al. (2005) identified compound heterozygosity for 2 mutations in the LRP5 gene: a 1828G-A transition in exon 9, resulting in a gly610-to-arg (G610R) substitution, and a 10-bp deletion (del803-812; 603506.0028) in exon 4. Each parent was heterozygous for 1 of the mutations. Although neither parent had the ocular phenotype, both showed decreased bone mineral densities. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0028 EXUDATIVE VITREORETINOPATHY 4, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, 10-BP DEL, NT803
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80358307,
|
|
|
|
|
|
|
|
ClinVar: RCV000006675
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 10-bp deletion in the LRP5 gene (del803-812) that was found in compound heterozygous state in a patient with exudative vitreoretinopathy-4 (EVR4; 601813) by Qin et al. (2005), see 603506.0027. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0029 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, THR552MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397514663,
|
|
|
|
|
|
|
|
ClinVar: RCV000033257, RCV003556102
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the thr552-to-met (T552M) mutation in the LRP5 gene that was found in compound heterozygous state in a patient with pseudoglioma and multiple fractures due to osteopenia (OPPG; 259770) by Narumi et al. (2010), see 603506.0025. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0030 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, PRO382LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397514664,
|
|
|
|
|
|
gnomAD: rs397514664,
|
|
|
|
|
|
ClinVar: RCV000033258, RCV001380061
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 18-year-old Japanese male and a 10-year-old Japanese boy with osteoporosis-pseudoglioma syndrome (OPPG; 259770), Narumi et al. (2010) identified compound heterozygosity for a 1145C-T transition in the LRP5 gene, resulting in a pro382-to-leu (P382L) substitution at a highly conserved residue in the second YWTD-EGF-like domain, and another LRP5 mutation. The 18-year-old also carried a 731C-T transition, resulting in a thr244-to-met (T244M; 603506.0031) substitution at a highly conserved residue in the first YWTD-EGF-like domain; the 10-year-old carried a 4600C-T transition, resulting in an arg1534-to-ter (R1534X; 603506.0032) substitution in the cytoplasmic domain. In both families, the unaffected parents were each heterozygous for 1 of the mutations, none of which was found in 100 controls. In addition to their eye and bone findings, both patients had moderate mental retardation. Narumi et al. (2010) noted that the T244M and R1534X mutations had previously been reported in OPPG patients by Ai et al. (2005) and Gong et al. (2001), respectively. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0031 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, THR244MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397514665,
|
|
|
|
|
|
gnomAD: rs397514665,
|
|
|
|
|
|
ClinVar: RCV000033259
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the thr244-to-met (T244M) mutation in the LRP5 gene that was found in compound heterozygous state in a patient with osteoporosis-pseudoglioma syndrome (OPPG; 259770) by Narumi et al. (2010), see 603506.0030. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0032 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, ARG1534TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs149645175,
|
|
|
|
|
|
gnomAD: rs149645175,
|
|
|
|
|
|
ClinVar: RCV000033260
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg1534-to-ter (R1534X) mutation in the LRP5 gene that was found in compound heterozygous state in a patient with osteoporosis-pseudoglioma syndrome (OPPG; 259770) by Narumi et al. (2010), see 603506.0030. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0033 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, IVS7, G-A, +1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1554967176,
|
|
|
|
|
|
|
|
ClinVar: RCV000033261
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-year-old Japanese boy with osteoporosis-pseudoglioma syndrome (OPPG; 259770), Narumi et al. (2010) identified compound heterozygosity for a splice site transition (1584+1G-A) in intron 7 and a 7.2-kb microdeletion encompassing exons 22 and 23 (603506.0034) of the LRP5 gene. The unaffected parents were each heterozygous for 1 of the mutations, neither of which was found in 100 controls. Sequencing of a mutant RT-PCR fragment indicated that the splice site mutation caused cryptic splice donor site utilization 63-bp downstream of the native exon/intron junction, predicted to add an extra 21 amino acids without a termination codon after glu528 (E528_V529ins21). The 7.2-kb microdeletion was discovered using custom-designed oligonucleotide tiling array CGH targeted to a 600-kb genomic region harboring LRP5; Narumi et al. (2010) stated that this was one of the smallest deletions identified by aCGH-based analyses. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0034 OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, 7.2-KB DEL, EXONS 22-23
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000033262
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 7.2-kb microdeletion encompassing exons 22 and 23 of the LRP5 gene that was found in compound heterozygous state in a patient with osteoporosis-pseudoglioma syndrome (OPPG; 259770) by Narumi et al. (2010), see 603506.0033. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0035 POLYCYSTIC LIVER DISEASE 4 WITH OR WITHOUT KIDNEY CYSTS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, ARG1188TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs141178995,
|
|
|
|
|
|
gnomAD: rs141178995,
|
|
|
|
|
|
ClinVar: RCV000149786, RCV000584769, RCV002516009, RCV005003492
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 19 affected individuals from a large multigenerational Dutch family with polycystic liver disease-4 with or without kidney cysts (PCLD4; 617875), Cnossen et al. (2014) identified a heterozygous c.3562C-T transition in the LRP5 gene, resulting in an arg1188-to-trp (R1188W) substitution at a highly conserved residue in the extracellular domain that was predicted to disrupt a beta-propeller domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the 1000 Genomes Project or Exome Sequencing Project databases or in 2,300 in-house controls. The findings were also confirmed by linkage analysis. There were a few younger unaffected carriers, suggesting age-related incomplete penetrance. Liver tissue from the proband showed intense LRP5 immunostaining of cyst-lining epithelium and bile ducts. In vitro functional expression studies showed that the variant resulted in decreased WNT (see, e.g., 164820) signaling activation in response to Wnt3a (606359) compared to wildtype, as well as altered expression of some target genes in this pathway. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0036 POLYCYSTIC LIVER DISEASE 4 WITH OR WITHOUT KIDNEY CYSTS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, VAL454MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs373910016,
|
|
|
|
|
|
gnomAD: rs373910016,
|
|
|
|
|
|
ClinVar: RCV000162092, RCV000584798, RCV002277318, RCV002515121, RCV004815255, RCV005049440
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 86-year-old Dutch woman and her 49-year-old daughter with polycystic liver disease-4 with or without kidney cysts (PCLD4; 617875), Cnossen et al. (2014) identified a heterozygous c.1360G-A transition in the LRP5 gene, resulting in a val454-to-met (V454M) substitution at a highly conserved residue in the extracellular domain. The mutation was found by direct sequencing of the LRP5 gene in a cohort of 150 probands with cystic liver disease; it was not found in online exome sequencing databases, in in-house samples, or in 1,000 Dutch controls. Functional studies of the variant and studies of patient cells were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0037 POLYCYSTIC LIVER DISEASE 4 WITHOUT KIDNEY CYSTS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, ARG1529SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs724159826,
|
|
|
|
|
|
gnomAD: rs724159826,
|
|
|
|
|
|
ClinVar: RCV000149787, RCV000584817
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Moroccan woman and her 2 adult daughters with polycystic liver disease-4 without kidney cysts (PCLD4; 617875), Cnossen et al. (2014) identified a heterozygous c.4587G-C transversion in the LRP5 gene, resulting in an arg1529-to-ser (R1529S) substitution at a highly conserved residue in the intracellular domain. The mutation was found by direct sequencing of the LRP5 gene in a cohort of 150 probands with cystic liver disease; it was not found in online exome sequencing databases, in in-house samples, or in 525 Moroccan controls. Functional studies of the variant and studies of patient cells were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0038 POLYCYSTIC LIVER DISEASE 4 WITH KIDNEY CYSTS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LRP5, ASP1551ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs724159827,
|
|
|
|
|
|
gnomAD: rs724159827,
|
|
|
|
|
|
ClinVar: RCV000149788, RCV000584765, RCV005008056, RCV005089721
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 65-year-old Dutch man with polycystic liver disease-4 with kidney cysts (PCLD4; 617875), Cnossen et al. (2014) identified a heterozygous c.4651G-A transition in the LRP5 gene, resulting in an asp1551-to-asn (D1551N) substitution at a highly conserved residue in the intracellular domain. The mutation was found by direct sequencing of the LRP5 gene in a cohort of 150 probands with cystic liver disease; it was not found in online exome sequencing databases, in in-house samples, or in 1,000 Dutch controls. The patient had no family history of the disorder. In vitro functional expression studies showed that the variant resulted in decreased WNT (see, e.g., 164820) signaling activation in response to Wnt3a (606359) compared to wildtype, as well as altered expression of some target genes in this pathway. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ai, M., Heeger, S., Bartels, C. F., Schelling, D. K., Osteoporosis-Pseudoglioma Collaborative Group.
|
|
<strong>Clinical and molecular findings in osteoporosis-pseudoglioma syndrome.</strong>
|
|
Am. J. Hum. Genet. 77: 741-753, 2005.
|
|
|
|
|
|
[PubMed: 16252235]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/497706]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Beals, R. K., McLoughlin, S. W., Teed, R. L., McDonald, C.
|
|
<strong>Dominant endosteal hyperostosis: skeletal characteristics and review of the literature.</strong>
|
|
J. Bone Joint Surg. Am. 83: 1643-1649, 2001.
|
|
|
|
|
|
[PubMed: 11701785]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Beals, R. K.
|
|
<strong>Endosteal hyperostosis.</strong>
|
|
J. Bone Joint Surg. Am. 58: 1172-1173, 1976.
|
|
|
|
|
|
[PubMed: 1002767]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Benson, W. E.
|
|
<strong>Familial exudative vitreoretinopathy.</strong>
|
|
Trans. Am. Ophthal. Soc. 93: 473-521, 1995.
|
|
|
|
|
|
[PubMed: 8719692]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Boyden, L. M., Mao, J., Belsky, J., Mitzner, L., Farhi, A., Mitnick, M. A., Wu, D., Insogna, K., Lifton, R. P.
|
|
<strong>High bone density due to a mutation in LDL-receptor-related protein 5.</strong>
|
|
New Eng. J. Med. 346: 1513-1521, 2002.
|
|
|
|
|
|
[PubMed: 12015390]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa013444]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, D., Lathrop, W., Dong, Y.
|
|
<strong>Molecular cloning of mouse Lrp7(Lr3) cDNA and chromosomal mapping of orthologous genes in mouse and human.</strong>
|
|
Genomics 55: 314-321, 1999.
|
|
|
|
|
|
[PubMed: 10049586]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1998.5688]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Clement-Lacroix, P., Ai, M., Morvan, F., Roman-Roman, S., Vayssiere, B., Belleville, C., Estrera, K., Warman, M. L., Baron, R., Rawadi, G.
|
|
<strong>Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 17406-17411, 2005.
|
|
|
|
|
|
[PubMed: 16293698]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0505259102]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cnossen, W. R., te Morsche, R. H. M., Hoischen, A., Gilissen, C., Chrispijn, M., Venselaar, H., Mehdi, S., Bergmann, C., Veltman, J. A., Drenth, J. P. H.
|
|
<strong>Whole-exome sequencing reveals LRP5 mutations and canonical Wnt signaling associated with hepatic cystogenesis.</strong>
|
|
Proc. Nat. Acad. Sci. 111: 5343-5348, 2014.
|
|
|
|
|
|
[PubMed: 24706814]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.1309438111]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cui, Y., Niziolek, P. J., MacDonald, B. T., Zylstra, C. R., Alenina, N., Robinson, D. R., Zhong, Z., Matthes, S., Jacobsen, C. M., Conlon, R. A., Brommage, R., Liu, Q., and 11 others.
|
|
<strong>Lrp5 functions in bone to regulate bone mass.</strong>
|
|
Nature Med. 17: 684-691, 2011.
|
|
|
|
|
|
[PubMed: 21602802]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nm.2388]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
de Crecchio, G., Simonelli, F., Nunziata, G., Mazzeo, S., Greco, G. M., Rinaldi, E., Ventruto, V., Ciccodicola, A., Miano, M. G., Testa, F., Curci, A., D'Urso, M. M., Rinaldi, M. M., Cavaliere, M. L., Castelluccio, P.
|
|
<strong>Autosomal recessive familial exudative vitreoretinopathy: evidence for genetic heterogeneity.</strong>
|
|
Clin. Genet. 54: 315-320, 1998.
|
|
|
|
|
|
[PubMed: 9831343]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.1998.5440409.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dong, Y., Lathrop, W., Weaver, D., Qiu, Q., Cini, J., Bertolini, D., Chen, D.
|
|
<strong>Molecular cloning and characterization of LR3, a novel LDL receptor family protein with mitogenic activity.</strong>
|
|
Biochem. Biophys. Res. Commun. 251: 784-790, 1998.
|
|
|
|
|
|
[PubMed: 9790987]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.1998.9545]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ferrari, S. L., Deutsch, S., Choudhury, U., Chevalley, T., Bonjour, J.-P., Dermitzakis, E. T., Rizzoli, R., Antonarakis, S. E.
|
|
<strong>Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with variation in vertebral bone mass, vertebral bone size, and stature in whites.</strong>
|
|
Am. J. Hum. Genet. 74: 866-875, 2004.
|
|
|
|
|
|
[PubMed: 15077203]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/420771]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fujino, T., Asaba, H., Kang, M.-J., Ikeda, Y., Sone, H., Takada, S., Kim, D.-H., Ioka, R. X., Ono, M., Tomoyori, H., Okubo, M., Murase, T., and 13 others.
|
|
<strong>Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion.</strong>
|
|
Proc. Nat. Acad. Sci. 100: 229-234, 2003.
|
|
|
|
|
|
[PubMed: 12509515]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0133792100]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., Zacharin, M., Oexle, K., and 50 others.
|
|
<strong>LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.</strong>
|
|
Cell 107: 513-523, 2001.
|
|
|
|
|
|
[PubMed: 11719191]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(01)00571-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Guo, Y., Xiong, D., Shen, H., Zhao, L., Xiao, P., Guo, Y., Wang, W., Yang, T., Recker, R. R., Deng, H.
|
|
<strong>Polymorphisms of the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with obesity phenotypes in a large family-based association study.</strong>
|
|
J. Med. Genet. 43: 798-803, 2006.
|
|
|
|
|
|
[PubMed: 16723389]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2006.041715]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hey, P. J., Twells, R. C. J., Phillips, M. S., Nakagawa, Y., Brown, S. D., Kawaguchi, Y., Cox, R., Xie, G., Dugan, V., Hammond, H., Metzker, M. L., Todd, J. A., Hess, J. F.
|
|
<strong>Cloning of a novel member of the low-density lipoprotein receptor family.</strong>
|
|
Gene 216: 103-111, 1998.
|
|
|
|
|
|
[PubMed: 9714764]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0378-1119(98)00311-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jiao, X., Ventruto, V., Trese, M. T., Shastry, B. S., Hejtmancik, J. F.
|
|
<strong>Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5.</strong>
|
|
Am. J. Hum. Genet. 75: 878-884, 2004.
|
|
|
|
|
|
[PubMed: 15346351]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/425080]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kato, M., Patel, M. S., Levasseur, R., Lobov, I., Chang, B. H.-J., Glass, D. A., II, Hartmann, C., Li, L., Hwang, T.-H., Brayton, C. F., Lang, R. A., Karsenty, G., Chan, L.
|
|
<strong>Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor.</strong>
|
|
J. Cell Biol. 157: 303-314, 2002.
|
|
|
|
|
|
[PubMed: 11956231]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1083/jcb.200201089]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kondo, H., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K.
|
|
<strong>Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity.</strong>
|
|
Brit. J. Ophthal. 87: 1291-1295, 2003.
|
|
|
|
|
|
[PubMed: 14507768]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/bjo.87.10.1291]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Little, R. D., Carulli, J. P., Del Mastro, R. G., Dupuis, J., Osborne, M., Folz, C., Manning, S. P., Swain, P. M., Zhao, S.-C., Eustace, B., Lappe, M. M., Spitzer, L., and 23 others.
|
|
<strong>A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait.</strong>
|
|
Am. J. Hum. Genet. 70: 11-19, 2002.
|
|
|
|
|
|
[PubMed: 11741193]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/338450]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Magoori, K., Kang, M.-J., Ito, M. R., Kakuuchi, H., Ioka, R. X., Kamataki, A., Kim, D.-H., Asaba, H., Iwasaki, S., Takei, Y. A., Sasaki, M., Usui, S., Okazaki, M., Takahashi, S., Ono, M., Nose, M., Sakai, J., Fujino, T., Yamamoto, T. T.
|
|
<strong>Severe hypercholesterolemia, impaired fat tolerance, and advanced atherosclerosis in mice lacking both low density lipoprotein receptor-related protein 5 and apolipoprotein E.</strong>
|
|
J. Biol. Chem. 278: 11331-11336, 2003.
|
|
|
|
|
|
[PubMed: 12509421]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M211987200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mao, J., Wang, J., Liu, B., Pan, W., Farr, G. H., III, Flynn, C., Yuan, H., Takada, S., Kimelman, D., Li, L., Wu, D.
|
|
<strong>Low-density lipoprotein receptor-related protein-5 binds to axin and regulates the canonical Wnt signaling pathway.</strong>
|
|
Molec. Cell 7: 801-809, 2001.
|
|
|
|
|
|
[PubMed: 11336703]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s1097-2765(01)00224-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mizuguchi, T., Furuta, I., Watanabe, Y., Tsukamoto, K., Tomita, H., Tsujihata, M., Ohta, T., Kishino, T., Matsumoto, N., Minakami, H., Niikawa, N., Yoshiura, K.
|
|
<strong>LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant for bone mineral density.</strong>
|
|
J. Hum. Genet. 49: 80-86, 2004.
|
|
|
|
|
|
[PubMed: 14727154]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10038-003-0111-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Narumi, S., Numakura, C., Shiihara, T., Seiwa, C., Nozaki, Y., Yamagata, T., Momoi, M. Y., Watanabe, Y., Yoshino, M., Matsuishi, T., Nishi, E., Kawame, H., Akahane, T., Nishimura, G., Emi, M., Hasegawa, T.
|
|
<strong>Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma syndrome: identification of a 7.2-kb microdeletion using oligonucleotide tiling microarray.</strong>
|
|
Am. J. Med. Genet. 152A: 133-140, 2010.
|
|
|
|
|
|
[PubMed: 20034086]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.33177]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Price, S. M., Periam, N., Humphries, A., Woodruff, G., Trembath, R. C.
|
|
<strong>Familial exudative vitreoretinopathy linked to D11S533 in a large Asian family with consanguinity.</strong>
|
|
Ophthalmic Genet. 17: 53-57, 1996.
|
|
|
|
|
|
[PubMed: 8832721]
|
|
|
|
|
|
[Full Text: https://doi.org/10.3109/13816819609057871]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Qin, M., Hayashi, H., Oshima, K., Tahira, T., Hayashi, K., Kondo, H.
|
|
<strong>Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes.</strong>
|
|
Hum. Mutat. 26: 104-112, 2005.
|
|
|
|
|
|
[PubMed: 15981244]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20191]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Qin, M., Kondo, H., Tahira, T., Hayashi, K.
|
|
<strong>Moderate reduction of Norrin signaling activity associated with the causative missense mutations identified in patients with familial exudative vitreoretinopathy.</strong>
|
|
Hum. Genet. 122: 615-623, 2008.
|
|
|
|
|
|
[PubMed: 17955262]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00439-007-0438-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Renton,T., Odell, E., Drage, N. A.
|
|
<strong>Differential diagnosis and treatment of autosomal dominant osteosclerosis of the mandible.</strong>
|
|
Brit. J. Oral Maxillofac. Surg. 40: 55-59, 2002.
|
|
|
|
|
|
[PubMed: 11883972]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1054/bjom.2001.0719]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scopelliti, D., Orsini, R., Ventucci, D., Carratelli, D.
|
|
<strong>Malattia di Van Buchem.</strong>
|
|
Minerva Stomatol. 48: 227-234, 1999.
|
|
|
|
|
|
[PubMed: 10434540]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Semenov, M., Tamai, K., He, X.
|
|
<strong>SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor.</strong>
|
|
J. Biol. Chem. 280: 26770-26775, 2005.
|
|
|
|
|
|
[PubMed: 15908424]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M504308200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shastry, B. S., Trese, M. T.
|
|
<strong>Familial exudative vitreoretinopathy: further evidence for genetic heterogeneity. (Letter)</strong>
|
|
Am. J. Med. Genet. 69: 217-218, 1997.
|
|
|
|
|
|
[PubMed: 9056564]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1096-8628(19970317)69:2<217::aid-ajmg19>3.0.co;2-o]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Toomes, C., Bottomley, H. M., Jackson, R. M., Towns, K. V., Scott, S., Mackey, D. A., Craig, J. E., Jiang, L., Yang, Z., Trembath, R., Woodruff, G., Gregory-Evans, C. Y., Gregory-Evans, K., Parker, M. J., Black, G. C. M., Downey, L. M., Zhang, K., Inglehearn, C. F.
|
|
<strong>Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q.</strong>
|
|
Am. J. Hum. Genet. 74: 721-730, 2004.
|
|
|
|
|
|
[PubMed: 15024691]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/383202]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Twells, R. C. J., Mein, C. A., Phillips, M. S., Hess, J. F., Veijola, R., Gilbey, M., Bright, M., Metzker, M., Lie, B. A., Kingsnorth, A., Gregory, E., Nakagawa, Y., and 12 others.
|
|
<strong>Haplotype structure, LD blocks, and uneven recombination within the LRP5 gene.</strong>
|
|
Genome Res. 13: 845-855, 2003.
|
|
|
|
|
|
[PubMed: 12727905]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/gr.563703]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Twells, R. C. J., Metzker, M. L., Brown, S. D., Cox, R., Garey, C., Hammond, H., Hey, P. J., Levy, E., Nakagawa, Y., Philips, M. S., Todd, J. A., Hess, J. F.
|
|
<strong>The sequence and gene characterization of a 400-kb candidate region for IDDM4 on chromosome 11q13.</strong>
|
|
Genomics 72: 231-242, 2001.
|
|
|
|
|
|
[PubMed: 11401438]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.2000.6492]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Van Hul, E., Gram, J., Bollerslev, J., Van Wesenbeeck, L., Mathysen, E., Andersen, P. E., Vanhoenacker, F., Van Hul, W.
|
|
<strong>Localization of the gene causing autosomal dominant osteopetrosis type I to chromosome 11q12-13.</strong>
|
|
J. Bone Miner. Res. 17: 1111-1117, 2002.
|
|
|
|
|
|
[PubMed: 12054167]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1359/jbmr.2002.17.6.1111]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Van Wesenbeeck, L., Cleiren, E., Gram, J., Beals, R. K., Benichou, O., Scopelliti, D., Key, L., Renton, T., Bartels, C., Gong, Y., Warman, M. L., de Vernejoul, M.-C., Bollerslev, J., Van Hul, W.
|
|
<strong>Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density.</strong>
|
|
Am. J. Hum. Genet. 72: 763-771, 2003.
|
|
|
|
|
|
[PubMed: 12579474]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/368277]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Xia, W., Hu, J., Liu, F., Ma, J., Sun, S., Zhang, J., Jin, K., Huang, J., Jiang, N., Wang, X., Li, W., Ma, Z., Ma, D.
|
|
<strong>New role of LRP5, associated with nonsyndromic autosomal-recessive hereditary hearing loss.</strong>
|
|
Hum. Mutat. 38: 1421-1431, 2017. Note: Erratum: Hum. Mutat. 39: 882 only, 2018.
|
|
|
|
|
|
[PubMed: 28677207]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.23285]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yadav, V. K., Ryu, J.-H., Suda, N., Tanaka, K. F., Gingrich, J. A., Schutz, G., Glorieux, F. H., Chiang, C. Y., Zajac, J. D., Insogna, K. L., Mann, J. J., Hen, R., Ducy, P., Karsenty, G.
|
|
<strong>Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum.</strong>
|
|
Cell 135: 825-837, 2008.
|
|
|
|
|
|
[PubMed: 19041748]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2008.09.059]
|
|
|
|
|
|
</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">
|
|
Anne M. Stumpf - updated : 03/15/2023<br>Marla J. F. O'Neill - updated : 03/15/2023<br>Marla J. F. O'Neill - updated : 05/10/2021<br>Cassandra L. Kniffin - updated : 02/19/2018<br>Marla J. F. O'Neill - updated : 3/13/2013<br>Marla J. F. O'Neill - updated : 9/8/2011<br>Patricia A. Hartz - updated : 3/20/2009<br>Marla J. F. O'Neill - updated : 3/12/2008<br>Marla J. F. O'Neill - updated : 1/2/2008<br>Patricia A. Hartz - updated : 3/23/2007<br>Patricia A. Hartz - updated : 3/1/2007<br>Marla J. F. O'Neill - updated : 1/12/2007<br>Cassandra L. Kniffin - updated : 8/14/2006<br>Patricia A. Hartz - updated : 11/9/2005<br>Victor A. McKusick - updated : 10/14/2005<br>Patricia A. Hartz - updated : 9/1/2005<br>Victor A. McKusick - updated : 10/21/2004<br>Victor A. McKusick - updated : 4/27/2004<br>Victor A. McKusick - updated : 4/8/2004<br>Cassandra L. Kniffin - updated : 5/15/2003<br>Victor A. McKusick - updated : 2/28/2003<br>Victor A. McKusick - updated : 1/29/2003<br>Dawn Watkins-Chow - updated : 11/8/2002<br>Victor A. McKusick - updated : 6/7/2002<br>Deborah L. Stone - updated : 1/23/2002<br>Stylianos E. Antonarakis - updated : 11/20/2001<br>Stylianos E. Antonarakis - updated : 8/6/2001<br>Patti M. Sherman - updated : 5/10/1999<br>Sheryl A. Jankowski - updated : 4/12/1999
|
|
</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">
|
|
Sheryl A. Jankowski : 2/9/1999
|
|
</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">
|
|
carol : 09/09/2024<br>carol : 06/08/2023<br>carol : 04/28/2023<br>alopez : 03/24/2023<br>alopez : 03/21/2023<br>alopez : 03/15/2023<br>alopez : 03/15/2023<br>carol : 05/11/2021<br>carol : 05/10/2021<br>carol : 02/23/2018<br>carol : 02/22/2018<br>carol : 02/22/2018<br>carol : 02/21/2018<br>ckniffin : 02/19/2018<br>alopez : 07/15/2015<br>mcolton : 7/13/2015<br>carol : 4/3/2014<br>carol : 3/14/2013<br>terry : 3/13/2013<br>terry : 3/13/2013<br>carol : 9/8/2011<br>terry : 9/8/2011<br>mgross : 3/20/2009<br>terry : 3/20/2009<br>wwang : 3/17/2008<br>terry : 3/12/2008<br>carol : 1/18/2008<br>carol : 1/2/2008<br>carol : 10/3/2007<br>carol : 7/27/2007<br>mgross : 3/23/2007<br>mgross : 3/1/2007<br>carol : 1/17/2007<br>terry : 1/12/2007<br>wwang : 8/23/2006<br>ckniffin : 8/14/2006<br>terry : 3/22/2006<br>mgross : 12/1/2005<br>terry : 11/9/2005<br>alopez : 10/17/2005<br>terry : 10/14/2005<br>mgross : 9/7/2005<br>terry : 9/1/2005<br>alopez : 10/25/2004<br>terry : 10/21/2004<br>alopez : 4/28/2004<br>terry : 4/27/2004<br>tkritzer : 4/26/2004<br>tkritzer : 4/16/2004<br>terry : 4/8/2004<br>tkritzer : 3/22/2004<br>carol : 12/9/2003<br>cwells : 7/17/2003<br>terry : 7/9/2003<br>cwells : 5/21/2003<br>ckniffin : 5/15/2003<br>alopez : 3/19/2003<br>alopez : 3/19/2003<br>carol : 3/10/2003<br>tkritzer : 3/7/2003<br>tkritzer : 3/6/2003<br>terry : 2/28/2003<br>tkritzer : 1/31/2003<br>terry : 1/29/2003<br>tkritzer : 1/7/2003<br>carol : 11/8/2002<br>carol : 11/8/2002<br>terry : 6/7/2002<br>carol : 1/23/2002<br>carol : 1/23/2002<br>mgross : 11/20/2001<br>mgross : 11/20/2001<br>mgross : 8/6/2001<br>psherman : 5/24/1999<br>psherman : 5/17/1999<br>psherman : 5/10/1999<br>psherman : 4/12/1999<br>psherman : 2/9/1999
|
|
</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 14, 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>
|
|
|
|
|