3696 lines
280 KiB
Text
3696 lines
280 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
|
|
|
|
- #610698 - MACULAR DEGENERATION, AGE-RELATED, 4; ARMD4
|
|
|
|
|
|
- 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=610698"><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">#610698</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="/clinicalSynopsis/610698"><strong>Clinical Synopsis</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
|
|
<a href="/phenotypicSeries/PS603075"> <strong>Phenotypic Series</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="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://clinicaltrials.gov/search?cond=(MACULAR DEGENERATION, AGE-RELATED) OR (CFH)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.diseaseinfosearch.org/x/7654" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=610698[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="mimAnimalModels">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Animal Models</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.alliancegenome.org/disease/DOID:0110017" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.informatics.jax.org/disease/610698" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</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>DO:</strong> 0110017<br />
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
|
|
<span class="text-danger"><strong>#</strong></span>
|
|
610698
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
MACULAR DEGENERATION, AGE-RELATED, 4; ARMD4
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/1/1528?start=-3&limit=10&highlight=1528">
|
|
1q31.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
{Macular degeneration, age-related, 4}
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610698"> 610698 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
CFH
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/134370"> 134370 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/610698" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
|
|
<a href="/phenotypicSeries/PS603075" class="btn btn-info" role="button"> Phenotypic Series </a>
|
|
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/610698" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/610698" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Age-related macular degeneration <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267718000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267718000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H35.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H35.30</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/362.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">362.50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0242383&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0242383</a>]</span><br /> -
|
|
Progressive central visual loss <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5775310&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5775310</a>]</span><br /> -
|
|
Choroidal neovascularization <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0600518&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0600518</a>, <a href="https://bioportal.bioontology.org/search?q=C5574745&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5574745</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011506" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011506</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011506" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011506</a>]</span><br /> -
|
|
Geographic atrophy of retinal pigment epithelium (RPE) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5775311&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5775311</a>]</span><br /> -
|
|
'Starry sky' staining of ocular drusen seen on fluorescein angiogram <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5775312&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5775312</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Susceptibility conferred by mutation in the complement factor H gene (CFH, <a href="/entry/134370#0008">134370.0008</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Macular degeneration, age-related
|
|
- <a href="/phenotypicSeries/PS603075">PS603075</a>
|
|
- 20 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
|
|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/814?start=-3&limit=10&highlight=814"> 1p22.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/153800"> {Macular degeneration, age-related, 2} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/153800"> 153800 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601691"> ABCA4 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601691"> 601691 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/1502?start=-3&limit=10&highlight=1502"> 1q25.3-q31.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603075"> {Macular degeneration, age-related, 1} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603075"> 603075 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608548"> HMCN1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608548"> 608548 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/1528?start=-3&limit=10&highlight=1528"> 1q31.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610698"> {Macular degeneration, age-related, 4} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610698"> 610698 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/134370"> CFH </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/134370"> 134370 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/1529?start=-3&limit=10&highlight=1529"> 1q31.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603075"> {Macular degeneration, age-related, reduced risk of} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603075"> 603075 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605336"> CFHR3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605336"> 605336 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/1530?start=-3&limit=10&highlight=1530"> 1q31.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603075"> {Macular degeneration, age-related, reduced risk of} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603075"> 603075 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/134371"> CFHR1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/134371"> 134371 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/3/189?start=-3&limit=10&highlight=189"> 3p22.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613784"> {Macular degeneration, age-related, 12} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613784"> 613784 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601470"> CX3CR1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601470"> 601470 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/4/482?start=-3&limit=10&highlight=482"> 4q25 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615439"> {Macular degeneration, age-related, 13, susceptibility to} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615439"> 615439 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/217030"> CFI </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/217030"> 217030 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/5/126?start=-3&limit=10&highlight=126"> 5p13.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615591"> {Macular degeneration, age-related, 15, susceptibility to} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615591"> 615591 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/120940"> C9 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/120940"> 120940 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/6/342?start=-3&limit=10&highlight=342"> 6p21.33 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615489"> {Macular degeneration, age-related, 14, reduced risk of} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Digenic dominant">DD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615489"> 615489 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613927"> C2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613927"> 613927 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/6/343?start=-3&limit=10&highlight=343"> 6p21.33 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615489"> {Macular degeneration, age-related, 14, reduced risk of} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Digenic dominant">DD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615489"> 615489 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/138470"> CFB </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/138470"> 138470 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/9/416?start=-3&limit=10&highlight=416"> 9q32-q33 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611488"> Macular degeneration, age-related, 10 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="2 - The disorder was placed on the map by statistical methods"> 2 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611488"> 611488 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611488"> ARMD10 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611488"> 611488 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/10/190?start=-3&limit=10&highlight=190"> 10q11.23 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613761"> {Macular degeneration, age-related, susceptibility to, 5} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613761"> 613761 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609413"> ERCC6 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609413"> 609413 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/10/623?start=-3&limit=10&highlight=623"> 10q26.13 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613778"> {Macular degeneration, age-related, 8} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613778"> 613778 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611313"> LOC387715 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611313"> 611313 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/10/624?start=-3&limit=10&highlight=624"> 10q26.13 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610149"> {Macular degeneration, age-related, 7} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610149"> 610149 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602194"> HTRA1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602194"> 602194 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/10/624?start=-3&limit=10&highlight=624"> 10q26.13 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610149"> {Macular degeneration, age-related, neovascular type} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610149"> 610149 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602194"> HTRA1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602194"> 602194 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/14/464?start=-3&limit=10&highlight=464"> 14q32.12 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608895"> Macular degeneration, age-related, 3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608895"> 608895 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604580"> FBLN5 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604580"> 604580 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/19/117?start=-3&limit=10&highlight=117"> 19p13.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613757"> ?Macular degeneration, age-related, 6 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613757"> 613757 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610362"> RAX2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610362"> 610362 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/19/189?start=-3&limit=10&highlight=189"> 19p13.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611378"> {Macular degeneration, age-related, 9} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611378"> 611378 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/120700"> C3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/120700"> 120700 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/19/803?start=-3&limit=10&highlight=803"> 19q13.32 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603075"> {?Macular degeneration, age-related} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603075"> 603075 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/107741"> APOE </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/107741"> 107741 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/20/154?start=-3&limit=10&highlight=154"> 20p11.21 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611953"> {Macular degeneration, age-related, 11} </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611953"> 611953 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604312"> CST3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604312"> 604312 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="text-right small">
|
|
<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimTextFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because of evidence that susceptibility to age-related macular degeneration-4 (ARMD4) is conferred by variation in the CFH (<a href="/entry/134370">134370</a>) on chromosome 1q31.</p><p>For a phenotypic description and a discussion of genetic heterogeneity of age-related macular degeneration, see ARMD1 (<a href="/entry/603075">603075</a>).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>Age-related macular degeneration-4 (ARMD) is a disorder of the eye characterized by the formation of drusen on the retina, often as cuticular drusen which appear in a 'starry sky' distribution on fluorescein angiography. The disorder results in a progressive loss of central vision (summary by <a href="#7" class="mim-tip-reference" title="Hageman, G. S., Anderson, D. H., Johnson, L. V., Hancox, L. S., Taiber, A. J., Hardisty, L. I., Hageman, J. L., Stockman, H. A., Borchardt, J. D., Gehrs, K. M., Smith, R. J. H., Silvestri, G., and 15 others. <strong>A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration.</strong> Proc. Nat. Acad. Sci. 102: 7227-7232, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15870199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15870199</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15870199[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.0501536102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15870199">Hageman et al., 2005</a>, <a href="#6" class="mim-tip-reference" title="Grassi, M. A., Folk, J. C., Scheetz, T. E., Taylor, C. M., Sheffield, V. C., Stone, E. M. <strong>Complement factor H polymorphism p.tyr402his and cuticular drusen.</strong> Arch. Ophthal. 125: 93-97, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17210858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17210858</a>] [<a href="https://doi.org/10.1001/archopht.125.1.93" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17210858">Grassi et al., 2007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15870199+17210858" 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="#13" class="mim-tip-reference" title="Klein, R. J., Zeiss, C., Chew, E. Y., Tsai, J.-Y., Sackler, R. S., Haynes, C., Henning, A. K., SanGiovanni, J. P., Mane, S. M., Mayne, S. T., Bracken, M. B., Ferris, F. L., Ott, J., Barnstable, C., Hoh, J. <strong>Complement factor H polymorphism in age-related macular degeneration.</strong> Science 308: 385-389, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15761122/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15761122</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15761122[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/10.1126/science.1109557" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15761122">Klein et al. (2005)</a> performed a genomewide scan of 96 cases and 50 controls for polymorphisms associated with ARMD. They identified a risk allele (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs380390;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs380390</a>) with a p value of less than 10(-7) that increased the likelihood of ARMD by a factor of 7.4 in homozygous individuals (95% confidence interval 2.9 to 19). Resequencing revealed a polymorphism in linkage disequilibrium with the risk allele representing a tyr402-to-his substitution of complement factor H (Y402H; <a href="/entry/134370#0008">134370.0008</a>). This polymorphism is in a region of CFH that binds heparin and C-reactive protein (see <a href="/entry/123260">123260</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15761122" 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="Haines, J. L., Hauser, M. A., Schmidt, S., Scott, W. K., Olson, L. M., Gallins, P., Spencer, K. L., Kwan, S. Y., Noureddine, M., Gilbert, J. R., Schnetz-Boutaud, N., Agarwal, A., Postel, E. A., Pericak-Vance, M. A. <strong>Complement factor H variant increases the risk of age-related macular degeneration.</strong> Science 308: 419-421, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15761120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15761120</a>] [<a href="https://doi.org/10.1126/science.1110359" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15761120">Haines et al. (2005)</a> independently identified the CFH Y402H polymorphism in 2 independent data sets. They found that the Y402H variant significantly increased the risk for ARMD with odds ratios between 2.45 and 5.57. <a href="#8" class="mim-tip-reference" title="Haines, J. L., Hauser, M. A., Schmidt, S., Scott, W. K., Olson, L. M., Gallins, P., Spencer, K. L., Kwan, S. Y., Noureddine, M., Gilbert, J. R., Schnetz-Boutaud, N., Agarwal, A., Postel, E. A., Pericak-Vance, M. A. <strong>Complement factor H variant increases the risk of age-related macular degeneration.</strong> Science 308: 419-421, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15761120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15761120</a>] [<a href="https://doi.org/10.1126/science.1110359" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15761120">Haines et al. (2005)</a> suggested that this common variant likely explains about 43% of ARMD. <a href="#3" class="mim-tip-reference" title="Edwards, A. O., Ritter, R., III, Abel, K. J., Manning, A., Panhuysen, C., Farrer, L. A. <strong>Complement factor H polymorphism and age-related macular degeneration.</strong> Science 308: 421-424, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15761121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15761121</a>] [<a href="https://doi.org/10.1126/science.1110189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15761121">Edwards et al. (2005)</a> focused on the 1q25-q31 region, the ARMD1 locus, using 2 independent case-control populations. They found significant association (p = 4.95 x 10(-10)) with the CFH Y402H polymorphism. In their study, possession of at least 1 histidine at amino acid position 402 increased the risk of ARMD 2.7-fold, which they suggested may account for 50% of the attributable risk of ARMD. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15761120+15761121" 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="Hageman, G. S., Anderson, D. H., Johnson, L. V., Hancox, L. S., Taiber, A. J., Hardisty, L. I., Hageman, J. L., Stockman, H. A., Borchardt, J. D., Gehrs, K. M., Smith, R. J. H., Silvestri, G., and 15 others. <strong>A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration.</strong> Proc. Nat. Acad. Sci. 102: 7227-7232, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15870199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15870199</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15870199[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.0501536102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15870199">Hageman et al. (2005)</a> found a significant association between 2 variants in the CFH gene, Y402H and I62V (<a href="/entry/134370#0009">134370.0009</a>), and ARMD in 2 independent cohorts comprising over 900 cases of ARMD and 400 matched controls. One haplotype containing Y402H conferred an odds ratio of 2.46 and 3.51, when present in the heterozygous or homozygous state, respectively. Several protective haplotypes were also identified. <a href="#7" class="mim-tip-reference" title="Hageman, G. S., Anderson, D. H., Johnson, L. V., Hancox, L. S., Taiber, A. J., Hardisty, L. I., Hageman, J. L., Stockman, H. A., Borchardt, J. D., Gehrs, K. M., Smith, R. J. H., Silvestri, G., and 15 others. <strong>A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration.</strong> Proc. Nat. Acad. Sci. 102: 7227-7232, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15870199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15870199</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15870199[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.0501536102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15870199">Hageman et al. (2005)</a> found that CFH and its ligand C3b/iC3b colocalized in amyloid-containing substructural elements within macular drusen from patients with age-related macular degeneration. Real-time quantitative PCR assays showed that CFH gene products were generated from human retinal epithelial cells from individuals with and without macular degeneration. The findings suggested that variations within the CFH gene may attenuate complement inhibitory function and put retinal pigmented epithelial and choroidal cells at risk for alternative pathway-mediated complement attack. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15870199" 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="#2" class="mim-tip-reference" title="Conley, Y. P., Thalamuthu, A., Jakobsdottir, J., Weeks, D. E., Mah, T., Ferrell, R. E., Gorin, M. B. <strong>Candidate gene analysis suggests a role for fatty acid biosynthesis and regulation of the complement system in the etiology of age-related maculopathy.</strong> Hum. Molec. Genet. 14: 1991-2002, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15930014/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15930014</a>] [<a href="https://doi.org/10.1093/hmg/ddi204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15930014">Conley et al. (2005)</a> investigated 15 candidate genes for ARMD by performing family and case-control genetic association studies. The Y402H variant in exon 9 of the CFH gene was significantly associated with ARMD in the case-control allele (P less than 0.0001), case-control genotype (P less than 0.0001), and case-control family (P less than 0.0001) tests. They proposed a potential role for multiple pathways in the etiology of ARMD, including pathways involved with fatty acid biosynthesis and the complement system. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15930014" 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="Gotoh, N., Yamada, R., Hiratani, H., Renault, V., Kuroiwa, S., Monet, M., Toyoda, S., Chida, S., Mandai, M., Otani, A., Yoshimura, N., Matsuda, F. <strong>No association between complement factor H gene polymorphism and exudative age-related macular degeneration in Japanese.</strong> Hum. Genet. 120: 139-143, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16710702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16710702</a>] [<a href="https://doi.org/10.1007/s00439-006-0187-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16710702">Gotoh et al. (2006)</a> found no association between the Y402H polymorphism and exudative ARMD among 146 Japanese patients and 105 Japanese controls. There was also no association between ARMD and several CFH haplotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16710702" 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="#14" class="mim-tip-reference" title="Li, M., Atmaca-Sonmez, P., Othman, M., Branham, K. E. H., Khanna, R., Wade, M. S., Li, Y., Liang, L., Zareparsi, S., Swaroop, A., Abecasis, G. R. <strong>CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration.</strong> Nature Genet. 38: 1049-1054, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16936733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16936733</a>] [<a href="https://doi.org/10.1038/ng1871" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16936733">Li et al. (2006)</a> examined 84 polymorphisms in and around CFH in 726 affected individuals (including 544 unrelated individuals) and 268 unrelated controls. In this sample, 20 of these polymorphisms showed stronger association with disease susceptibility than did the Y402H variant (<a href="/entry/134370#0008">134370.0008</a>). Further, no single polymorphism could account for the contribution of the CFH locus to disease susceptibility. Instead, multiple polymorphisms defined a set of 4 common haplotypes (of which 2 were associated with disease susceptibility and 2 seemed to be protective) and multiple rare haplotypes (associated with increased susceptibility in aggregate). The results suggested that there are multiple disease susceptibility alleles in the region and that noncoding CFH variants play a role in disease susceptibility. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16936733" 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 case-control study drawn from a U.S.-based population of European descent, <a href="#15" class="mim-tip-reference" title="Maller, J., George, S., Purcell, S., Fagerness, J., Altshuler, D., Daly, M. J., Seddon, J. M. <strong>Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration.</strong> Nature Genet. 38: 1055-1059, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16936732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16936732</a>] [<a href="https://doi.org/10.1038/ng1873" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16936732">Maller et al. (2006)</a> identified a previously unrecognized common, noncoding variant in CFH (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1410996;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs1410996</a>; <a href="/entry/134370#0016">134370.0016</a>) that substantially increases the influence of this locus on ARMD. <a href="#14" class="mim-tip-reference" title="Li, M., Atmaca-Sonmez, P., Othman, M., Branham, K. E. H., Khanna, R., Wade, M. S., Li, Y., Liang, L., Zareparsi, S., Swaroop, A., Abecasis, G. R. <strong>CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration.</strong> Nature Genet. 38: 1049-1054, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16936733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16936733</a>] [<a href="https://doi.org/10.1038/ng1871" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16936733">Li et al. (2006)</a> also identified this variant in their study as the SNP showing the second strongest association with ARMD. In addition, <a href="#15" class="mim-tip-reference" title="Maller, J., George, S., Purcell, S., Fagerness, J., Altshuler, D., Daly, M. J., Seddon, J. M. <strong>Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration.</strong> Nature Genet. 38: 1055-1059, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16936732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16936732</a>] [<a href="https://doi.org/10.1038/ng1873" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16936732">Maller et al. (2006)</a> strongly replicated the associations of common alleles in the C2 (<a href="/entry/613927">613927</a>) and CFB (<a href="/entry/138470">138470</a>) genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16936733+16936732" 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 study of CFH and CFH-binding proteins in the retinal pigment epithelium (RPE)-choroid complex in individuals homozygous for either of the CFH Y402H isoforms (402YY or 402HH), <a href="#12" class="mim-tip-reference" title="Johnson, P. T., Betts, K. E., Radeke, M. J., Hageman, G. S., Anderson, D. H., Johnson, L. V. <strong>Individuals homozygous for the age-related macular degeneration risk-conferring variant of complement factor H have elevated levels of CRP in the choroid.</strong> Proc. Nat. Acad. Sci. 103: 17456-17461, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17079491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17079491</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17079491[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.0606234103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17079491">Johnson et al. (2006)</a> identified no significant differences in choroidal or drusen-associated CFH immunoreactivity in extramacular tissues between eyes with either of these isoforms. In contrast, at-risk individuals (402HH) had significantly higher levels of the CFH-binding protein C-reactive protein (CRP; <a href="/entry/123260">123260</a>) in the choroidal stroma. Quantitative immunoblot analysis demonstrated that the at-risk homozygotes had a 2.5-fold higher level of CRP in the RPE-choroid; no significant differences in CFH and complement component-5 (C5; <a href="/entry/120900">120900</a>) between isoforms were detected. Using quantitative real-time PCR, <a href="#12" class="mim-tip-reference" title="Johnson, P. T., Betts, K. E., Radeke, M. J., Hageman, G. S., Anderson, D. H., Johnson, L. V. <strong>Individuals homozygous for the age-related macular degeneration risk-conferring variant of complement factor H have elevated levels of CRP in the choroid.</strong> Proc. Nat. Acad. Sci. 103: 17456-17461, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17079491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17079491</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17079491[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.0606234103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17079491">Johnson et al. (2006)</a> found no differences in CFH transcription levels in the RPE-choroid, nor evidence of local ocular CRP transcription. The authors concluded that the elevated levels of CRP in CFH 402HH at-risk homozygotes may be evidence of chronic local inflammation and cellular injury in the RPE-choroid as a by-product of attenuated CFH complement-inhibitory activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17079491" 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 a population-based study among Latinos, <a href="#21" class="mim-tip-reference" title="Tedeschi-Blok, N., Buckley, J., Varma, R., Triche, T. J., Hinton, D. R. <strong>Population-based study of early age-related macular degeneration: role of the complement factor H Y402H polymorphism in bilateral but not unilateral disease.</strong> Ophthalmology 114: 99-103, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17198853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17198853</a>] [<a href="https://doi.org/10.1016/j.ophtha.2006.07.043" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17198853">Tedeschi-Blok et al. (2007)</a> found that the CFH Y402H polymorphism was not a major risk factor for overall early ARMD, but may play a role in susceptibility to bilateral early ARMD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17198853" 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="#20" class="mim-tip-reference" title="Scott, W. K., Schmidt, S., Hauser, M. A., Gallins, P., Schnetz-Boutaud, N., Spencer, K. L., Gilbert, J. R., Agarwal, A., Postel, E. A., Haines, J. L., Pericak-Vance, M. A. <strong>Independent effects of complement factor H Y402H polymorphism and cigarette smoking on risk of age-related macular degeneration.</strong> Ophthalmology 114: 1151-1156, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17241667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17241667</a>] [<a href="https://doi.org/10.1016/j.ophtha.2006.08.054" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17241667">Scott et al. (2007)</a> examined the potential gene-environment interaction between cigarette smoking and the CFH Y402H polymorphism, 2 strong risk factors for ARMD. Effects of both Y402H genotype and cigarette smoking were stronger when comparing neovascular (grade 5) ARMD with grade 1 controls than when comparing all cases (grades 3-5) with grades 1-2 controls. <a href="#20" class="mim-tip-reference" title="Scott, W. K., Schmidt, S., Hauser, M. A., Gallins, P., Schnetz-Boutaud, N., Spencer, K. L., Gilbert, J. R., Agarwal, A., Postel, E. A., Haines, J. L., Pericak-Vance, M. A. <strong>Independent effects of complement factor H Y402H polymorphism and cigarette smoking on risk of age-related macular degeneration.</strong> Ophthalmology 114: 1151-1156, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17241667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17241667</a>] [<a href="https://doi.org/10.1016/j.ophtha.2006.08.054" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17241667">Scott et al. (2007)</a> concluded that cigarette smoking and Y402H are independent risk factors for ARMD and that both risk factors are associated more strongly with neovascular (wet) ARMD than with all other forms of ARMD combined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17241667" 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="#6" class="mim-tip-reference" title="Grassi, M. A., Folk, J. C., Scheetz, T. E., Taylor, C. M., Sheffield, V. C., Stone, E. M. <strong>Complement factor H polymorphism p.tyr402his and cuticular drusen.</strong> Arch. Ophthal. 125: 93-97, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17210858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17210858</a>] [<a href="https://doi.org/10.1001/archopht.125.1.93" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17210858">Grassi et al. (2007)</a> found a higher association of the Y402H polymorphism with the cuticular drusen phenotype of ARMD than with more typical ARMD cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17210858" 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 case-control study with subjects originally recruited through the Cardiovascular Health Study (CHS) and the Age-Related Eye Disease Study (AREDS), <a href="#1" class="mim-tip-reference" title="Conley, Y. P., Jakobsdottir, J., Mah, T., Weeks, D. E., Klein, R., Kuller, L., Ferrell, R. E., Gorin, M. B. <strong>CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related maculopathy: AREDS and CHS cohorts and meta-analyses.</strong> Hum. Molec. Genet. 15: 3206-3218, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17000705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17000705</a>] [<a href="https://doi.org/10.1093/hmg/ddl396" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17000705">Conley et al. (2006)</a> found that CFH was significantly associated with ARMD in both cohorts (p less than 0.00001). A metaanalysis confirmed that the risk allele (Y402H) in the heterozygous or homozygous state (odds ratio = 2.4 and 6.2, respectively) conferred susceptibility. The LOC387715 gene (ARMS2; <a href="/entry/611313">611313</a>) was also significantly associated with ARMD in both cohorts (p less than 0.00001) and a metaanalysis confirmed that the risk allele (A69S; <a href="/entry/611313#0001">611313.0001</a>) in the heterozygous and homozygous state (odds ratio = 2.5 and 7.3, respectively) conferred susceptibility. Both CFH and LOC387715 showed an allele dosage effect on the ARMD risk: individuals homozygous at either locus were at more than 2-fold risk compared to those heterozygous. Joint action of CFH and LOC387715 was best described by independent multiplicative effect without significant interaction in both cohorts. Interaction of both genes with cigarette smoking was insignificant in both cohorts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17000705" 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="Thompson, C. L., Jun, G., Klein, B. E. K., Klein, R., Capriotti, J., Lee, K. E., Iyengar, S. K. <strong>Genetics of pigment changes and geographic atrophy.</strong> Invest. Ophthal. Vis. Sci. 48: 3005-3013, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17591865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17591865</a>] [<a href="https://doi.org/10.1167/iovs.06-1325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17591865">Thompson et al. (2007)</a> investigated the role of pigmentary abnormalities (PA) and geographic atrophy (GA) in ARMD. A previous genomewide scan was reanalyzed using the rate of change along the PA/GA scale. Evidence was found for linkage to 1q25, 5p13, 6q21-23, and 11q14 (p less than 0.01). The most significant peak was found on chromosome 1, near CFH (p = 6.20 x 10(-4)). Association analysis of CFH polymorphisms suggested that CFH might play a role in the development of pigmentary abnormalities and might modify the progression along the PA/GA scale. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17591865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Fritsche, L. G., Chen, W., Schu, M., Yaspan, B. L., Yu, Y., Thorleifsson, G., Zack, D. J., Arakawa, S., Cipriani, V., Ripke, S., Igo, R. P., Jr., Buitendijk, G. H. S., and 144 others. <strong>Seven new loci associated with age-related macular degeneration.</strong> Nature Genet. 45: 433-439, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23455636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23455636</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23455636[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/ng.2578" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23455636">Fritsche et al. (2013)</a> identified association of the A allele of <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs10737680;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs10737680</a> with increased risk of ARMD (OR 2.43; 95% CI 2.39-2.47; combined p = 1 x 10(-434)). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23455636" 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 an Amish ARMD family in which 3 affected sibs did not carry the common risk variants Y402H in CFH or A69S in ARMS2 <a href="#9" class="mim-tip-reference" title="Hoffman, J. D., Cooke Bailey, J. N., D'Aoust, L., Cade, W., Ayala-Haedo, J., Fuzzell, D., Laux, R., Adams, L. D., Reinhart-Mercer, L., Caywood, L., Whitehead-Gay, P., Agarwal, A., Wang, G., Scott, W. K., Pericak-Vance, M. A., Haines, J. L. <strong>Rare complement factor H variant associated with age-related macular degeneration in the Amish.</strong> Invest. Ophthal. Vis. Sci. 55: 4455-4460, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24906858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24906858</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24906858[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/10.1167/iovs.13-13684" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24906858">Hoffman et al. (2014)</a> performed exome sequencing and identified a missense mutation in the CFH gene, P503A (<a href="/entry/134370#0023">134370.0023</a>), in the 3 affected sibs. The oldest sib was diagnosed with bilateral choroidal neovascularization at 75 years of age, whereas the other 2 affected sibs were diagnosed with large drusen in both eyes at ages 72 and 68 years, respectively. A sib who was initially considered to be unaffected at age 66 years but who was later diagnosed with ARMD at age 74 did not carry the P503A variant; however, he did carry the known Y402H risk variant. One of 2 remaining unaffected sibs, who carried both the P503A and A69S risk variants, presented with small drusen upon examination at age 72 years. Case-control analysis using self-reported affection status in an Amish sample population showed significant association of ARMD with P503A (p = 9.27 x 10(-13)). This sample consisted of 1,150 individuals connected into a single 13-generation pedigree, including 128 individuals with ARMD, 728 without ARMD, and 294 with no information. Results were consistent in the subanalysis of individuals with clinically confirmed ARMD (p = 5.21 x 10(-7)). Carriers of the variant could be traced back 4 generations to a shared common ancestor, suggesting a recent founder event. The P503A variant was not found in a non-Amish Caucasian dataset consisting of 1,456 cases and 791 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24906858" 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>Interaction of CFH with Mutation in Other Genes</em></strong></p><p>
|
|
In a cohort of 460 advanced ARMD cases and 269 age-matched controls and 57 archived ARMD cases and 18 age-matched non-ARMD controls, <a href="#23" class="mim-tip-reference" title="Tuo, J., Ning, B., Bojanowski, C. M., Lin, Z.-N., Ross, R. J., Reed, G. F., Shen, D., Jiao, X., Zhou, M., Chew, E. Y., Kadlubar, F. F., Chan, C.-C. <strong>Synergic effect of polymorphisms in ERCC6 5-prime flanking region and complement factor H on age-related macular degeneration predisposition.</strong> Proc. Nat. Acad. Sci. 103: 9256-9261, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16754848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16754848</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16754848[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.0603485103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16754848">Tuo et al. (2006)</a> found that a -6530C-G SNP in the ERCC6 gene (<a href="/entry/609413#0010">609413.0010</a>) was associated with ARMD susceptibility, both independently and through interaction with an intronic G-C SNP in the CFH gene (<a href="/entry/134370#0008">134370.0008</a>) previously reported by <a href="#13" class="mim-tip-reference" title="Klein, R. J., Zeiss, C., Chew, E. Y., Tsai, J.-Y., Sackler, R. S., Haynes, C., Henning, A. K., SanGiovanni, J. P., Mane, S. M., Mayne, S. T., Bracken, M. B., Ferris, F. L., Ott, J., Barnstable, C., Hoh, J. <strong>Complement factor H polymorphism in age-related macular degeneration.</strong> Science 308: 385-389, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15761122/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15761122</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15761122[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/10.1126/science.1109557" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15761122">Klein et al. (2005)</a>. A disease odds ratio of 23 was conferred by homozygosity for risk alleles at both ERCC6 and CFH (G allele and C allele, respectively) compared to homozygosity for nonrisk alleles. <a href="#23" class="mim-tip-reference" title="Tuo, J., Ning, B., Bojanowski, C. M., Lin, Z.-N., Ross, R. J., Reed, G. F., Shen, D., Jiao, X., Zhou, M., Chew, E. Y., Kadlubar, F. F., Chan, C.-C. <strong>Synergic effect of polymorphisms in ERCC6 5-prime flanking region and complement factor H on age-related macular degeneration predisposition.</strong> Proc. Nat. Acad. Sci. 103: 9256-9261, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16754848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16754848</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16754848[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.0603485103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16754848">Tuo et al. (2006)</a> suggested that the strong ARMD predisposition conferred by the ERCC6 and CFH SNPs may result from biologic epistasis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16754848+15761122" 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="#11" class="mim-tip-reference" title="Hughes, A. E., Orr, N., Esfandiary, H., Diaz-Torres, M., Goodship T., Chakravarthy, U. <strong>A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration.</strong> Nature Genet. 38: 1173-1177, 2006. Note: Erratum: Nature Genet. 39: 567 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16998489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16998489</a>] [<a href="https://doi.org/10.1038/ng1890" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16998489">Hughes et al. (2006)</a> found that a haplotype carrying deletion of the CFHR1 (<a href="/entry/134371">134371</a>) and CFHR3 (<a href="/entry/605336">605336</a>) genes was associated with decreased risk of ARMD, being present on 20% of chromosomes of controls and 8% of chromosomes of individuals with ARMD. The proteins encoded by these genes were absent in serum of homozygotes. The protective effect of the deletion haplotype could not be attributed to linkage disequilibrium with Y402H (<a href="/entry/134370#0008">134370.0008</a>) and was replicated in an independent sample. The authors noted that the products of both the CFHR1 and CFHR3 genes are normally present in the circulation, where they have the potential to compete with CFH for C3 (<a href="/entry/120700">120700</a>) binding, and hypothesized that CFH produced from full-length transcript is beneficial and that other CFH-related proteins interfere with regulation of complement activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16998489" 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="#19" class="mim-tip-reference" title="Schaumberg, D. A., Hankinson, S. E., Guo, Q., Rimm, E., Hunter, D. J. <strong>A prospective study of 2 major age-related macular degeneration susceptibility alleles and interactions with modifiable risk factors.</strong> Arch. Ophthal. 125: 55-62, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17210852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17210852</a>] [<a href="https://doi.org/10.1001/archopht.125.1.55" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17210852">Schaumberg et al. (2007)</a> studied the associations between the CFH Y402H and the LOC387715 A69S (<a href="/entry/611313#0008">611313.0008</a>) variants with ARMD in a prospective, nested case-control study and investigated whether these variants interacted with modifiable risk factors. Participants with 1 or 2 copies of the Y402H variant were, respectively, 1.98 and 3.92 times more likely to develop ARMD, whereas the incidence rate ratios for 1 or 2 copies of A69S were 2.38 and 5.66, respectively. The fraction of ARMD cases attributable to these 2 variants was 63%. Subjects homozygous for both risk alleles had a 50-fold increased risk of ARMD, and cigarette smoking and obesity multiplied the risks associated with these variants. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17210852" 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="Meyers, K. J., Liu, Z., Millen, A. E., Iyengar, S. K., Blodi, B. A., Johnson, E., Snodderly, M., Klein, M. L., Gehrs, K. M., Tinker, L., Sarto, G. E., Robinson, J., Wallace, R. B., Mares, J. A. <strong>Joint associations of diet, lifestyle and genes with age-related macular degeneration.</strong> Ophthalmology 122: 2286-2294, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26354764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26354764</a>] [<a href="https://doi.org/10.1016/j.ophtha.2015.07.029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26354764">Meyers et al. (2015)</a> investigated whether the CFH Y402H allele or the ARMS2 A69S allele modified the risk for AMD in women with unhealthy lifestyles. They studied 1,663 women, aged 50 to 79 years, from the Carotenoids in Age-Related Eye Disease Study. Healthy lifestyle scores were assigned based on Healthy Eating Index scores, physical activity (metabolic equivalent of task hours/week), and smoking pack years. Odds of ARMD were 3.3 times greater in women with both low healthy lifestyle score (0-2/6) and high-risk CFH genotype (CC), relative to those with low genetic risk (TT) and high healthy lifestyle scores (4-6/6). There were no significant additive or multiplicative interactions for ARMS2 and lifestyle score. <a href="#16" class="mim-tip-reference" title="Meyers, K. J., Liu, Z., Millen, A. E., Iyengar, S. K., Blodi, B. A., Johnson, E., Snodderly, M., Klein, M. L., Gehrs, K. M., Tinker, L., Sarto, G. E., Robinson, J., Wallace, R. B., Mares, J. A. <strong>Joint associations of diet, lifestyle and genes with age-related macular degeneration.</strong> Ophthalmology 122: 2286-2294, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26354764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26354764</a>] [<a href="https://doi.org/10.1016/j.ophtha.2015.07.029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26354764">Meyers et al. (2015)</a> concluded that having unhealthy lifestyles and 2 CFH risk alleles increased ARMD risk (primarily in the early stages), in an additive or greater (synergistic) manner. However, unhealthy lifestyles increased ARMD risk regardless of ARMD risk genotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26354764" 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 711 individuals with ARMD and 1,041 controls, <a href="#18" class="mim-tip-reference" title="Raychaudhuri, S., Ripke, S., Li, M., Neale, B. M., Fagerness, J., Reynolds, R., Sobrin, L., Swaroop, A., Abecasis, G., Seddon, J. M., Daly, M. J. <strong>Associations of CFHR1-CFHR3 deletion and a CFH SNP to age-related macular degeneration are not independent. (Letter)</strong> Nature Genet. 42: 553-555, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20581873/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20581873</a>] [<a href="https://doi.org/10.1038/ng0710-553" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20581873">Raychaudhuri et al. (2010)</a> reproduced associations at the CFH Y402H allele, using <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs10801555;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs10801555</a> as a proxy, and CFH <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1410996;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs1410996</a>, using <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs10737680;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs10737680</a> as a proxy, but observed modest evidence for association with the CFHR1/CFHR3 deletion (p = 7.0 x 10(-21)). Logistic regression conditioned on <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs10737680;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs10737680</a> resulted in substantially mitigated statistical strength for the protective effect of the CFHR1/CFHR3 deletion, suggesting that the CFHR1/CFHR3 deletion and <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs10737680;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs10737680</a> were not entirely independent. Haplotype analysis demonstrated that both markers tagged a collection of low-risk haplotypes, but neither tagged all of them perfectly, suggesting that there could be 1 or more not-yet-identified variants that better explain disease risk. <a href="#18" class="mim-tip-reference" title="Raychaudhuri, S., Ripke, S., Li, M., Neale, B. M., Fagerness, J., Reynolds, R., Sobrin, L., Swaroop, A., Abecasis, G., Seddon, J. M., Daly, M. J. <strong>Associations of CFHR1-CFHR3 deletion and a CFH SNP to age-related macular degeneration are not independent. (Letter)</strong> Nature Genet. 42: 553-555, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20581873/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20581873</a>] [<a href="https://doi.org/10.1038/ng0710-553" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20581873">Raychaudhuri et al. (2010)</a> favored the parsimonious explanations of a single functional allele in high correlation with <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs10737680;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs10737680</a> acting on all protective haplotypes or of a risk variant acting on the intermediate risk haplotypes. In response, <a href="#10" class="mim-tip-reference" title="Hughes, A. E., Orr, N., Cordell, H. J., Goodship, T. <strong>Hughes et al. reply. (Letter)</strong> Nature Genet. 42: 555-556, 2010."None>Hughes et al. (2010)</a> noted that the finding of a lower statistical significance for the CFHR1/CFHR3 deletion than for <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs10801555;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs10801555</a> or <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs10737680;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs10737680</a> was a reflection of allele frequencies rather than effect size. The authors suggested that parsimonious explanations with the fewest functional elements are unnecessarily restrictive and noted that functional studies support a minimum of 3 factors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20581873" 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 identify rare penetrant variants in the CFH locus, <a href="#17" class="mim-tip-reference" title="Raychaudhuri, S., Iartchouk, O., Chin, K., Tan, P. L., Tai, A. K., Ripke, S., Gowrisankar, S., Vemuri, S., Montgomery, K., Yu, Y., Reynolds, R., Zack, D. J., Campochiaro, B., Campochiaro, P., Katsanis, N., Daly, M. J., Seddon, J. M. <strong>A rare penetrant mutation in CFH confers high risk of age-related macular degeneration.</strong> Nature Genet. 43: 1232-1236, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22019782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22019782</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22019782[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/ng.976" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22019782">Raychaudhuri et al. (2011)</a> phased genotypes for 20 common SNPs spanning the CFH-CFHR1-CFHR3 region and a common CFHR1-CFHR3 deletion in 711 individuals with advanced ARMD and 1,041 controls. They identified a rare high-risk haplotype ('H5') that lacked both the Y402H and <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs10737680;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs10737680</a>-<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1410996;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs1410996</a> risk alleles, but contained the R1210C substitution (<a href="/entry/134370#0017">134370.0017</a>). Genotyping R1210C in 2,423 ARMD cases and 1,122 controls demonstrated high penetrance (present in 40 cases vs 1 control; p = 7.0 x 10(-6)) and an association with a 6-year-earlier onset of disease (p = 2.3 x 10(-6)). Because R1210C is known to cause familial renal disease (atypical hemolytic uremic syndrome; <a href="/entry/235400">235400</a>), <a href="#17" class="mim-tip-reference" title="Raychaudhuri, S., Iartchouk, O., Chin, K., Tan, P. L., Tai, A. K., Ripke, S., Gowrisankar, S., Vemuri, S., Montgomery, K., Yu, Y., Reynolds, R., Zack, D. J., Campochiaro, B., Campochiaro, P., Katsanis, N., Daly, M. J., Seddon, J. M. <strong>A rare penetrant mutation in CFH confers high risk of age-related macular degeneration.</strong> Nature Genet. 43: 1232-1236, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22019782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22019782</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22019782[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/ng.976" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22019782">Raychaudhuri et al. (2011)</a> assessed renal function in 17 unrelated R1210C heterozygotes with advanced ARMD but found no evidence of clinically significant renal dysfunction, although subclinical renal dysfunction was present (median calculated GFR of 62 mL/min). As ARMD patients in general have subclinical renal dysfunction, the authors compared renal function in the R1210C heterozygotes to that of 17 ARMD patients without R1210C who were matched for disease severity, age, and gender, but found no significant difference. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22019782" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="references"class="mim-anchor"></a>
|
|
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Conley2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Conley, Y. P., Jakobsdottir, J., Mah, T., Weeks, D. E., Klein, R., Kuller, L., Ferrell, R. E., Gorin, M. B.
|
|
<strong>CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related maculopathy: AREDS and CHS cohorts and meta-analyses.</strong>
|
|
Hum. Molec. Genet. 15: 3206-3218, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17000705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17000705</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17000705" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddl396" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Conley2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Conley, Y. P., Thalamuthu, A., Jakobsdottir, J., Weeks, D. E., Mah, T., Ferrell, R. E., Gorin, M. B.
|
|
<strong>Candidate gene analysis suggests a role for fatty acid biosynthesis and regulation of the complement system in the etiology of age-related maculopathy.</strong>
|
|
Hum. Molec. Genet. 14: 1991-2002, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15930014/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15930014</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15930014" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddi204" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Edwards2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Edwards, A. O., Ritter, R., III, Abel, K. J., Manning, A., Panhuysen, C., Farrer, L. A.
|
|
<strong>Complement factor H polymorphism and age-related macular degeneration.</strong>
|
|
Science 308: 421-424, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15761121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15761121</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15761121" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1110189" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Fritsche2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fritsche, L. G., Chen, W., Schu, M., Yaspan, B. L., Yu, Y., Thorleifsson, G., Zack, D. J., Arakawa, S., Cipriani, V., Ripke, S., Igo, R. P., Jr., Buitendijk, G. H. S., and 144 others.
|
|
<strong>Seven new loci associated with age-related macular degeneration.</strong>
|
|
Nature Genet. 45: 433-439, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23455636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23455636</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23455636[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=23455636" 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/ng.2578" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Gotoh2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gotoh, N., Yamada, R., Hiratani, H., Renault, V., Kuroiwa, S., Monet, M., Toyoda, S., Chida, S., Mandai, M., Otani, A., Yoshimura, N., Matsuda, F.
|
|
<strong>No association between complement factor H gene polymorphism and exudative age-related macular degeneration in Japanese.</strong>
|
|
Hum. Genet. 120: 139-143, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16710702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16710702</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16710702" 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/s00439-006-0187-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Grassi2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Grassi, M. A., Folk, J. C., Scheetz, T. E., Taylor, C. M., Sheffield, V. C., Stone, E. M.
|
|
<strong>Complement factor H polymorphism p.tyr402his and cuticular drusen.</strong>
|
|
Arch. Ophthal. 125: 93-97, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17210858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17210858</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17210858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archopht.125.1.93" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Hageman2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hageman, G. S., Anderson, D. H., Johnson, L. V., Hancox, L. S., Taiber, A. J., Hardisty, L. I., Hageman, J. L., Stockman, H. A., Borchardt, J. D., Gehrs, K. M., Smith, R. J. H., Silvestri, G., and 15 others.
|
|
<strong>A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 7227-7232, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15870199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15870199</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15870199[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=15870199" 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.0501536102" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Haines2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Haines, J. L., Hauser, M. A., Schmidt, S., Scott, W. K., Olson, L. M., Gallins, P., Spencer, K. L., Kwan, S. Y., Noureddine, M., Gilbert, J. R., Schnetz-Boutaud, N., Agarwal, A., Postel, E. A., Pericak-Vance, M. A.
|
|
<strong>Complement factor H variant increases the risk of age-related macular degeneration.</strong>
|
|
Science 308: 419-421, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15761120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15761120</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15761120" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1110359" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Hoffman2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hoffman, J. D., Cooke Bailey, J. N., D'Aoust, L., Cade, W., Ayala-Haedo, J., Fuzzell, D., Laux, R., Adams, L. D., Reinhart-Mercer, L., Caywood, L., Whitehead-Gay, P., Agarwal, A., Wang, G., Scott, W. K., Pericak-Vance, M. A., Haines, J. L.
|
|
<strong>Rare complement factor H variant associated with age-related macular degeneration in the Amish.</strong>
|
|
Invest. Ophthal. Vis. Sci. 55: 4455-4460, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24906858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24906858</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24906858[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=24906858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1167/iovs.13-13684" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Hughes2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hughes, A. E., Orr, N., Cordell, H. J., Goodship, T.
|
|
<strong>Hughes et al. reply. (Letter)</strong>
|
|
Nature Genet. 42: 555-556, 2010.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Hughes2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hughes, A. E., Orr, N., Esfandiary, H., Diaz-Torres, M., Goodship T., Chakravarthy, U.
|
|
<strong>A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration.</strong>
|
|
Nature Genet. 38: 1173-1177, 2006. Note: Erratum: Nature Genet. 39: 567 only, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16998489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16998489</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16998489" 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/ng1890" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Johnson2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Johnson, P. T., Betts, K. E., Radeke, M. J., Hageman, G. S., Anderson, D. H., Johnson, L. V.
|
|
<strong>Individuals homozygous for the age-related macular degeneration risk-conferring variant of complement factor H have elevated levels of CRP in the choroid.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 17456-17461, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17079491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17079491</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17079491[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=17079491" 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.0606234103" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Klein2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Klein, R. J., Zeiss, C., Chew, E. Y., Tsai, J.-Y., Sackler, R. S., Haynes, C., Henning, A. K., SanGiovanni, J. P., Mane, S. M., Mayne, S. T., Bracken, M. B., Ferris, F. L., Ott, J., Barnstable, C., Hoh, J.
|
|
<strong>Complement factor H polymorphism in age-related macular degeneration.</strong>
|
|
Science 308: 385-389, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15761122/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15761122</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15761122[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=15761122" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1109557" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Li2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, M., Atmaca-Sonmez, P., Othman, M., Branham, K. E. H., Khanna, R., Wade, M. S., Li, Y., Liang, L., Zareparsi, S., Swaroop, A., Abecasis, G. R.
|
|
<strong>CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration.</strong>
|
|
Nature Genet. 38: 1049-1054, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16936733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16936733</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16936733" 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/ng1871" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Maller2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maller, J., George, S., Purcell, S., Fagerness, J., Altshuler, D., Daly, M. J., Seddon, J. M.
|
|
<strong>Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration.</strong>
|
|
Nature Genet. 38: 1055-1059, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16936732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16936732</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16936732" 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/ng1873" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Meyers2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meyers, K. J., Liu, Z., Millen, A. E., Iyengar, S. K., Blodi, B. A., Johnson, E., Snodderly, M., Klein, M. L., Gehrs, K. M., Tinker, L., Sarto, G. E., Robinson, J., Wallace, R. B., Mares, J. A.
|
|
<strong>Joint associations of diet, lifestyle and genes with age-related macular degeneration.</strong>
|
|
Ophthalmology 122: 2286-2294, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26354764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26354764</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26354764" 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.ophtha.2015.07.029" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Raychaudhuri2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Raychaudhuri, S., Iartchouk, O., Chin, K., Tan, P. L., Tai, A. K., Ripke, S., Gowrisankar, S., Vemuri, S., Montgomery, K., Yu, Y., Reynolds, R., Zack, D. J., Campochiaro, B., Campochiaro, P., Katsanis, N., Daly, M. J., Seddon, J. M.
|
|
<strong>A rare penetrant mutation in CFH confers high risk of age-related macular degeneration.</strong>
|
|
Nature Genet. 43: 1232-1236, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22019782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22019782</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22019782[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=22019782" 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/ng.976" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Raychaudhuri2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Raychaudhuri, S., Ripke, S., Li, M., Neale, B. M., Fagerness, J., Reynolds, R., Sobrin, L., Swaroop, A., Abecasis, G., Seddon, J. M., Daly, M. J.
|
|
<strong>Associations of CFHR1-CFHR3 deletion and a CFH SNP to age-related macular degeneration are not independent. (Letter)</strong>
|
|
Nature Genet. 42: 553-555, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20581873/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20581873</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20581873" 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/ng0710-553" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Schaumberg2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schaumberg, D. A., Hankinson, S. E., Guo, Q., Rimm, E., Hunter, D. J.
|
|
<strong>A prospective study of 2 major age-related macular degeneration susceptibility alleles and interactions with modifiable risk factors.</strong>
|
|
Arch. Ophthal. 125: 55-62, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17210852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17210852</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17210852" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archopht.125.1.55" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Scott2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Scott, W. K., Schmidt, S., Hauser, M. A., Gallins, P., Schnetz-Boutaud, N., Spencer, K. L., Gilbert, J. R., Agarwal, A., Postel, E. A., Haines, J. L., Pericak-Vance, M. A.
|
|
<strong>Independent effects of complement factor H Y402H polymorphism and cigarette smoking on risk of age-related macular degeneration.</strong>
|
|
Ophthalmology 114: 1151-1156, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17241667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17241667</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17241667" 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.ophtha.2006.08.054" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Tedeschi-Blok2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tedeschi-Blok, N., Buckley, J., Varma, R., Triche, T. J., Hinton, D. R.
|
|
<strong>Population-based study of early age-related macular degeneration: role of the complement factor H Y402H polymorphism in bilateral but not unilateral disease.</strong>
|
|
Ophthalmology 114: 99-103, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17198853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17198853</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17198853" 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.ophtha.2006.07.043" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Thompson2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thompson, C. L., Jun, G., Klein, B. E. K., Klein, R., Capriotti, J., Lee, K. E., Iyengar, S. K.
|
|
<strong>Genetics of pigment changes and geographic atrophy.</strong>
|
|
Invest. Ophthal. Vis. Sci. 48: 3005-3013, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17591865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17591865</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17591865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1167/iovs.06-1325" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Tuo2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tuo, J., Ning, B., Bojanowski, C. M., Lin, Z.-N., Ross, R. J., Reed, G. F., Shen, D., Jiao, X., Zhou, M., Chew, E. Y., Kadlubar, F. F., Chan, C.-C.
|
|
<strong>Synergic effect of polymorphisms in ERCC6 5-prime flanking region and complement factor H on age-related macular degeneration predisposition.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 9256-9261, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16754848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16754848</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16754848[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=16754848" 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.0603485103" 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">
|
|
Kelly A. Przylepa - updated : 09/26/2022
|
|
</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">
|
|
Jane Kelly - updated : 04/07/2016<br>Marla J. F. O'Neill - updated : 8/6/2014<br>Ada Hamosh - updated : 10/22/2013<br>Marla J. F. O'Neill - updated : 1/24/2012<br>Marla J. F. O'Neill - updated : 9/15/2010<br>George E. Tiller - updated : 11/18/2008<br>Jane Kelly - updated : 4/22/2008<br>Jane Kelly - updated : 11/29/2007<br>Jane Kelly - updated : 10/17/2007<br>Jane Kelly - updated : 10/15/2007<br>Jane Kelly - updated : 8/10/2007<br>Jane Kelly - updated : 3/23/2007
|
|
</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">
|
|
Anne M. Stumpf : 1/12/2007
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 09/26/2022
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 09/26/2022<br>carol : 04/07/2016<br>carol : 8/7/2014<br>mcolton : 8/6/2014<br>mcolton : 8/6/2014<br>alopez : 10/22/2013<br>alopez : 10/22/2013<br>carol : 2/26/2013<br>carol : 1/25/2012<br>terry : 1/24/2012<br>wwang : 9/15/2010<br>wwang : 11/18/2008<br>alopez : 10/20/2008<br>carol : 4/22/2008<br>carol : 11/29/2007<br>carol : 10/17/2007<br>carol : 10/16/2007<br>carol : 10/15/2007<br>carol : 8/10/2007<br>carol : 4/20/2007<br>carol : 3/23/2007<br>alopez : 1/12/2007
|
|
</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> 610698
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
MACULAR DEGENERATION, AGE-RELATED, 4; ARMD4
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
|
|
|
|
|
|
<strong>DO:</strong> 0110017;
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
1q31.3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
{Macular degeneration, age-related, 4}
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
610698
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
CFH
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
134370
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because of evidence that susceptibility to age-related macular degeneration-4 (ARMD4) is conferred by variation in the CFH (134370) on chromosome 1q31.</p><p>For a phenotypic description and a discussion of genetic heterogeneity of age-related macular degeneration, see ARMD1 (603075).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Age-related macular degeneration-4 (ARMD) is a disorder of the eye characterized by the formation of drusen on the retina, often as cuticular drusen which appear in a 'starry sky' distribution on fluorescein angiography. The disorder results in a progressive loss of central vision (summary by Hageman et al., 2005, Grassi et al., 2007). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Klein et al. (2005) performed a genomewide scan of 96 cases and 50 controls for polymorphisms associated with ARMD. They identified a risk allele (rs380390) with a p value of less than 10(-7) that increased the likelihood of ARMD by a factor of 7.4 in homozygous individuals (95% confidence interval 2.9 to 19). Resequencing revealed a polymorphism in linkage disequilibrium with the risk allele representing a tyr402-to-his substitution of complement factor H (Y402H; 134370.0008). This polymorphism is in a region of CFH that binds heparin and C-reactive protein (see 123260). </p><p>Haines et al. (2005) independently identified the CFH Y402H polymorphism in 2 independent data sets. They found that the Y402H variant significantly increased the risk for ARMD with odds ratios between 2.45 and 5.57. Haines et al. (2005) suggested that this common variant likely explains about 43% of ARMD. Edwards et al. (2005) focused on the 1q25-q31 region, the ARMD1 locus, using 2 independent case-control populations. They found significant association (p = 4.95 x 10(-10)) with the CFH Y402H polymorphism. In their study, possession of at least 1 histidine at amino acid position 402 increased the risk of ARMD 2.7-fold, which they suggested may account for 50% of the attributable risk of ARMD. </p><p>Hageman et al. (2005) found a significant association between 2 variants in the CFH gene, Y402H and I62V (134370.0009), and ARMD in 2 independent cohorts comprising over 900 cases of ARMD and 400 matched controls. One haplotype containing Y402H conferred an odds ratio of 2.46 and 3.51, when present in the heterozygous or homozygous state, respectively. Several protective haplotypes were also identified. Hageman et al. (2005) found that CFH and its ligand C3b/iC3b colocalized in amyloid-containing substructural elements within macular drusen from patients with age-related macular degeneration. Real-time quantitative PCR assays showed that CFH gene products were generated from human retinal epithelial cells from individuals with and without macular degeneration. The findings suggested that variations within the CFH gene may attenuate complement inhibitory function and put retinal pigmented epithelial and choroidal cells at risk for alternative pathway-mediated complement attack. </p><p>Conley et al. (2005) investigated 15 candidate genes for ARMD by performing family and case-control genetic association studies. The Y402H variant in exon 9 of the CFH gene was significantly associated with ARMD in the case-control allele (P less than 0.0001), case-control genotype (P less than 0.0001), and case-control family (P less than 0.0001) tests. They proposed a potential role for multiple pathways in the etiology of ARMD, including pathways involved with fatty acid biosynthesis and the complement system. </p><p>Gotoh et al. (2006) found no association between the Y402H polymorphism and exudative ARMD among 146 Japanese patients and 105 Japanese controls. There was also no association between ARMD and several CFH haplotypes. </p><p>Li et al. (2006) examined 84 polymorphisms in and around CFH in 726 affected individuals (including 544 unrelated individuals) and 268 unrelated controls. In this sample, 20 of these polymorphisms showed stronger association with disease susceptibility than did the Y402H variant (134370.0008). Further, no single polymorphism could account for the contribution of the CFH locus to disease susceptibility. Instead, multiple polymorphisms defined a set of 4 common haplotypes (of which 2 were associated with disease susceptibility and 2 seemed to be protective) and multiple rare haplotypes (associated with increased susceptibility in aggregate). The results suggested that there are multiple disease susceptibility alleles in the region and that noncoding CFH variants play a role in disease susceptibility. </p><p>In a case-control study drawn from a U.S.-based population of European descent, Maller et al. (2006) identified a previously unrecognized common, noncoding variant in CFH (rs1410996; 134370.0016) that substantially increases the influence of this locus on ARMD. Li et al. (2006) also identified this variant in their study as the SNP showing the second strongest association with ARMD. In addition, Maller et al. (2006) strongly replicated the associations of common alleles in the C2 (613927) and CFB (138470) genes. </p><p>In a study of CFH and CFH-binding proteins in the retinal pigment epithelium (RPE)-choroid complex in individuals homozygous for either of the CFH Y402H isoforms (402YY or 402HH), Johnson et al. (2006) identified no significant differences in choroidal or drusen-associated CFH immunoreactivity in extramacular tissues between eyes with either of these isoforms. In contrast, at-risk individuals (402HH) had significantly higher levels of the CFH-binding protein C-reactive protein (CRP; 123260) in the choroidal stroma. Quantitative immunoblot analysis demonstrated that the at-risk homozygotes had a 2.5-fold higher level of CRP in the RPE-choroid; no significant differences in CFH and complement component-5 (C5; 120900) between isoforms were detected. Using quantitative real-time PCR, Johnson et al. (2006) found no differences in CFH transcription levels in the RPE-choroid, nor evidence of local ocular CRP transcription. The authors concluded that the elevated levels of CRP in CFH 402HH at-risk homozygotes may be evidence of chronic local inflammation and cellular injury in the RPE-choroid as a by-product of attenuated CFH complement-inhibitory activity. </p><p>Using a population-based study among Latinos, Tedeschi-Blok et al. (2007) found that the CFH Y402H polymorphism was not a major risk factor for overall early ARMD, but may play a role in susceptibility to bilateral early ARMD. </p><p>Scott et al. (2007) examined the potential gene-environment interaction between cigarette smoking and the CFH Y402H polymorphism, 2 strong risk factors for ARMD. Effects of both Y402H genotype and cigarette smoking were stronger when comparing neovascular (grade 5) ARMD with grade 1 controls than when comparing all cases (grades 3-5) with grades 1-2 controls. Scott et al. (2007) concluded that cigarette smoking and Y402H are independent risk factors for ARMD and that both risk factors are associated more strongly with neovascular (wet) ARMD than with all other forms of ARMD combined. </p><p>Grassi et al. (2007) found a higher association of the Y402H polymorphism with the cuticular drusen phenotype of ARMD than with more typical ARMD cases. </p><p>In a case-control study with subjects originally recruited through the Cardiovascular Health Study (CHS) and the Age-Related Eye Disease Study (AREDS), Conley et al. (2006) found that CFH was significantly associated with ARMD in both cohorts (p less than 0.00001). A metaanalysis confirmed that the risk allele (Y402H) in the heterozygous or homozygous state (odds ratio = 2.4 and 6.2, respectively) conferred susceptibility. The LOC387715 gene (ARMS2; 611313) was also significantly associated with ARMD in both cohorts (p less than 0.00001) and a metaanalysis confirmed that the risk allele (A69S; 611313.0001) in the heterozygous and homozygous state (odds ratio = 2.5 and 7.3, respectively) conferred susceptibility. Both CFH and LOC387715 showed an allele dosage effect on the ARMD risk: individuals homozygous at either locus were at more than 2-fold risk compared to those heterozygous. Joint action of CFH and LOC387715 was best described by independent multiplicative effect without significant interaction in both cohorts. Interaction of both genes with cigarette smoking was insignificant in both cohorts. </p><p>Thompson et al. (2007) investigated the role of pigmentary abnormalities (PA) and geographic atrophy (GA) in ARMD. A previous genomewide scan was reanalyzed using the rate of change along the PA/GA scale. Evidence was found for linkage to 1q25, 5p13, 6q21-23, and 11q14 (p less than 0.01). The most significant peak was found on chromosome 1, near CFH (p = 6.20 x 10(-4)). Association analysis of CFH polymorphisms suggested that CFH might play a role in the development of pigmentary abnormalities and might modify the progression along the PA/GA scale. </p><p>Fritsche et al. (2013) identified association of the A allele of rs10737680 with increased risk of ARMD (OR 2.43; 95% CI 2.39-2.47; combined p = 1 x 10(-434)). </p><p>In an Amish ARMD family in which 3 affected sibs did not carry the common risk variants Y402H in CFH or A69S in ARMS2 Hoffman et al. (2014) performed exome sequencing and identified a missense mutation in the CFH gene, P503A (134370.0023), in the 3 affected sibs. The oldest sib was diagnosed with bilateral choroidal neovascularization at 75 years of age, whereas the other 2 affected sibs were diagnosed with large drusen in both eyes at ages 72 and 68 years, respectively. A sib who was initially considered to be unaffected at age 66 years but who was later diagnosed with ARMD at age 74 did not carry the P503A variant; however, he did carry the known Y402H risk variant. One of 2 remaining unaffected sibs, who carried both the P503A and A69S risk variants, presented with small drusen upon examination at age 72 years. Case-control analysis using self-reported affection status in an Amish sample population showed significant association of ARMD with P503A (p = 9.27 x 10(-13)). This sample consisted of 1,150 individuals connected into a single 13-generation pedigree, including 128 individuals with ARMD, 728 without ARMD, and 294 with no information. Results were consistent in the subanalysis of individuals with clinically confirmed ARMD (p = 5.21 x 10(-7)). Carriers of the variant could be traced back 4 generations to a shared common ancestor, suggesting a recent founder event. The P503A variant was not found in a non-Amish Caucasian dataset consisting of 1,456 cases and 791 controls. </p><p><strong><em>Interaction of CFH with Mutation in Other Genes</em></strong></p><p>
|
|
In a cohort of 460 advanced ARMD cases and 269 age-matched controls and 57 archived ARMD cases and 18 age-matched non-ARMD controls, Tuo et al. (2006) found that a -6530C-G SNP in the ERCC6 gene (609413.0010) was associated with ARMD susceptibility, both independently and through interaction with an intronic G-C SNP in the CFH gene (134370.0008) previously reported by Klein et al. (2005). A disease odds ratio of 23 was conferred by homozygosity for risk alleles at both ERCC6 and CFH (G allele and C allele, respectively) compared to homozygosity for nonrisk alleles. Tuo et al. (2006) suggested that the strong ARMD predisposition conferred by the ERCC6 and CFH SNPs may result from biologic epistasis. </p><p>Hughes et al. (2006) found that a haplotype carrying deletion of the CFHR1 (134371) and CFHR3 (605336) genes was associated with decreased risk of ARMD, being present on 20% of chromosomes of controls and 8% of chromosomes of individuals with ARMD. The proteins encoded by these genes were absent in serum of homozygotes. The protective effect of the deletion haplotype could not be attributed to linkage disequilibrium with Y402H (134370.0008) and was replicated in an independent sample. The authors noted that the products of both the CFHR1 and CFHR3 genes are normally present in the circulation, where they have the potential to compete with CFH for C3 (120700) binding, and hypothesized that CFH produced from full-length transcript is beneficial and that other CFH-related proteins interfere with regulation of complement activity. </p><p>Schaumberg et al. (2007) studied the associations between the CFH Y402H and the LOC387715 A69S (611313.0008) variants with ARMD in a prospective, nested case-control study and investigated whether these variants interacted with modifiable risk factors. Participants with 1 or 2 copies of the Y402H variant were, respectively, 1.98 and 3.92 times more likely to develop ARMD, whereas the incidence rate ratios for 1 or 2 copies of A69S were 2.38 and 5.66, respectively. The fraction of ARMD cases attributable to these 2 variants was 63%. Subjects homozygous for both risk alleles had a 50-fold increased risk of ARMD, and cigarette smoking and obesity multiplied the risks associated with these variants. </p><p>Meyers et al. (2015) investigated whether the CFH Y402H allele or the ARMS2 A69S allele modified the risk for AMD in women with unhealthy lifestyles. They studied 1,663 women, aged 50 to 79 years, from the Carotenoids in Age-Related Eye Disease Study. Healthy lifestyle scores were assigned based on Healthy Eating Index scores, physical activity (metabolic equivalent of task hours/week), and smoking pack years. Odds of ARMD were 3.3 times greater in women with both low healthy lifestyle score (0-2/6) and high-risk CFH genotype (CC), relative to those with low genetic risk (TT) and high healthy lifestyle scores (4-6/6). There were no significant additive or multiplicative interactions for ARMS2 and lifestyle score. Meyers et al. (2015) concluded that having unhealthy lifestyles and 2 CFH risk alleles increased ARMD risk (primarily in the early stages), in an additive or greater (synergistic) manner. However, unhealthy lifestyles increased ARMD risk regardless of ARMD risk genotype. </p><p>In 711 individuals with ARMD and 1,041 controls, Raychaudhuri et al. (2010) reproduced associations at the CFH Y402H allele, using rs10801555 as a proxy, and CFH rs1410996, using rs10737680 as a proxy, but observed modest evidence for association with the CFHR1/CFHR3 deletion (p = 7.0 x 10(-21)). Logistic regression conditioned on rs10737680 resulted in substantially mitigated statistical strength for the protective effect of the CFHR1/CFHR3 deletion, suggesting that the CFHR1/CFHR3 deletion and rs10737680 were not entirely independent. Haplotype analysis demonstrated that both markers tagged a collection of low-risk haplotypes, but neither tagged all of them perfectly, suggesting that there could be 1 or more not-yet-identified variants that better explain disease risk. Raychaudhuri et al. (2010) favored the parsimonious explanations of a single functional allele in high correlation with rs10737680 acting on all protective haplotypes or of a risk variant acting on the intermediate risk haplotypes. In response, Hughes et al. (2010) noted that the finding of a lower statistical significance for the CFHR1/CFHR3 deletion than for rs10801555 or rs10737680 was a reflection of allele frequencies rather than effect size. The authors suggested that parsimonious explanations with the fewest functional elements are unnecessarily restrictive and noted that functional studies support a minimum of 3 factors. </p><p>To identify rare penetrant variants in the CFH locus, Raychaudhuri et al. (2011) phased genotypes for 20 common SNPs spanning the CFH-CFHR1-CFHR3 region and a common CFHR1-CFHR3 deletion in 711 individuals with advanced ARMD and 1,041 controls. They identified a rare high-risk haplotype ('H5') that lacked both the Y402H and rs10737680-rs1410996 risk alleles, but contained the R1210C substitution (134370.0017). Genotyping R1210C in 2,423 ARMD cases and 1,122 controls demonstrated high penetrance (present in 40 cases vs 1 control; p = 7.0 x 10(-6)) and an association with a 6-year-earlier onset of disease (p = 2.3 x 10(-6)). Because R1210C is known to cause familial renal disease (atypical hemolytic uremic syndrome; 235400), Raychaudhuri et al. (2011) assessed renal function in 17 unrelated R1210C heterozygotes with advanced ARMD but found no evidence of clinically significant renal dysfunction, although subclinical renal dysfunction was present (median calculated GFR of 62 mL/min). As ARMD patients in general have subclinical renal dysfunction, the authors compared renal function in the R1210C heterozygotes to that of 17 ARMD patients without R1210C who were matched for disease severity, age, and gender, but found no significant difference. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Conley, Y. P., Jakobsdottir, J., Mah, T., Weeks, D. E., Klein, R., Kuller, L., Ferrell, R. E., Gorin, M. B.
|
|
<strong>CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related maculopathy: AREDS and CHS cohorts and meta-analyses.</strong>
|
|
Hum. Molec. Genet. 15: 3206-3218, 2006.
|
|
|
|
|
|
[PubMed: 17000705]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddl396]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Conley, Y. P., Thalamuthu, A., Jakobsdottir, J., Weeks, D. E., Mah, T., Ferrell, R. E., Gorin, M. B.
|
|
<strong>Candidate gene analysis suggests a role for fatty acid biosynthesis and regulation of the complement system in the etiology of age-related maculopathy.</strong>
|
|
Hum. Molec. Genet. 14: 1991-2002, 2005.
|
|
|
|
|
|
[PubMed: 15930014]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi204]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Edwards, A. O., Ritter, R., III, Abel, K. J., Manning, A., Panhuysen, C., Farrer, L. A.
|
|
<strong>Complement factor H polymorphism and age-related macular degeneration.</strong>
|
|
Science 308: 421-424, 2005.
|
|
|
|
|
|
[PubMed: 15761121]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1110189]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fritsche, L. G., Chen, W., Schu, M., Yaspan, B. L., Yu, Y., Thorleifsson, G., Zack, D. J., Arakawa, S., Cipriani, V., Ripke, S., Igo, R. P., Jr., Buitendijk, G. H. S., and 144 others.
|
|
<strong>Seven new loci associated with age-related macular degeneration.</strong>
|
|
Nature Genet. 45: 433-439, 2013.
|
|
|
|
|
|
[PubMed: 23455636]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.2578]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gotoh, N., Yamada, R., Hiratani, H., Renault, V., Kuroiwa, S., Monet, M., Toyoda, S., Chida, S., Mandai, M., Otani, A., Yoshimura, N., Matsuda, F.
|
|
<strong>No association between complement factor H gene polymorphism and exudative age-related macular degeneration in Japanese.</strong>
|
|
Hum. Genet. 120: 139-143, 2006.
|
|
|
|
|
|
[PubMed: 16710702]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00439-006-0187-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Grassi, M. A., Folk, J. C., Scheetz, T. E., Taylor, C. M., Sheffield, V. C., Stone, E. M.
|
|
<strong>Complement factor H polymorphism p.tyr402his and cuticular drusen.</strong>
|
|
Arch. Ophthal. 125: 93-97, 2007.
|
|
|
|
|
|
[PubMed: 17210858]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archopht.125.1.93]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hageman, G. S., Anderson, D. H., Johnson, L. V., Hancox, L. S., Taiber, A. J., Hardisty, L. I., Hageman, J. L., Stockman, H. A., Borchardt, J. D., Gehrs, K. M., Smith, R. J. H., Silvestri, G., and 15 others.
|
|
<strong>A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 7227-7232, 2005.
|
|
|
|
|
|
[PubMed: 15870199]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0501536102]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Haines, J. L., Hauser, M. A., Schmidt, S., Scott, W. K., Olson, L. M., Gallins, P., Spencer, K. L., Kwan, S. Y., Noureddine, M., Gilbert, J. R., Schnetz-Boutaud, N., Agarwal, A., Postel, E. A., Pericak-Vance, M. A.
|
|
<strong>Complement factor H variant increases the risk of age-related macular degeneration.</strong>
|
|
Science 308: 419-421, 2005.
|
|
|
|
|
|
[PubMed: 15761120]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1110359]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hoffman, J. D., Cooke Bailey, J. N., D'Aoust, L., Cade, W., Ayala-Haedo, J., Fuzzell, D., Laux, R., Adams, L. D., Reinhart-Mercer, L., Caywood, L., Whitehead-Gay, P., Agarwal, A., Wang, G., Scott, W. K., Pericak-Vance, M. A., Haines, J. L.
|
|
<strong>Rare complement factor H variant associated with age-related macular degeneration in the Amish.</strong>
|
|
Invest. Ophthal. Vis. Sci. 55: 4455-4460, 2014.
|
|
|
|
|
|
[PubMed: 24906858]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1167/iovs.13-13684]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hughes, A. E., Orr, N., Cordell, H. J., Goodship, T.
|
|
<strong>Hughes et al. reply. (Letter)</strong>
|
|
Nature Genet. 42: 555-556, 2010.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hughes, A. E., Orr, N., Esfandiary, H., Diaz-Torres, M., Goodship T., Chakravarthy, U.
|
|
<strong>A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration.</strong>
|
|
Nature Genet. 38: 1173-1177, 2006. Note: Erratum: Nature Genet. 39: 567 only, 2007.
|
|
|
|
|
|
[PubMed: 16998489]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1890]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johnson, P. T., Betts, K. E., Radeke, M. J., Hageman, G. S., Anderson, D. H., Johnson, L. V.
|
|
<strong>Individuals homozygous for the age-related macular degeneration risk-conferring variant of complement factor H have elevated levels of CRP in the choroid.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 17456-17461, 2006.
|
|
|
|
|
|
[PubMed: 17079491]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0606234103]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Klein, R. J., Zeiss, C., Chew, E. Y., Tsai, J.-Y., Sackler, R. S., Haynes, C., Henning, A. K., SanGiovanni, J. P., Mane, S. M., Mayne, S. T., Bracken, M. B., Ferris, F. L., Ott, J., Barnstable, C., Hoh, J.
|
|
<strong>Complement factor H polymorphism in age-related macular degeneration.</strong>
|
|
Science 308: 385-389, 2005.
|
|
|
|
|
|
[PubMed: 15761122]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1109557]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Li, M., Atmaca-Sonmez, P., Othman, M., Branham, K. E. H., Khanna, R., Wade, M. S., Li, Y., Liang, L., Zareparsi, S., Swaroop, A., Abecasis, G. R.
|
|
<strong>CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration.</strong>
|
|
Nature Genet. 38: 1049-1054, 2006.
|
|
|
|
|
|
[PubMed: 16936733]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1871]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maller, J., George, S., Purcell, S., Fagerness, J., Altshuler, D., Daly, M. J., Seddon, J. M.
|
|
<strong>Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration.</strong>
|
|
Nature Genet. 38: 1055-1059, 2006.
|
|
|
|
|
|
[PubMed: 16936732]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1873]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meyers, K. J., Liu, Z., Millen, A. E., Iyengar, S. K., Blodi, B. A., Johnson, E., Snodderly, M., Klein, M. L., Gehrs, K. M., Tinker, L., Sarto, G. E., Robinson, J., Wallace, R. B., Mares, J. A.
|
|
<strong>Joint associations of diet, lifestyle and genes with age-related macular degeneration.</strong>
|
|
Ophthalmology 122: 2286-2294, 2015.
|
|
|
|
|
|
[PubMed: 26354764]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ophtha.2015.07.029]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Raychaudhuri, S., Iartchouk, O., Chin, K., Tan, P. L., Tai, A. K., Ripke, S., Gowrisankar, S., Vemuri, S., Montgomery, K., Yu, Y., Reynolds, R., Zack, D. J., Campochiaro, B., Campochiaro, P., Katsanis, N., Daly, M. J., Seddon, J. M.
|
|
<strong>A rare penetrant mutation in CFH confers high risk of age-related macular degeneration.</strong>
|
|
Nature Genet. 43: 1232-1236, 2011.
|
|
|
|
|
|
[PubMed: 22019782]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.976]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Raychaudhuri, S., Ripke, S., Li, M., Neale, B. M., Fagerness, J., Reynolds, R., Sobrin, L., Swaroop, A., Abecasis, G., Seddon, J. M., Daly, M. J.
|
|
<strong>Associations of CFHR1-CFHR3 deletion and a CFH SNP to age-related macular degeneration are not independent. (Letter)</strong>
|
|
Nature Genet. 42: 553-555, 2010.
|
|
|
|
|
|
[PubMed: 20581873]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0710-553]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schaumberg, D. A., Hankinson, S. E., Guo, Q., Rimm, E., Hunter, D. J.
|
|
<strong>A prospective study of 2 major age-related macular degeneration susceptibility alleles and interactions with modifiable risk factors.</strong>
|
|
Arch. Ophthal. 125: 55-62, 2007.
|
|
|
|
|
|
[PubMed: 17210852]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archopht.125.1.55]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scott, W. K., Schmidt, S., Hauser, M. A., Gallins, P., Schnetz-Boutaud, N., Spencer, K. L., Gilbert, J. R., Agarwal, A., Postel, E. A., Haines, J. L., Pericak-Vance, M. A.
|
|
<strong>Independent effects of complement factor H Y402H polymorphism and cigarette smoking on risk of age-related macular degeneration.</strong>
|
|
Ophthalmology 114: 1151-1156, 2007.
|
|
|
|
|
|
[PubMed: 17241667]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ophtha.2006.08.054]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tedeschi-Blok, N., Buckley, J., Varma, R., Triche, T. J., Hinton, D. R.
|
|
<strong>Population-based study of early age-related macular degeneration: role of the complement factor H Y402H polymorphism in bilateral but not unilateral disease.</strong>
|
|
Ophthalmology 114: 99-103, 2007.
|
|
|
|
|
|
[PubMed: 17198853]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ophtha.2006.07.043]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thompson, C. L., Jun, G., Klein, B. E. K., Klein, R., Capriotti, J., Lee, K. E., Iyengar, S. K.
|
|
<strong>Genetics of pigment changes and geographic atrophy.</strong>
|
|
Invest. Ophthal. Vis. Sci. 48: 3005-3013, 2007.
|
|
|
|
|
|
[PubMed: 17591865]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1167/iovs.06-1325]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tuo, J., Ning, B., Bojanowski, C. M., Lin, Z.-N., Ross, R. J., Reed, G. F., Shen, D., Jiao, X., Zhou, M., Chew, E. Y., Kadlubar, F. F., Chan, C.-C.
|
|
<strong>Synergic effect of polymorphisms in ERCC6 5-prime flanking region and complement factor H on age-related macular degeneration predisposition.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 9256-9261, 2006.
|
|
|
|
|
|
[PubMed: 16754848]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0603485103]
|
|
|
|
|
|
</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">
|
|
Kelly A. Przylepa - updated : 09/26/2022<br>Jane Kelly - updated : 04/07/2016<br>Marla J. F. O'Neill - updated : 8/6/2014<br>Ada Hamosh - updated : 10/22/2013<br>Marla J. F. O'Neill - updated : 1/24/2012<br>Marla J. F. O'Neill - updated : 9/15/2010<br>George E. Tiller - updated : 11/18/2008<br>Jane Kelly - updated : 4/22/2008<br>Jane Kelly - updated : 11/29/2007<br>Jane Kelly - updated : 10/17/2007<br>Jane Kelly - updated : 10/15/2007<br>Jane Kelly - updated : 8/10/2007<br>Jane Kelly - updated : 3/23/2007
|
|
</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">
|
|
Anne M. Stumpf : 1/12/2007
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 09/26/2022<br>alopez : 09/26/2022<br>carol : 04/07/2016<br>carol : 8/7/2014<br>mcolton : 8/6/2014<br>mcolton : 8/6/2014<br>alopez : 10/22/2013<br>alopez : 10/22/2013<br>carol : 2/26/2013<br>carol : 1/25/2012<br>terry : 1/24/2012<br>wwang : 9/15/2010<br>wwang : 11/18/2008<br>alopez : 10/20/2008<br>carol : 4/22/2008<br>carol : 11/29/2007<br>carol : 10/17/2007<br>carol : 10/16/2007<br>carol : 10/15/2007<br>carol : 8/10/2007<br>carol : 4/20/2007<br>carol : 3/23/2007<br>alopez : 1/12/2007
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div id="mimFooter">
|
|
|
|
|
|
<div class="container ">
|
|
<div class="row">
|
|
<br />
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="hidden-print mim-footer">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="visible-print-block mim-footer" style="position: relative;">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
<br />
|
|
Printed: March 13, 2025
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
|
|
<div class="modal-dialog" role="document">
|
|
<div class="modal-content">
|
|
<div class="modal-header">
|
|
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">×</span></button>
|
|
<h4 class="modal-title" id="mimDonationPopupModalTitle">
|
|
OMIM Donation:
|
|
</h4>
|
|
</div>
|
|
<div class="modal-body">
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Dear OMIM User,
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
To ensure long-term funding for the OMIM project, we have diversified
|
|
our revenue stream. We are determined to keep this website freely
|
|
accessible. Unfortunately, it is not free to produce. Expert curators
|
|
review the literature and organize it to facilitate your work. Over 90%
|
|
of the OMIM's operating expenses go to salary support for MD and PhD
|
|
science writers and biocurators. Please join your colleagues by making a
|
|
donation now and again in the future. Donations are an important
|
|
component of our efforts to ensure long-term funding to provide you the
|
|
information that you need at your fingertips.
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Thank you in advance for your generous support, <br />
|
|
Ada Hamosh, MD, MPH <br />
|
|
Scientific Director, OMIM <br />
|
|
</p>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div class="modal-footer">
|
|
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
</body>
|
|
|
|
</html>
|
|
|
|
|