4702 lines
399 KiB
Text
4702 lines
399 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
|
|
|
|
- #165500 - OPTIC ATROPHY 1; OPA1
|
|
|
|
|
|
- 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=165500"><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">#165500</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/165500"><strong>Clinical Synopsis</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
|
|
<a href="/phenotypicSeries/PS165500"> <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="#clinicalFeatures">Clinical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#inheritance">Inheritance</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#pathogenesis">Pathogenesis</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#populationGenetics">Population Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#seeAlso"><strong>See Also</strong></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=(OPTIC ATROPHY) OR (OPA1)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=13690&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.diseaseinfosearch.org/x/8280" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://medlineplus.gov/genetics/condition/optic-atrophy-type-1" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=165500[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=98673" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Animal Models</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.alliancegenome.org/disease/DOID:0111441" 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/165500" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://omia.org/OMIA002871/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://wormbase.org/resources/disease/DOID:0111441" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 717336005<br />
|
|
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 98673<br />
|
|
|
|
|
|
<strong>DO:</strong> 0111441<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>
|
|
165500
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
OPTIC ATROPHY 1; OPA1
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
OPTIC ATROPHY, JUVENILE<br />
|
|
KJER-TYPE OPTIC ATROPHY<br />
|
|
OPTIC ATROPHY, KJER TYPE; OAK
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/3/975?start=-3&limit=10&highlight=975">
|
|
3q29
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Optic atrophy 1
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/165500"> 165500 </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">
|
|
OPA1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605290"> 605290 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/165500" 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/PS165500" 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/165500" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/165500" 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">
|
|
|
|
- Optic atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/76976005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">76976005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.2</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.20</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/377.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/377.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029124&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029124</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span><br /> -
|
|
Temporal optic nerve pallor <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2674707&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2674707</a>]</span><br /> -
|
|
Decreased visual acuity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/13164000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">13164000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234632&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234632</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007663" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007663</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007663" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007663</a>]</span><br /> -
|
|
Blue-yellow dyschromatopsia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/51886007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">51886007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85049009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85049009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H53.55" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H53.55</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/368.53" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">368.53</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0155017&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0155017</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000552" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000552</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000552" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000552</a>]</span><br /> -
|
|
Red-green dyschromatopsia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246674000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246674000</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/368.52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">368.52</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0155016&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0155016</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000642" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000642</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000642" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000642</a>]</span><br /> -
|
|
Centrocecal scotoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/33014001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">33014001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0271196&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0271196</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000576" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000576</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000576" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000576</a>]</span><br /> -
|
|
Central scotoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/38950008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">38950008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H53.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H53.41</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/368.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">368.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0152191&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0152191</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000603" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000603</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000603" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000603</a>]</span><br /> -
|
|
Pattern visual evoked potentials show reduced amplitude <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1833801&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1833801</a>]</span><br /> -
|
|
Strabismus (10%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22066006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22066006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H50.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H50.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H50.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H50.40</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038379&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038379</a>, <a href="https://bioportal.bioontology.org/search?q=C2020541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2020541</a>, <a href="https://bioportal.bioontology.org/search?q=C1423541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1423541</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000486</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000486</a>]</span><br /> -
|
|
Horizontal nystagmus (5%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/81756001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">81756001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0271385&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0271385</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000666" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000666</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000666" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000666</a>]</span><br /> -
|
|
Histology shows degeneration of retinal ganglion cells <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2674708&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2674708</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Phenotypic variability <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837514&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837514</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span><br /> -
|
|
Bimodal onset in early childhood (median 5 years) and young adulthood (21 to 30 years)<br /> -
|
|
Insidious onset <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/367326009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">367326009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1298634&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1298634</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003587" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003587</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003587" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003587</a>]</span><br /> -
|
|
Incomplete penetrance <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836598&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836598</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003829</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003829</a>]</span><br /> -
|
|
Prevalence ranges from 1 in 12,000 to 1 in 50,000<br /> -
|
|
See also optic atrophy with deafness (<a href="/entry/125250">125250</a>), an allelic disorder<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutation in the OPA1 mitochondrial dynamin-like GTPase gene (OPA1, <a href="/entry/605290#0001">605290.0001</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>
|
|
Optic atrophy
|
|
- <a href="/phenotypicSeries/PS165500">PS165500</a>
|
|
- 16 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/1/373?start=-3&limit=10&highlight=373"> 1p35.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/620629"> Optic atrophy 16 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/620629"> 620629 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608205"> MECR </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608205"> 608205 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/3/975?start=-3&limit=10&highlight=975"> 3q29 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/165500"> Optic atrophy 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/165500"> 165500 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605290"> OPA1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605290"> 605290 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/6/749?start=-3&limit=10&highlight=749"> 6q21 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616732"> Optic atrophy 10 with or without ataxia, impaired intellectual development and seizures </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616732"> 616732 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610502"> RTN4IP1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610502"> 610502 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/7/747?start=-3&limit=10&highlight=747"> 7q34 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/165510"> Optic atrophy 13 with retinal and foveal abnormalities </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/165510"> 165510 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600439"> SSBP1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600439"> 600439 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/8/338?start=-3&limit=10&highlight=338"> 8q21-q22 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/258500"> Optic atrophy 6 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="2 - The disorder was placed on the map by statistical methods"> 2 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/258500"> 258500 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/258500"> OPA6 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/258500"> 258500 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/10/118?start=-3&limit=10&highlight=118"> 10p12.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/617302"> ?Optic atrophy 11 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/617302"> 617302 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607472"> YME1L1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607472"> 607472 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/11/803?start=-3&limit=10&highlight=803"> 11q14.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612989"> Optic atrophy 7 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612989"> 612989 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612988"> TMEM126A </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612988"> 612988 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/12/279?start=-3&limit=10&highlight=279"> 12p11.21 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610708"> Optic atrophy 5 </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/610708"> 610708 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603850"> DNM1L </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603850"> 603850 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/16/480?start=-3&limit=10&highlight=480"> 16q21-q22 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616648"> Optic atrophy 8 </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="2 - The disorder was placed on the map by statistical methods"> 2 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616648"> 616648 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616648"> OPA8 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616648"> 616648 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/18/63?start=-3&limit=10&highlight=63"> 18p11.21 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618977"> Optic atrophy 12 </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/618977"> 618977 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604581"> AFG3L2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604581"> 604581 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/18/132?start=-3&limit=10&highlight=132"> 18q12.2-q12.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605293"> Optic atrophy 4 </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/605293"> 605293 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605293"> OPA4 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605293"> 605293 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/19/826?start=-3&limit=10&highlight=826"> 19q13.32 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/165300"> Optic atrophy 3 with cataract </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/165300"> 165300 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606580"> OPA3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606580"> 606580 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/22/300?start=-3&limit=10&highlight=300"> 22q13.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/620550"> Optic atrophy 14 </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/620550"> 620550 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615497"> MIEF1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615497"> 615497 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/22/323?start=-3&limit=10&highlight=323"> 22q13.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616289"> Optic atrophy 9 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616289"> 616289 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/100850"> ACO2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/100850"> 100850 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/22/357?start=-3&limit=10&highlight=357"> 22q13.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/620583"> Optic atrophy 15 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/620583"> 620583 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614479"> MCAT </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614479"> 614479 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/X/163?start=-3&limit=10&highlight=163"> Xp11.4-p11.21 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/311050"> Optic atrophy 2, X-linked </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="X-linked">XL</abbr>
|
|
|
|
</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/311050"> 311050 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/311050"> OPA2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/311050"> 311050 </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 optic atrophy-1 (OPA1) is caused by heterozygous mutation in the gene encoding the human homolog of the S. pombe dynamin-related protein Msp1 (OPA1; <a href="/entry/605290">605290</a>) on chromosome 3q29.</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>Autosomal dominant optic atrophy is characterized by an insidious onset of visual impairment in early childhood with moderate to severe loss of visual acuity, temporal optic disc pallor, color vision deficits, and centrocecal scotoma of variable density (<a href="#37" class="mim-tip-reference" title="Votruba, M., Fitzke, F. W., Holder, G. E., Carter, A., Bhattacharya, S. S., Moore, A. T. <strong>Clinical features in affected individuals from 21 pedigrees with dominant optic atrophy.</strong> Arch. Ophthal. 116: 351-358, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9514489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9514489</a>] [<a href="https://doi.org/10.1001/archopht.116.3.351" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9514489">Votruba et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9514489" 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>Some patients with mutations in the OPA1 gene may also develop extraocular neurologic features, such as deafness, progressive external ophthalmoplegia, muscle cramps, hyperreflexia, and ataxia; see <a href="/entry/125250">125250</a>. There appears to be a wide range of intermediate phenotypes (<a href="#42" class="mim-tip-reference" title="Yu-Wai-Man, P., Griffiths, P. G., Gorman, G. S., Lourenco, C. M., Wright, A. F., Auer-Grumbach, M., Toscano, A., Musumeci, O., Valentino, M. L., Caporali, L., Lamperti, C., Tallaksen, C. M., and 24 others. <strong>Multi-system neurological disease is common in patients with OPA1 mutations.</strong> Brain 133: 771-786, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20157015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20157015</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20157015[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/10.1093/brain/awq007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20157015">Yu-Wai-Man et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20157015" 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="#43" class="mim-tip-reference" title="Yu-Wai-Man, P., Griffiths, P. G., Hudson, G., Chinnery, P. F. <strong>Inherited mitochondrial optic neuropathies.</strong> J. Med. Genet. 46: 145-158, 2009. Note: Erratum: J. Med. Genet. 48: 284 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19001017/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19001017</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19001017[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmg.2007.054270" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19001017">Yu-Wai-Man et al. (2009)</a> provided a detailed review of autosomal dominant optic atrophy and Leber hereditary optic neuropathy (LHON; <a href="/entry/535000">535000</a>), with emphasis on the selective vulnerability of retinal ganglion cells to mitochondrial dysfunction in both disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19001017" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Genetic Heterogeneity of Optic Atrophy</em></strong></p><p>
|
|
Also see optic atrophy-2 (OPA2; <a href="/entry/311050">311050</a>), mapped to chromosome Xp11.4-p11.21; OPA3 (<a href="/entry/165300">165300</a>), caused by mutation in the OPA3 gene (<a href="/entry/606580">606580</a>) on chromosome 19q13; OPA4 (<a href="/entry/605293">605293</a>), mapped to chromosome 18q12.2-q12.3; OPA5 (<a href="/entry/610708">610708</a>), caused by mutation in the DNM1L gene (<a href="/entry/603850">603850</a>) on chromosome 12p11; OPA6 (<a href="/entry/258500">258500</a>), mapped to chromosome 8q21-q22; OPA7 (<a href="/entry/612989">612989</a>), caused by mutation in the TMEM126A gene (<a href="/entry/612988">612988</a>) on chromosome 11q14; OPA8 (<a href="/entry/616648">616648</a>), mapped to chromosome 16q21-q22; OPA9 (<a href="/entry/616289">616289</a>), caused by mutation in the ACO2 gene (<a href="/entry/100850">100850</a>) on chromosome 22q13; OPA10 (<a href="/entry/616732">616732</a>), caused by mutation in the RTN4IP1 gene (<a href="/entry/610502">610502</a>) on chromosome 6q21; OPA11 (<a href="/entry/617302">617302</a>), caused by mutation in the YME1L1 gene (<a href="/entry/607472">607472</a>) on chromosome 10p12; OPA12 (<a href="/entry/618977">618977</a>), caused by mutation in the AFG3L2 gene (<a href="/entry/604581">604581</a>) on chromosome 18p11; OPA13 (<a href="/entry/165510">165510</a>), caused by mutation in the SSBP1 gene (<a href="/entry/600439">600439</a>) on chromosome 7q34; OPA14 (<a href="/entry/620550">620550</a>), caused by mutation in the MIEF1 gene (<a href="/entry/615497">615497</a>) on chromosome 22q13; OPA15 (<a href="/entry/620583">620583</a>), caused by mutation in the MCAT gene (<a href="/entry/614479">614479</a>) on chromosome 22q13; and OPA16 (<a href="/entry/620629">620629</a>), caused by mutation in the MECR gene (<a href="/entry/608205">608205</a>) on chromosome 1p35.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="clinicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#19" class="mim-tip-reference" title="Iverson, H. A. <strong>Hereditary optic atrophy.</strong> AMA Arch. Ophthal. 59: 850-853, 1958.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13532092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13532092</a>] [<a href="https://doi.org/10.1001/archopht.1958.00940070064006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="13532092">Iverson (1958)</a> reported congenital optic atrophy in 3 generations. The clear autosomal dominant pattern of inheritance and congenital nature distinguished it from Leber hereditary optic atrophy (LHON; <a href="/entry/535000">535000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13532092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Caldwell, J. B. H., Howard, R. O., Riggs, L. A. <strong>Dominant juvenile optic atrophy. A study of two families and review of hereditary disease in childhood.</strong> Arch. Ophthal. 85: 133-147, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5545713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5545713</a>] [<a href="https://doi.org/10.1001/archopht.1971.00990050135004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5545713">Caldwell et al. (1971)</a> described 2 families with insidious onset of optic atrophy in childhood. There were no neurologic, congenital, or developmental abnormalities. <a href="#9" class="mim-tip-reference" title="Caldwell, J. B. H., Howard, R. O., Riggs, L. A. <strong>Dominant juvenile optic atrophy. A study of two families and review of hereditary disease in childhood.</strong> Arch. Ophthal. 85: 133-147, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5545713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5545713</a>] [<a href="https://doi.org/10.1001/archopht.1971.00990050135004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5545713">Caldwell et al. (1971)</a> classified the familial optic atrophies into 6 groups: congenital dominant, congenital recessive, juvenile dominant, juvenile recessive, Leber, and autosomal recessive Behr syndrome (<a href="/entry/210000">210000</a>). The features of the 6 groups were usefully compared. <a href="#35" class="mim-tip-reference" title="Snell, S. <strong>Diseases of the optic nerve. I. Hereditary or congenital optic atrophy and allied cases.</strong> Trans. Ophthal. Soc. U.K. 17: 66-81, 1897."None>Snell (1897)</a> is generally credited with first describing a form of optic atrophy separate from Leber optic atrophy. <a href="#36" class="mim-tip-reference" title="Stendahl-Brodin, L., Moller, E., Link, H. <strong>Hereditary optic atrophy with probable association with a specific HLA haplotype.</strong> J. Neurol. Sci. 38: 11-21, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/151734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">151734</a>] [<a href="https://doi.org/10.1016/0022-510x(78)90241-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="151734">Stendahl-Brodin et al. (1978)</a> described a family with probable autosomal dominant inheritance of late-onset optic atrophy. Linkage to HLA was suggested. <a href="#20" class="mim-tip-reference" title="Johnston, P. B., Gaster, R. N., Smith, V. C., Tripathi, R. C. <strong>A clinicopathologic study of autosomal dominant optic atrophy.</strong> Am. J. Ophthal. 88: 868-875, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/315716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">315716</a>] [<a href="https://doi.org/10.1016/0002-9394(79)90565-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="315716">Johnston et al. (1979)</a> studied an extensively affected kindred and had an opportunity for histologic examination of the eyes of an affected 56-year-old woman. Her vision had been severely reduced since childhood. Pathologic changes were diffuse atrophy of the ganglion cell layer of the retina and loss of myelin and nerve tissue within the optic nerve. They suggested that the disorder is a primary degeneration of retinal ganglion cells. Most affected members of the family had severe unclassified color defects. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5545713+315716+151734" 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="#15" class="mim-tip-reference" title="Eiberg, H., Kjer, B., Kjer, P., Rosenberg, T. <strong>Dominant optic atrophy (OPA1) mapped to chromosome 3q region. I. Linkage analysis.</strong> Hum. Molec. Genet. 3: 977-980, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951248</a>] [<a href="https://doi.org/10.1093/hmg/3.6.977" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7951248">Eiberg et al. (1994)</a> described autosomal dominant optic atrophy as being characterized by an insidious onset of optic atrophy in early childhood with moderate to severe decrease of visual acuity, blue-yellow dyschromatopsia, and centrocecal scotoma of varying density. Many affected members of the families may be unaware of having the disease or of its hereditary aspects. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951248" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#37" class="mim-tip-reference" title="Votruba, M., Fitzke, F. W., Holder, G. E., Carter, A., Bhattacharya, S. S., Moore, A. T. <strong>Clinical features in affected individuals from 21 pedigrees with dominant optic atrophy.</strong> Arch. Ophthal. 116: 351-358, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9514489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9514489</a>] [<a href="https://doi.org/10.1001/archopht.116.3.351" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9514489">Votruba et al. (1998)</a> evaluated the clinical features in 21 families with 3q-linked dominant optic atrophy. They found wide intra- and interfamilial phenotypic variation, with visual function deteriorating with age in only some families. There was evidence of degeneration of the ganglion cell layer, predominantly from central retina, but this was not the exclusive result of either parvocellular or magnocellular cell loss. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9514489" 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="Johnston, R. L., Seller, M. J., Behnam, J. T., Burdon, M. A., Spalton, D. J. <strong>Dominant optic atrophy: refining the clinical diagnostic criteria in light of genetic linkage studies.</strong> Ophthalmology 106: 123-128, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9917792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9917792</a>] [<a href="https://doi.org/10.1016/S0161-6420(99)90013-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9917792">Johnston et al. (1999)</a> refined the clinical diagnostic criteria for dominant optic atrophy on the basis of linkage studies, i.e., the study of subjects who had been classified clinically as definitely or possibly affected on the basis of a domiciliary examination before genetic analysis, and the comparison of these results with the haplotype analysis. Clinically, 43 subjects were identified as definitely affected, 4 as possibly affected, and 45 as unaffected. Visual acuity in affected subjects ranged from 6/6 to count fingers and declined with age. On genetic analysis, a specific haplotype was identified in each family, which was found in all definitely affected members but not in those regarded as unaffected. The 4 possibly affected individuals also bore the haplotype that segregated with the disorder. Contrary to accepted criteria, symptoms began before the age of 10 years in only 58% of affected individuals. Visual acuity in affected subjects was highly variable. A mild degree of temporal or diffuse pallor of the optic disc and minimal color vision defects, in the context of the family with dominant optic atrophy, were highly suggestive of an individual being affected, even if visual acuity was normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9917792" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 large U.S. midwestern families with autosomal dominant optic atrophy, <a href="#10" class="mim-tip-reference" title="Chen, A. S., Kovach, M. J., Herman, K., Avakian, A., Frank, W., Forrester, S., Lin, J.-P., Kimonis, V. <strong>Clinical heterogeneity in autosomal dominant optic atrophy in two 3q28-qter linked central Illinois families.</strong> Genet. Med. 2: 283-289, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11399209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11399209</a>] [<a href="https://doi.org/10.1097/00125817-200009000-00003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11399209">Chen et al. (2000)</a> showed linkage to 3q28-q29 and pointed out considerable intrafamilial phenotypic variation as well as sex-influenced severity. Visual loss among affected males was more severe than among affected females. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11399209" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Fournier, A. V., Damji, K. F., Epstein, D. L., Pollock, S. C. <strong>Disc excavation in dominant optic atrophy.</strong> Ophthalmology 108: 1595-1602, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11535456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11535456</a>] [<a href="https://doi.org/10.1016/s0161-6420(01)00696-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11535456">Fournier et al. (2001)</a> examined optic disc morphology in patients with dominant optic atrophy to elucidate features that would distinguish dominant optic atrophy from normal tension glaucoma (<a href="/entry/606657">606657</a>). The optic atrophy patients had a mild to moderate reduction in visual acuity and color vision. Seventy-eight percent had a temporal wedge-shaped area of optic disc excavation. All involved eyes had moderate to severe pallor of the temporal neuroretinal rim, with milder pallor of the remaining noncupped rim. All eyes had a slate-gray crescent within the neuroretinal rim tissue and some degree of peripapillary atrophy. The authors concluded that several clinical features, including early age of onset, preferential loss of central vision, sparing of the peripheral fields, pallor of the remaining neuroretinal rim, and a family history of unexplained visual loss or optic atrophy, help distinguish patients with dominant optic atrophy from those with normal tension glaucoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11535456" 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 analyze the influence of OPA1 gene mutations on optic nerve head morphology in patients with dominant optic atrophy, <a href="#4" class="mim-tip-reference" title="Barboni, P., Carbonelli, M., Savini, G., Foscarini. B., Parisi, V., Valentino, M. L., Carta, A., De Negri, A., Sadun, F., Zeviani, M., Sadun, A. A., Schimpf, S., Wissinger, B., Carelli, V. <strong>OPA1 mutations associated with dominant optic atrophy influence optic nerve head size.</strong> Ophthalmology 117: 1547-1553, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20417568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20417568</a>] [<a href="https://doi.org/10.1016/j.ophtha.2009.12.042" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20417568">Barboni et al. (2010)</a> studied the optic nerve head of 28 OPA1 mutation-positive patients from 11 pedigrees and 56 age-matched controls by optical coherence tomography (OCT). Patients showed a significantly smaller optic disc area (P less than 0.0001), and vertical (P = 0.018), and horizontal (P less than 0.0001) disc diameters, compared with controls. Stratification of the results for the single OPA1 mutation revealed normal optic nerve head area with 2 mutations, whereas a missense mutation linked to a 'dominant optic atrophy plus' phenotype (<a href="/entry/605290#0017">605290.0017</a>) had the smallest ONH measurements. <a href="#4" class="mim-tip-reference" title="Barboni, P., Carbonelli, M., Savini, G., Foscarini. B., Parisi, V., Valentino, M. L., Carta, A., De Negri, A., Sadun, F., Zeviani, M., Sadun, A. A., Schimpf, S., Wissinger, B., Carelli, V. <strong>OPA1 mutations associated with dominant optic atrophy influence optic nerve head size.</strong> Ophthalmology 117: 1547-1553, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20417568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20417568</a>] [<a href="https://doi.org/10.1016/j.ophtha.2009.12.042" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20417568">Barboni et al. (2010)</a> concluded that their observations suggested a theretofore unrecognized role for OPA1 in eye development, and in particular in modeling optic nerve head size and conformation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20417568" 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 optical coherence tomography (OCT), <a href="#5" class="mim-tip-reference" title="Barboni, P., Savini, G., Parisi, V., Carbonelli, M., La Morgia, C., Maresca, A., Sadun, F., De Negri, A. M., Carta, A., Sadun, A. A., Carelli, V. <strong>Retinal nerve fiber layer thickness in dominant optic atrophy.</strong> Ophthalmology 118: 2076-2080, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21621262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21621262</a>] [<a href="https://doi.org/10.1016/j.ophtha.2011.02.027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21621262">Barboni et al. (2011)</a> compared the retinal nerve fiber layers (RNFLs) of 33 dominant optic atrophy patients with those of 43 healthy control subjects matched for age and optic nerve head size. They found that patients had significant RNFL thickness reduction in all quadrants, with a preferential involvement of the temporal and inferior sectors. The progressive decline in RNFL thickness with age was similar to that observed in healthy subjects and was more evident in the 2 quadrants with higher residual amounts of fibers, i.e., the superior and inferior quadrants. The temporal quadrant was profoundly depleted of fiber so that the further rate of loss of microns per year was close to zero, whereas the nasal quadrant was spared the most by neurodegeneration. <a href="#5" class="mim-tip-reference" title="Barboni, P., Savini, G., Parisi, V., Carbonelli, M., La Morgia, C., Maresca, A., Sadun, F., De Negri, A. M., Carta, A., Sadun, A. A., Carelli, V. <strong>Retinal nerve fiber layer thickness in dominant optic atrophy.</strong> Ophthalmology 118: 2076-2080, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21621262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21621262</a>] [<a href="https://doi.org/10.1016/j.ophtha.2011.02.027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21621262">Barboni et al. (2011)</a> concluded that these findings, together with their description of small optic nerve head size in dominant optic atrophy (<a href="#4" class="mim-tip-reference" title="Barboni, P., Carbonelli, M., Savini, G., Foscarini. B., Parisi, V., Valentino, M. L., Carta, A., De Negri, A., Sadun, F., Zeviani, M., Sadun, A. A., Schimpf, S., Wissinger, B., Carelli, V. <strong>OPA1 mutations associated with dominant optic atrophy influence optic nerve head size.</strong> Ophthalmology 117: 1547-1553, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20417568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20417568</a>] [<a href="https://doi.org/10.1016/j.ophtha.2009.12.042" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20417568">Barboni et al., 2010</a>), strongly suggested that patients with this disease are born with fewer optic nerve axons and supported the hypothesis that subsequent visual loss depends on further age-related loss of fibers, which also occurred in controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21621262+20417568" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="inheritance" class="mim-anchor"></a>
|
|
<h4 href="#mimInheritanceFold" id="mimInheritanceToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimInheritanceToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimInheritanceFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>The transmission pattern of OPA1 in the families reported by <a href="#12" class="mim-tip-reference" title="Cohn, A. C., Toomes, C., Potter, C., Towns, K. V., Hewitt, A. W., Inglehearn, C. F., Craig, J. E., Mackey, D. A. <strong>Autosomal dominant optic atrophy: penetrance and expressivity in patients with OPA1 mutations.</strong> Am. J. Ophthal. 143: 656-662, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17306754/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17306754</a>] [<a href="https://doi.org/10.1016/j.ajo.2006.12.038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17306754">Cohn et al. (2007)</a> was consistent with autosomal dominant inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17306754" 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="pathogenesis" class="mim-anchor"></a>
|
|
<h4 href="#mimPathogenesisFold" id="mimPathogenesisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimPathogenesisToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Pathogenesis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimPathogenesisFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>The pathogenic characteristics of OPA1 resemble those of Leber hereditary optic neuropathy (<a href="/entry/535000">535000</a>), which results from a defect of the mitochondrion. Mutations in the mitochondrial gene responsible presumably lead to insufficient energy supply in the highly energy-demanding neurons of the optic nerve, notably the papillomacular bundle, and cause blindness by a compromise of axonal transport in retinal ganglion cells. <a href="#1" class="mim-tip-reference" title="Alexander, C., Votruba, M., Pesch, U. E. A., Thiselton, D. L., Mayer, S., Moore, A., Rodriguez, M., Kellner, U., Leo-Kottler, B., Auburger, G., Bhattacharya, S. S., Wissinger, B. <strong>OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28.</strong> Nature Genet. 26: 211-215, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11017080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11017080</a>] [<a href="https://doi.org/10.1038/79944" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11017080">Alexander et al. (2000)</a> hypothesized that mutations in the OPA1 gene affect mitochondrial integrity, resulting in an impairment of energy supply. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11017080" 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 phosphorus magnetic resonance spectroscopy, <a href="#26" class="mim-tip-reference" title="Lodi, R., Tonon, C., Valentino, M. L., Iotti, S., Clementi, V., Malucelli, E., Barboni, P., Longanesi, L., Schimpf, S., Wissinger, B., Baruzzi, A., Barbiroli, B., Carelli, V. <strong>Deficit of in vivo mitochondrial ATP production in OPA1-related dominant optic atrophy.</strong> Ann. Neurol. 56: 719-723, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15505825/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15505825</a>] [<a href="https://doi.org/10.1002/ana.20278" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15505825">Lodi et al. (2004)</a> demonstrated defective oxidative phosphorylation in 6 OPA1 patients from 2 unrelated families with a 4-bp deletion in the OPA1 gene (<a href="/entry/605290#0003">605290.0003</a>). The time constant of postexercise phosphocreatine resynthesis was significantly increased in patients compared to controls, indicating a reduced rate of mitochondrial ATP production in the patients. <a href="#26" class="mim-tip-reference" title="Lodi, R., Tonon, C., Valentino, M. L., Iotti, S., Clementi, V., Malucelli, E., Barboni, P., Longanesi, L., Schimpf, S., Wissinger, B., Baruzzi, A., Barbiroli, B., Carelli, V. <strong>Deficit of in vivo mitochondrial ATP production in OPA1-related dominant optic atrophy.</strong> Ann. Neurol. 56: 719-723, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15505825/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15505825</a>] [<a href="https://doi.org/10.1002/ana.20278" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15505825">Lodi et al. (2004)</a> noted that similar findings had been observed in patients with LHON. <a href="#27" class="mim-tip-reference" title="Lodi, R., Tonon, C., Valentino, M. L., Manners, D., Testa, C., Malucelli, E., La Morgia, C., Barboni, P., Carbonelli, M., Schimpf, S., Wissinger, B., Zeviani, M., Baruzzi, A., Liguori, R., Barbiroli, B., Carelli, V. <strong>Defective mitochondrial adenosine triphosphate production in skeletal muscle from patients with dominant optic atrophy due to OPA1 mutations.</strong> Arch. Neurol. 68: 67-73, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20837821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20837821</a>] [<a href="https://doi.org/10.1001/archneurol.2010.228" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20837821">Lodi et al. (2011)</a> performed similar studies as <a href="#26" class="mim-tip-reference" title="Lodi, R., Tonon, C., Valentino, M. L., Iotti, S., Clementi, V., Malucelli, E., Barboni, P., Longanesi, L., Schimpf, S., Wissinger, B., Baruzzi, A., Barbiroli, B., Carelli, V. <strong>Deficit of in vivo mitochondrial ATP production in OPA1-related dominant optic atrophy.</strong> Ann. Neurol. 56: 719-723, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15505825/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15505825</a>] [<a href="https://doi.org/10.1002/ana.20278" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15505825">Lodi et al. (2004)</a> 18 patients, including 6 previously reported by <a href="#26" class="mim-tip-reference" title="Lodi, R., Tonon, C., Valentino, M. L., Iotti, S., Clementi, V., Malucelli, E., Barboni, P., Longanesi, L., Schimpf, S., Wissinger, B., Baruzzi, A., Barbiroli, B., Carelli, V. <strong>Deficit of in vivo mitochondrial ATP production in OPA1-related dominant optic atrophy.</strong> Ann. Neurol. 56: 719-723, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15505825/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15505825</a>] [<a href="https://doi.org/10.1002/ana.20278" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15505825">Lodi et al. (2004)</a>, with genetically confirmed OPA1 due to different mutations. Sixteen patients carried truncating mutations resulting in haploinsufficiency, and 2 patients had missense mutations. Calf muscles from patients showed reduced phosphorylation potential in patients at rest, indicating reduced energy reserve, although only 4 patients had levels below the normal range. Patients showed shorter exercise duration compared to controls, indicating reduced oxidative capacity. Postexercise skeletal muscle Vmax of mitochondrial ATP synthesis was reduced by 36% in patients compared to controls, and only 2 patients had normal Vmax levels. Four of 10 patients had increased serum lactate after exercise. Despite these defects, muscle biopsies available from 5 patients did not show clear-cut hallmarks of mitochondrial myopathy, such as ragged-red fibers, and there was not clear evidence of mtDNA deletions. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15505825+20837821" 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="#29" class="mim-tip-reference" title="Payne, M., Yang, Z., Katz, B. J., Warner, J. E. A., Weight, C. J., Zhao, Y., Pearson, E. D., Treft, R. L., Hillman, T., Kennedy, R. J., Meire, F. M., Zhang, K. <strong>Dominant optic atrophy, sensorineural hearing loss, ptosis, and ophthalmoplegia: a syndrome caused by a missense mutation in OPA1.</strong> Am. J. Ophthal. 138: 749-755, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15531309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15531309</a>] [<a href="https://doi.org/10.1016/j.ajo.2004.06.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15531309">Payne et al. (2004)</a> hypothesized that although OPA1 is a nuclear gene, the fact that the gene product localizes to mitochondria suggests that mitochondrial dysfunction might be the final common pathway for many forms of syndromic and nonsyndromic optic atrophy, hearing loss, and external ophthalmoplegia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15531309" 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 quantitative real-time PCR, <a href="#23" class="mim-tip-reference" title="Kim, J. Y., Hwang, J.-M., Ko, H. S., Seong, M.-W., Park, B.-J., Park, S. S. <strong>Mitochondrial DNA content is decreased in autosomal dominant optic atrophy.</strong> Neurology 64: 966-972, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15781809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15781809</a>] [<a href="https://doi.org/10.1212/01.WNL.0000157282.76715.B1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15781809">Kim et al. (2005)</a> found significantly decreased levels of cellular mtDNA in blood from 4 of 8 patients with OPA1 (range, 412.0 to 648.0 copies per cell) compared to controls (1,148.6 +/- 406.9). Three patients had decreased levels (813.2 to 1,133.6), and 1 patient had normal levels (1,455.3). The findings were consistent with the hypothesis that OPA1 gene mutations result in decreased numbers of mitochondrial organelles via apoptosis. However, neither mtDNA content nor genotype correlated with phenotype, indicating that additional epigenetic factors are involved. <a href="#23" class="mim-tip-reference" title="Kim, J. Y., Hwang, J.-M., Ko, H. S., Seong, M.-W., Park, B.-J., Park, S. S. <strong>Mitochondrial DNA content is decreased in autosomal dominant optic atrophy.</strong> Neurology 64: 966-972, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15781809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15781809</a>] [<a href="https://doi.org/10.1212/01.WNL.0000157282.76715.B1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15781809">Kim et al. (2005)</a> postulated that selective damage to retinal ganglion cells in OPA1 may result from a combination of high energy requirements of retinal cells in the macular area and increased sensitivity of retinal ganglial cells to free radicals and oxidative stress. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15781809" 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="Amati-Bonneau, P., Guichet, A., Olichon, A., Chevrollier, A., Viala, F., Miot, S., Ayuso, C., Odent, S., Arrouet, C., Verny, C., Calmels, M.-N., Simard, G., Belenguer, P., Wang, J., Puel, J.-L., Hamel, C., Malthiery, Y., Bonneau, D., Lenaers, G., Reynier, P. <strong>OPA1 R445H mutation in optic atrophy associated with sensorineural deafness.</strong> Ann. Neurol. 58: 958-963, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16240368/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16240368</a>] [<a href="https://doi.org/10.1002/ana.20681" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16240368">Amati-Bonneau et al. (2005)</a> found fragmentation of the mitochondrial network and defects in oxidative phosphorylation in skin fibroblasts from patients with optic atrophy and deafness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16240368" 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 fibroblasts derived from 16 patients with hereditary optic neuropathy, including either LHON, OPA1, or OPA3, <a href="#11" class="mim-tip-reference" title="Chevrollier, A., Guillet, V., Loiseau, D., Gueguen, N., de Crescenzo, M.-A. P., Verny, C., Ferre, M., Dollfus, H., Odent, S., Milea, D., Goizet, C., Amati-Bonneau, P., Procaccio, V., Bonneau, D., Reynier, P. <strong>Hereditary optic neuropathies share a common mitochondrial coupling defect.</strong> Ann. Neurol. 63: 794-798, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18496845/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18496845</a>] [<a href="https://doi.org/10.1002/ana.21385" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18496845">Chevrollier et al. (2008)</a> found a common coupling defect of oxidative phosphorylation, resulting in reduced efficiency of ATP synthesis. LHON fibroblasts showed a mean decrease of 39% in complex I activity compared to controls. OPA1 and OPA3 fibroblasts showed normal complex I activities, but a mean decrease of 25% in complex IV activity and a mean 60% increase in complex V activity. Resting respiration was about twice as high in all LHON, OPA1, and OPA3 fibroblasts compared to controls, reflecting a proton leak or electron slip. However, all mutant cell lines used a greater proportion of routine respiratory capacity during routine compared to controls, suggesting a compensatory mechanism. The energy defect was most pronounced in fibroblasts from patients with additional neurologic symptoms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18496845" 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="#44" class="mim-tip-reference" title="Yu-Wai-Man, P., Sitarz, K. S., Samuels, D. C., Griffiths, P. G., Reeve, A. K., Bindoff, L. A., Horvath, R., Chinnery, P. F. <strong>OPA1 mutations cause cytochrome c oxidase deficiency due to loss of wild-type mtDNA molecules.</strong> Hum. Molec. Genet. 19: 3043-3052, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20484224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20484224</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20484224[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/10.1093/hmg/ddq209" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20484224">Yu-Wai-Man et al. (2010)</a> investigated the mtDNA changes induced by OPA1 mutations in skeletal muscle biopsies from 15 patients with both isolated DOA and neuromuscularly impaired (DOA+; <a href="/entry/125250">125250</a>) phenotypes. There was a 2- to 4-fold increase in mtDNA copy number at the single-fiber level, and patients with DOA+ features had significantly greater mtDNA proliferation in their cytochrome c oxidase (COX; see <a href="/entry/516030">516030</a>)-negative skeletal muscle fibers compared to patients with isolated optic neuropathy. Low levels of wildtype mtDNA molecules were present in COX-deficient muscle fibers from both isolated DOA and DOA+ patients, implicating haploinsufficiency as the mechanism responsible for the biochemical defect. The authors proposed a 'maintenance of wildtype' hypothesis, with secondary mtDNA deletions induced by OPA1 mutations triggering a compensatory mitochondrial proliferative response in order to maintain an optimal level of wildtype mtDNA genomes. However, when deletion levels reach a critical level, further mitochondrial proliferation may lead to replication of the mutant species at the expense of wildtype mtDNA, resulting in the loss of respiratory chain COX activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20484224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Ban, T., Heymann, J. A. W., Song, Z., Hinshaw, J. E., Chan, D. C. <strong>OPA1 disease alleles causing dominant optic atrophy have defects in cardiolipin-stimulated GTP hydrolysis and membrane tubulation.</strong> Hum. Molec. Genet. 19: 2113-2122, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20185555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20185555</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20185555[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/10.1093/hmg/ddq088" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20185555">Ban et al. (2010)</a> showed that OPA1 has a low basal rate of GTP hydrolysis that is dramatically enhanced by association with liposomes containing negative phospholipids, such as cardiolipin. Lipid association triggered assembly of OPA1 into higher order oligomers. In addition, OPA1 could promote the protrusion of lipid tubules from the surface of cardiolipin-containing liposomes. In such lipid protrusions, OPA1 assemblies were observed on the outside of the lipid tubule surface, a protein-membrane topology similar to that of classical dynamins. The membrane tubulation activity of OPA1 was suppressed by GTP-gamma-S. OPA1 disease alleles associated with dominant optic atrophy displayed selective defects in several activities, including cardiolipin association, GTP hydrolysis, and membrane tubulation. <a href="#3" class="mim-tip-reference" title="Ban, T., Heymann, J. A. W., Song, Z., Hinshaw, J. E., Chan, D. C. <strong>OPA1 disease alleles causing dominant optic atrophy have defects in cardiolipin-stimulated GTP hydrolysis and membrane tubulation.</strong> Hum. Molec. Genet. 19: 2113-2122, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20185555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20185555</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20185555[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/10.1093/hmg/ddq088" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20185555">Ban et al. (2010)</a> concluded that interaction of OPA1 with membranes can stimulate higher order assembly, enhance GTP hydrolysis, and lead to membrane deformation into tubules. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20185555" 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="populationGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimPopulationGeneticsFold" id="mimPopulationGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimPopulationGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimPopulationGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>In a population-based epidemiologic study of autosomal dominant optic atrophy in the north of England, <a href="#41" class="mim-tip-reference" title="Yu-Wai-Man, P., Griffiths, P. G., Burke, A., Sellar, P. W., Clarke, M. P., Gnanaraj, L., Ah-Kine, D., Hudson, G., Czermin, B., Taylor, R. W., Horvath, R., Chinnery, P. F. <strong>The prevalence and natural history of dominant optic atrophy due to OPA1 mutations.</strong> Ophthalmology 117: 1538-1546, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20417570/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20417570</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20417570[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ophtha.2009.12.038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20417570">Yu-Wai-Man et al. (2010)</a> determined that the minimum point prevalence was 2.87 per 100,000, or approximately 1 in 35,000. The point prevalence was 2.09 per 100,000 when only OPA1-positive cases were considered. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20417570" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>By linkage studies in 3 extended Danish pedigrees using highly informative short tandem repeat polymorphisms, <a href="#15" class="mim-tip-reference" title="Eiberg, H., Kjer, B., Kjer, P., Rosenberg, T. <strong>Dominant optic atrophy (OPA1) mapped to chromosome 3q region. I. Linkage analysis.</strong> Hum. Molec. Genet. 3: 977-980, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951248</a>] [<a href="https://doi.org/10.1093/hmg/3.6.977" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7951248">Eiberg et al. (1994)</a> found linkage of the disease gene, which they symbolized OPA1, to a (CA)n dinucleotide repeat polymorphism at locus D3S1314; maximum lod = 10.34 at theta = 0.075. Using 2 additional chromosome 3 markers, they mapped the OPA1 gene in the region between D3S1314 and D3S1265: 3q28-qter. <a href="#28" class="mim-tip-reference" title="Lunkes, A., Hartung, U., Magarino, C., Rodriguez, M., Palmero, A., Rodriguez, L., Heredero, L., Weissenbach, J., Weber, J., Auburger, G. <strong>Refinement of the OPA1 gene locus on chromosome 3q28-q29 to a region of 2-8 cM, in one Cuban pedigree with autosomal dominant optic atrophy type Kjer. (Letter)</strong> Am. J. Hum. Genet. 57: 968-970, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7573062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7573062</a>]" pmid="7573062">Lunkes et al. (1995)</a> refined the localization of the OPA1 gene on 3q28-q29 to a region of 2-8 cM by studies in a Cuban pedigree with autosomal dominant optic atrophy of the KJER type. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7951248+7573062" 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="Bonneau, D., Souied, E., Gerber, S., Rozet, J.-M., D'Haens, E., Journel, H., Plessis, G., Weissenbach, J., Munnich, A., Kaplan, J. <strong>No evidence of genetic heterogeneity in dominant optic atrophy.</strong> J. Med. Genet. 32: 951-953, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8825922/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8825922</a>] [<a href="https://doi.org/10.1136/jmg.32.12.951" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8825922">Bonneau et al. (1995)</a> confirmed the mapping of optic atrophy-1 to 3q28-qter, showing close linkage of the disease locus to 3 newly reported microsatellite DNA markers in 4 French families. There was no evidence of genetic heterogeneity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8825922" 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 5 British pedigrees, <a href="#38" class="mim-tip-reference" title="Votruba, M., Moore, A. T., Bhattacharya, S. S. <strong>Genetic refinement of dominant optic atrophy (OPA1) locus to within a 2 cM interval of chromosome 3q.</strong> J. Med. Genet. 34: 117-121, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9039986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9039986</a>] [<a href="https://doi.org/10.1136/jmg.34.2.117" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9039986">Votruba et al. (1997)</a> confirmed linkage to 3q28-q29 and narrowed the assignment to a 2-cM segment. In a large family in which <a href="#8" class="mim-tip-reference" title="Brown, J., Jr., Fingert, J. H., Taylor, C. M., Lake, M., Sheffield, V. C., Stone, E. M. <strong>Clinical and genetic analysis of a family affected with dominant optic atrophy (OPA1).</strong> Arch. Ophthal. 115: 95-99, 1997. Note: Erratum: Arch. Ophthal. 115: 663 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9006432/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9006432</a>] [<a href="https://doi.org/10.1001/archopht.1997.01100150097016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9006432">Brown et al. (1997)</a> found 34 affected members, linkage analysis revealed significant lod scores with 9 markers on 3q. The highest lod score, 10.1, was obtained with marker D3S2305. Analysis of recombinants narrowed the disease interval to approximately 3.8 cM, flanked by D3S3669 (centromeric) and D3S1305 (telomeric). Most affected members experienced loss of vision in the first decade of life and most progressed to 20/800 or poorer visual acuity by age 60, although 2 patients maintained visual acuities of 20/40 at that age. Similarly, by linkage analysis in a British family with 16 affected members, <a href="#21" class="mim-tip-reference" title="Johnston, R. L., Burdon, M. A., Spalton, D. J., Bryant, S. P., Behnam, J. T., Seller, M. J. <strong>Dominant optic atrophy, Kjer type: linkage analysis and clinical features in a large British pedigree.</strong> Arch. Ophthal. 115: 100-103, 1997. Note: Erratum: Arch. Ophthal. 115: 681 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9006433/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9006433</a>] [<a href="https://doi.org/10.1001/archopht.1997.01100150102017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9006433">Johnston et al. (1997)</a> mapped the OPA1 gene to the 3q27-q28 region. <a href="#39" class="mim-tip-reference" title="Votruba, M., Moore, A. T., Bhattacharya, S. S. <strong>Demonstration of a founder effect and fine mapping of dominant optic atrophy locus on 3q28-qter by linkage disequilibrium method: a study of 38 British Isles pedigrees.</strong> Hum. Genet. 102: 79-86, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9490303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9490303</a>] [<a href="https://doi.org/10.1007/s004390050657" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9490303">Votruba et al. (1998)</a> further narrowed the optic atrophy-1 linkage interval on chromosome 3q28 to within 400 kb of the marker D3S1523, with a multipoint analysis maximum lod score of 8.01. They studied a total of 38 families with dominant optic atrophy, unrelated on the basis of genealogy, from a database of genetic eye disease families originating from the British isles. Allelic frequency analysis and haplotype parsimony analysis showed evidence of founder effect in 36 of the 38 pedigrees. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9039986+9490303+9006432+9006433" 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>Heterogeneity</em></strong></p><p>
|
|
Heterogeneity within the group of autosomal dominant optic atrophy was suggested by linkage studies (<a href="#24" class="mim-tip-reference" title="Kivlin, J. D., Lovrien, E. W., Bishop, D. T., Maumenee, I. H. <strong>Linkage analysis in dominant optic atrophy.</strong> Am. J. Hum. Genet. 35: 1190-1195, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6580816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6580816</a>]" pmid="6580816">Kivlin et al., 1983</a>; <a href="#32" class="mim-tip-reference" title="Seller, M. J., Behnam, J. T., Lewis, C. M., Johnston, R. L., Burdon, M. A., Spalton, D. J. <strong>Linkage studies in dominant optic atrophy, Kjer type: possible evidence for heterogeneity.</strong> J. Med. Genet. 34: 967-972, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9429135/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9429135</a>] [<a href="https://doi.org/10.1136/jmg.34.12.967" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9429135">Seller et al., 1997</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9429135+6580816" 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="#1" class="mim-tip-reference" title="Alexander, C., Votruba, M., Pesch, U. E. A., Thiselton, D. L., Mayer, S., Moore, A., Rodriguez, M., Kellner, U., Leo-Kottler, B., Auburger, G., Bhattacharya, S. S., Wissinger, B. <strong>OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28.</strong> Nature Genet. 26: 211-215, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11017080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11017080</a>] [<a href="https://doi.org/10.1038/79944" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11017080">Alexander et al. (2000)</a> and <a href="#14" class="mim-tip-reference" title="Delettre, C., Lenaers, G., Griffoin, J.-M., Gigarel, N., Lorenzo, C., Belenguer, P., Pelloquin, L., Grosgeorge, J., Turc-Carel, C., Perret, E., Astarie-Dequeker, C., Lasquellec, L., Arnaud, B., Ducommun, B., Kaplan, J., Hamel, C. P. <strong>Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy.</strong> Nature Genet. 26: 207-210, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11017079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11017079</a>] [<a href="https://doi.org/10.1038/79936" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11017079">Delettre et al. (2000)</a> independently identified a gene (OPA1; <a href="/entry/605290">605290</a>) in the optic atrophy-1 candidate region that encodes a polypeptide with homology to dynamin-related GTPases. In patients with optic atrophy, both <a href="#1" class="mim-tip-reference" title="Alexander, C., Votruba, M., Pesch, U. E. A., Thiselton, D. L., Mayer, S., Moore, A., Rodriguez, M., Kellner, U., Leo-Kottler, B., Auburger, G., Bhattacharya, S. S., Wissinger, B. <strong>OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28.</strong> Nature Genet. 26: 211-215, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11017080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11017080</a>] [<a href="https://doi.org/10.1038/79944" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11017080">Alexander et al. (2000)</a> and <a href="#14" class="mim-tip-reference" title="Delettre, C., Lenaers, G., Griffoin, J.-M., Gigarel, N., Lorenzo, C., Belenguer, P., Pelloquin, L., Grosgeorge, J., Turc-Carel, C., Perret, E., Astarie-Dequeker, C., Lasquellec, L., Arnaud, B., Ducommun, B., Kaplan, J., Hamel, C. P. <strong>Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy.</strong> Nature Genet. 26: 207-210, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11017079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11017079</a>] [<a href="https://doi.org/10.1038/79936" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11017079">Delettre et al. (2000)</a> identified mutations in the OPA1 gene (<a href="/entry/605290#0001">605290.0001</a>-<a href="/entry/605290#0009">605290.0009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11017080+11017079" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Cohn, A. C., Toomes, C., Potter, C., Towns, K. V., Hewitt, A. W., Inglehearn, C. F., Craig, J. E., Mackey, D. A. <strong>Autosomal dominant optic atrophy: penetrance and expressivity in patients with OPA1 mutations.</strong> Am. J. Ophthal. 143: 656-662, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17306754/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17306754</a>] [<a href="https://doi.org/10.1016/j.ajo.2006.12.038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17306754">Cohn et al. (2007)</a> identified OPA1 mutations in 11 of 17 Australian pedigrees with autosomal dominant optic atrophy. The penetrance in the families with complete sib recruitment was 82.5%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17306754" 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 multiplex ligation probe amplification (MLPA), <a href="#18" class="mim-tip-reference" title="Fuhrmann, N., Alavi, M. V., Bitoun, P., Woernle, S., Auburger, G., Leo-Kottler, B., Yu-Wai-Man, P., Chinnery, P., Wissinger, B. <strong>Genomic rearrangements in OPA1 are frequent in patients with autosomal dominant optic atrophy.</strong> J. Med. Genet. 46: 136-144, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19181907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19181907</a>] [<a href="https://doi.org/10.1136/jmg.2008.062570" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19181907">Fuhrmann et al. (2009)</a> identified heterozygous deletions of 1 or more exons in the OPA1 gene in 5 of 42 OPA1 probands who did not have point mutations by previous screening techniques. Three additional probands had a heterozygous in-frame duplication of exons 7 to 9. Overall, the results were consistent with haploinsufficiency as the disease mechanism rather than gain of function. <a href="#18" class="mim-tip-reference" title="Fuhrmann, N., Alavi, M. V., Bitoun, P., Woernle, S., Auburger, G., Leo-Kottler, B., Yu-Wai-Man, P., Chinnery, P., Wissinger, B. <strong>Genomic rearrangements in OPA1 are frequent in patients with autosomal dominant optic atrophy.</strong> J. Med. Genet. 46: 136-144, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19181907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19181907</a>] [<a href="https://doi.org/10.1136/jmg.2008.062570" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19181907">Fuhrmann et al. (2009)</a> estimated that OPA1 genomic rearrangements have a prevalence of 12.9% in patients with autosomal dominant optic atrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19181907" 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 define the prevalence and natural history of autosomal dominant optic atrophy, <a href="#41" class="mim-tip-reference" title="Yu-Wai-Man, P., Griffiths, P. G., Burke, A., Sellar, P. W., Clarke, M. P., Gnanaraj, L., Ah-Kine, D., Hudson, G., Czermin, B., Taylor, R. W., Horvath, R., Chinnery, P. F. <strong>The prevalence and natural history of dominant optic atrophy due to OPA1 mutations.</strong> Ophthalmology 117: 1538-1546, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20417570/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20417570</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20417570[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ophtha.2009.12.038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20417570">Yu-Wai-Man et al. (2010)</a> performed a population-based epidemiologic and molecular study of 76 probands with a clinical diagnosis of autosomal dominant optic atrophy from the north of England. They detected OPA1 mutations in 57.6% of probands with a positive family history of optic atrophy (19/33) and in 14.0% of singleton cases (6/43). Approximately 2/3 of families with dominant optic atrophy harbored OPA1 mutations (14/22, 63%), and 5 novel OPA1 mutations were identified. Only 1 family carried a large-scale OPA1 rearrangement, and no OPA3 mutations were found in their optic atrophy cohort. OPA1 missense mutations were associated with a significantly worse visual outcome compared with other mutational subtypes (P = 0.0001). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20417570" 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>Exclusion Studies</em></strong></p><p>
|
|
<a href="#40" class="mim-tip-reference" title="Votruba, M., Payne, A., Moore, A. T., Bhattacharya, S. S. <strong>Dominant optic atrophy: exclusion and fine genetic mapping of the candidate gene, HRY.</strong> Mammalian Genome 9: 784-787, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9745030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9745030</a>] [<a href="https://doi.org/10.1007/s003359900867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9745030">Votruba et al. (1998)</a> excluded the candidate gene HRY (<a href="/entry/139605">139605</a>) as the causative gene for OPA on chromosome 3q. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9745030" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>'Belly spot and tail' (Bst) is a semidominant, homozygous lethal mutation in mouse that arose in the inbred strain C57BLKS (C57BL/Ks). Heterozygous mice have a kinky tail, white feet, and a white spot at the ventral midline. The phenotype arises from a deletion within the RPL24 (<a href="/entry/604180">604180</a>) riboprotein gene. In approximately 50% of the heterozygous mice, there is a reduction or a complete absence of the pupillary light reflex in one or both eyes (<a href="#30" class="mim-tip-reference" title="Rice, D. S., Williams, R. W., Davisson, M. T., Harris, B., Goldowitz, D. <strong>A new mutant phenotype of retinal ganglion cell dysgenesis discovered in the mouse. (Abstract)</strong> Soc. Neurosci. Abst. 19: 51, 1993."None>Rice et al., 1993</a>). The basis of this phenotype is a unilateral or bilateral atrophy of the optic nerve. As in humans with optic atrophy-1, the severity of the atrophy of the optic nerves is highly variable, ranging from a slight reduction in the number of ganglion cell axons in 1 optic nerve to a complete elimination of both optic nerves. The surface area of the retina and the appearance of the inner and outer nuclear layers are qualitatively normal. Bst maps to chromosome 16 of the mouse (<a href="#16" class="mim-tip-reference" title="Epstein, R., Davisson, M. T., Lehmann, K., Akeson, E. C., Cohn, M. <strong>Position of Igl-1, md, and Bst loci on chromosome 16 of the mouse.</strong> Immunogenetics 23: 78-83, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3082752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3082752</a>] [<a href="https://doi.org/10.1007/BF00377965" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3082752">Epstein et al., 1986</a>) in a region of homology to human chromosome 3 where the OPA1 gene is situated. <a href="#31" class="mim-tip-reference" title="Rice, D. S., Williams, R. W., Ward-Bailey, P., Johnson, K. R., Harris, B. S., Davisson, M. T., Goldowitz, D. <strong>Mapping the Bst mutation on mouse chromosome 16: a model for human optic atrophy.</strong> Mammalian Genome 6: 546-548, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8589526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8589526</a>] [<a href="https://doi.org/10.1007/BF00356174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8589526">Rice et al. (1995)</a> did a refined mapping of this region by backcross analysis and found that the order of homologous loci in the mouse and human chromosomal maps suggested that OPA1 and Bst mapped to different regions of the conserved segment. However, they stated that the mutations may still be in the same gene and the gene order may have become altered within this segment. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3082752+8589526" 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="#34" class="mim-tip-reference" title="Smith, R. S., John, S. W. M., Zabeleta, A., Davisson, M. T., Hawes, N. L., Chang, B. <strong>The Bst locus on mouse chromosome 16 is associated with age-related subretinal neovascularization.</strong> Proc. Nat. Acad. Sci. 97: 2191-2195, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10681427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10681427</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10681427[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.040531597" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10681427">Smith et al. (2000)</a> reported an angiogenic phenotype in heterozygous Bst mice that was age-related, clinically evident, and resembled human subretinal neovascularization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10681427" 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="#13" class="mim-tip-reference" title="Davies, V. J., Hollins, A. J., Piechota, M. J., Yip, W., Davies, J. R., White, K. E., Nicols, P. P., Boulton, M. E., Votruba, M. <strong>Opa1 deficiency in a mouse model of autosomal dominant optic atrophy impairs mitochondrial morphology, optic nerve structure and visual function.</strong> Hum. Molec. Genet. 16: 1307-1318, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17428816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17428816</a>] [<a href="https://doi.org/10.1093/hmg/ddm079" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17428816">Davies et al. (2007)</a> generated mutant mice carrying an ethylnitrosourea (ENU)-induced Q285X mutation in the Opa1 gene, resulting in a truncated protein. Western analysis showed that the mutation resulted in approximately 50% reduction in Opa1 protein in retina and all tissues. The homozygous mutation was embryonic lethal by 13.5 days postcoitum. Fibroblasts from adult heterozygotes showed an increase in mitochondrial fission and fragmentation. In addition, electron microscopy revealed the slow onset of optic nerve degeneration; reduced visual function in heterozygotes was demonstrated by optokinetic drum testing and the circadian running wheel. <a href="#13" class="mim-tip-reference" title="Davies, V. J., Hollins, A. J., Piechota, M. J., Yip, W., Davies, J. R., White, K. E., Nicols, P. P., Boulton, M. E., Votruba, M. <strong>Opa1 deficiency in a mouse model of autosomal dominant optic atrophy impairs mitochondrial morphology, optic nerve structure and visual function.</strong> Hum. Molec. Genet. 16: 1307-1318, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17428816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17428816</a>] [<a href="https://doi.org/10.1093/hmg/ddm079" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17428816">Davies et al. (2007)</a> concluded that the OPA1 GTPase contains crucial information required for the survival of retinal ganglion cells and that OPA1 is essential for early embryonic survival. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17428816" 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="seeAlso" class="mim-anchor"></a>
|
|
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<a href="#Brodrick1974" class="mim-tip-reference" title="Brodrick, J. D. <strong>Hereditary optic atrophy with onset in early childhood.</strong> Brit. J. Ophthal. 58: 817-822, 1974.">Brodrick (1974)</a>; <a href="#Kjer1959" class="mim-tip-reference" title="Kjer, P. <strong>Infantile Optic Atrophy with Dominant Mode of Inheritance.</strong> Copenhagen: Bogtrykkeriet Forum (pub.) 1959.">Kjer (1959)</a>; <a href="#Smith1972" class="mim-tip-reference" title="Smith, D. P. <strong>Diagnostic criteria in dominantly inherited juvenile optic atrophy: report of three new families.</strong> Am. J. Optom. Arch. Am. Acad. Optom. 49: 183-200, 1972.">Smith (1972)</a>
|
|
</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="Alexander2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Alexander, C., Votruba, M., Pesch, U. E. A., Thiselton, D. L., Mayer, S., Moore, A., Rodriguez, M., Kellner, U., Leo-Kottler, B., Auburger, G., Bhattacharya, S. S., Wissinger, B.
|
|
<strong>OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28.</strong>
|
|
Nature Genet. 26: 211-215, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11017080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11017080</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11017080" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/79944" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Amati-Bonneau2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Amati-Bonneau, P., Guichet, A., Olichon, A., Chevrollier, A., Viala, F., Miot, S., Ayuso, C., Odent, S., Arrouet, C., Verny, C., Calmels, M.-N., Simard, G., Belenguer, P., Wang, J., Puel, J.-L., Hamel, C., Malthiery, Y., Bonneau, D., Lenaers, G., Reynier, P.
|
|
<strong>OPA1 R445H mutation in optic atrophy associated with sensorineural deafness.</strong>
|
|
Ann. Neurol. 58: 958-963, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16240368/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16240368</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16240368" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.20681" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Ban2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ban, T., Heymann, J. A. W., Song, Z., Hinshaw, J. E., Chan, D. C.
|
|
<strong>OPA1 disease alleles causing dominant optic atrophy have defects in cardiolipin-stimulated GTP hydrolysis and membrane tubulation.</strong>
|
|
Hum. Molec. Genet. 19: 2113-2122, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20185555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20185555</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20185555[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=20185555" 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/ddq088" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Barboni2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Barboni, P., Carbonelli, M., Savini, G., Foscarini. B., Parisi, V., Valentino, M. L., Carta, A., De Negri, A., Sadun, F., Zeviani, M., Sadun, A. A., Schimpf, S., Wissinger, B., Carelli, V.
|
|
<strong>OPA1 mutations associated with dominant optic atrophy influence optic nerve head size.</strong>
|
|
Ophthalmology 117: 1547-1553, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20417568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20417568</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20417568" 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.2009.12.042" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Barboni2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Barboni, P., Savini, G., Parisi, V., Carbonelli, M., La Morgia, C., Maresca, A., Sadun, F., De Negri, A. M., Carta, A., Sadun, A. A., Carelli, V.
|
|
<strong>Retinal nerve fiber layer thickness in dominant optic atrophy.</strong>
|
|
Ophthalmology 118: 2076-2080, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21621262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21621262</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21621262" 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.2011.02.027" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Bonneau1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bonneau, D., Souied, E., Gerber, S., Rozet, J.-M., D'Haens, E., Journel, H., Plessis, G., Weissenbach, J., Munnich, A., Kaplan, J.
|
|
<strong>No evidence of genetic heterogeneity in dominant optic atrophy.</strong>
|
|
J. Med. Genet. 32: 951-953, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8825922/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8825922</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8825922" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.32.12.951" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Brodrick1974" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brodrick, J. D.
|
|
<strong>Hereditary optic atrophy with onset in early childhood.</strong>
|
|
Brit. J. Ophthal. 58: 817-822, 1974.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4433496/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4433496</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4433496" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/bjo.58.9.817" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Brown1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brown, J., Jr., Fingert, J. H., Taylor, C. M., Lake, M., Sheffield, V. C., Stone, E. M.
|
|
<strong>Clinical and genetic analysis of a family affected with dominant optic atrophy (OPA1).</strong>
|
|
Arch. Ophthal. 115: 95-99, 1997. Note: Erratum: Arch. Ophthal. 115: 663 only, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9006432/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9006432</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9006432" 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.1997.01100150097016" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Caldwell1971" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Caldwell, J. B. H., Howard, R. O., Riggs, L. A.
|
|
<strong>Dominant juvenile optic atrophy. A study of two families and review of hereditary disease in childhood.</strong>
|
|
Arch. Ophthal. 85: 133-147, 1971.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5545713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5545713</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5545713" 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.1971.00990050135004" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Chen2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, A. S., Kovach, M. J., Herman, K., Avakian, A., Frank, W., Forrester, S., Lin, J.-P., Kimonis, V.
|
|
<strong>Clinical heterogeneity in autosomal dominant optic atrophy in two 3q28-qter linked central Illinois families.</strong>
|
|
Genet. Med. 2: 283-289, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11399209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11399209</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11399209" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/00125817-200009000-00003" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Chevrollier2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chevrollier, A., Guillet, V., Loiseau, D., Gueguen, N., de Crescenzo, M.-A. P., Verny, C., Ferre, M., Dollfus, H., Odent, S., Milea, D., Goizet, C., Amati-Bonneau, P., Procaccio, V., Bonneau, D., Reynier, P.
|
|
<strong>Hereditary optic neuropathies share a common mitochondrial coupling defect.</strong>
|
|
Ann. Neurol. 63: 794-798, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18496845/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18496845</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18496845" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.21385" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Cohn2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cohn, A. C., Toomes, C., Potter, C., Towns, K. V., Hewitt, A. W., Inglehearn, C. F., Craig, J. E., Mackey, D. A.
|
|
<strong>Autosomal dominant optic atrophy: penetrance and expressivity in patients with OPA1 mutations.</strong>
|
|
Am. J. Ophthal. 143: 656-662, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17306754/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17306754</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17306754" 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.ajo.2006.12.038" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Davies2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Davies, V. J., Hollins, A. J., Piechota, M. J., Yip, W., Davies, J. R., White, K. E., Nicols, P. P., Boulton, M. E., Votruba, M.
|
|
<strong>Opa1 deficiency in a mouse model of autosomal dominant optic atrophy impairs mitochondrial morphology, optic nerve structure and visual function.</strong>
|
|
Hum. Molec. Genet. 16: 1307-1318, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17428816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17428816</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17428816" 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/ddm079" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Delettre2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Delettre, C., Lenaers, G., Griffoin, J.-M., Gigarel, N., Lorenzo, C., Belenguer, P., Pelloquin, L., Grosgeorge, J., Turc-Carel, C., Perret, E., Astarie-Dequeker, C., Lasquellec, L., Arnaud, B., Ducommun, B., Kaplan, J., Hamel, C. P.
|
|
<strong>Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy.</strong>
|
|
Nature Genet. 26: 207-210, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11017079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11017079</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11017079" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/79936" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Eiberg1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eiberg, H., Kjer, B., Kjer, P., Rosenberg, T.
|
|
<strong>Dominant optic atrophy (OPA1) mapped to chromosome 3q region. I. Linkage analysis.</strong>
|
|
Hum. Molec. Genet. 3: 977-980, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951248</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951248" 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/3.6.977" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Epstein1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Epstein, R., Davisson, M. T., Lehmann, K., Akeson, E. C., Cohn, M.
|
|
<strong>Position of Igl-1, md, and Bst loci on chromosome 16 of the mouse.</strong>
|
|
Immunogenetics 23: 78-83, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3082752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3082752</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3082752" 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/BF00377965" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Fournier2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fournier, A. V., Damji, K. F., Epstein, D. L., Pollock, S. C.
|
|
<strong>Disc excavation in dominant optic atrophy.</strong>
|
|
Ophthalmology 108: 1595-1602, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11535456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11535456</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11535456" 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/s0161-6420(01)00696-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Fuhrmann2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fuhrmann, N., Alavi, M. V., Bitoun, P., Woernle, S., Auburger, G., Leo-Kottler, B., Yu-Wai-Man, P., Chinnery, P., Wissinger, B.
|
|
<strong>Genomic rearrangements in OPA1 are frequent in patients with autosomal dominant optic atrophy.</strong>
|
|
J. Med. Genet. 46: 136-144, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19181907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19181907</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19181907" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2008.062570" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Iverson1958" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Iverson, H. A.
|
|
<strong>Hereditary optic atrophy.</strong>
|
|
AMA Arch. Ophthal. 59: 850-853, 1958.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13532092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13532092</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13532092" 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.1958.00940070064006" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Johnston1979" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Johnston, P. B., Gaster, R. N., Smith, V. C., Tripathi, R. C.
|
|
<strong>A clinicopathologic study of autosomal dominant optic atrophy.</strong>
|
|
Am. J. Ophthal. 88: 868-875, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/315716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">315716</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=315716" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0002-9394(79)90565-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Johnston1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Johnston, R. L., Burdon, M. A., Spalton, D. J., Bryant, S. P., Behnam, J. T., Seller, M. J.
|
|
<strong>Dominant optic atrophy, Kjer type: linkage analysis and clinical features in a large British pedigree.</strong>
|
|
Arch. Ophthal. 115: 100-103, 1997. Note: Erratum: Arch. Ophthal. 115: 681 only, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9006433/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9006433</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9006433" 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.1997.01100150102017" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Johnston1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Johnston, R. L., Seller, M. J., Behnam, J. T., Burdon, M. A., Spalton, D. J.
|
|
<strong>Dominant optic atrophy: refining the clinical diagnostic criteria in light of genetic linkage studies.</strong>
|
|
Ophthalmology 106: 123-128, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9917792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9917792</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9917792" 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/S0161-6420(99)90013-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Kim2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kim, J. Y., Hwang, J.-M., Ko, H. S., Seong, M.-W., Park, B.-J., Park, S. S.
|
|
<strong>Mitochondrial DNA content is decreased in autosomal dominant optic atrophy.</strong>
|
|
Neurology 64: 966-972, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15781809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15781809</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15781809" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.WNL.0000157282.76715.B1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Kivlin1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kivlin, J. D., Lovrien, E. W., Bishop, D. T., Maumenee, I. H.
|
|
<strong>Linkage analysis in dominant optic atrophy.</strong>
|
|
Am. J. Hum. Genet. 35: 1190-1195, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6580816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6580816</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6580816" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Kjer1959" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kjer, P.
|
|
<strong>Infantile Optic Atrophy with Dominant Mode of Inheritance.</strong>
|
|
Copenhagen: Bogtrykkeriet Forum (pub.) 1959.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Lodi2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lodi, R., Tonon, C., Valentino, M. L., Iotti, S., Clementi, V., Malucelli, E., Barboni, P., Longanesi, L., Schimpf, S., Wissinger, B., Baruzzi, A., Barbiroli, B., Carelli, V.
|
|
<strong>Deficit of in vivo mitochondrial ATP production in OPA1-related dominant optic atrophy.</strong>
|
|
Ann. Neurol. 56: 719-723, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15505825/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15505825</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15505825" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.20278" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Lodi2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lodi, R., Tonon, C., Valentino, M. L., Manners, D., Testa, C., Malucelli, E., La Morgia, C., Barboni, P., Carbonelli, M., Schimpf, S., Wissinger, B., Zeviani, M., Baruzzi, A., Liguori, R., Barbiroli, B., Carelli, V.
|
|
<strong>Defective mitochondrial adenosine triphosphate production in skeletal muscle from patients with dominant optic atrophy due to OPA1 mutations.</strong>
|
|
Arch. Neurol. 68: 67-73, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20837821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20837821</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20837821" 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/archneurol.2010.228" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Lunkes1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lunkes, A., Hartung, U., Magarino, C., Rodriguez, M., Palmero, A., Rodriguez, L., Heredero, L., Weissenbach, J., Weber, J., Auburger, G.
|
|
<strong>Refinement of the OPA1 gene locus on chromosome 3q28-q29 to a region of 2-8 cM, in one Cuban pedigree with autosomal dominant optic atrophy type Kjer. (Letter)</strong>
|
|
Am. J. Hum. Genet. 57: 968-970, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7573062/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7573062</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7573062" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Payne2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Payne, M., Yang, Z., Katz, B. J., Warner, J. E. A., Weight, C. J., Zhao, Y., Pearson, E. D., Treft, R. L., Hillman, T., Kennedy, R. J., Meire, F. M., Zhang, K.
|
|
<strong>Dominant optic atrophy, sensorineural hearing loss, ptosis, and ophthalmoplegia: a syndrome caused by a missense mutation in OPA1.</strong>
|
|
Am. J. Ophthal. 138: 749-755, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15531309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15531309</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15531309" 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.ajo.2004.06.011" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Rice1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rice, D. S., Williams, R. W., Davisson, M. T., Harris, B., Goldowitz, D.
|
|
<strong>A new mutant phenotype of retinal ganglion cell dysgenesis discovered in the mouse. (Abstract)</strong>
|
|
Soc. Neurosci. Abst. 19: 51, 1993.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Rice1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rice, D. S., Williams, R. W., Ward-Bailey, P., Johnson, K. R., Harris, B. S., Davisson, M. T., Goldowitz, D.
|
|
<strong>Mapping the Bst mutation on mouse chromosome 16: a model for human optic atrophy.</strong>
|
|
Mammalian Genome 6: 546-548, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8589526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8589526</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8589526" 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/BF00356174" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Seller1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Seller, M. J., Behnam, J. T., Lewis, C. M., Johnston, R. L., Burdon, M. A., Spalton, D. J.
|
|
<strong>Linkage studies in dominant optic atrophy, Kjer type: possible evidence for heterogeneity.</strong>
|
|
J. Med. Genet. 34: 967-972, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9429135/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9429135</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9429135" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.34.12.967" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Smith1972" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Smith, D. P.
|
|
<strong>Diagnostic criteria in dominantly inherited juvenile optic atrophy: report of three new families.</strong>
|
|
Am. J. Optom. Arch. Am. Acad. Optom. 49: 183-200, 1972.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4502353/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4502353</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4502353" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/00006324-197203000-00001" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Smith2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Smith, R. S., John, S. W. M., Zabeleta, A., Davisson, M. T., Hawes, N. L., Chang, B.
|
|
<strong>The Bst locus on mouse chromosome 16 is associated with age-related subretinal neovascularization.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 2191-2195, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10681427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10681427</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10681427[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=10681427" 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.040531597" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Snell1897" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Snell, S.
|
|
<strong>Diseases of the optic nerve. I. Hereditary or congenital optic atrophy and allied cases.</strong>
|
|
Trans. Ophthal. Soc. U.K. 17: 66-81, 1897.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Stendahl-Brodin1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stendahl-Brodin, L., Moller, E., Link, H.
|
|
<strong>Hereditary optic atrophy with probable association with a specific HLA haplotype.</strong>
|
|
J. Neurol. Sci. 38: 11-21, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/151734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">151734</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=151734" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0022-510x(78)90241-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Votruba1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Votruba, M., Fitzke, F. W., Holder, G. E., Carter, A., Bhattacharya, S. S., Moore, A. T.
|
|
<strong>Clinical features in affected individuals from 21 pedigrees with dominant optic atrophy.</strong>
|
|
Arch. Ophthal. 116: 351-358, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9514489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9514489</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9514489" 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.116.3.351" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Votruba1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Votruba, M., Moore, A. T., Bhattacharya, S. S.
|
|
<strong>Genetic refinement of dominant optic atrophy (OPA1) locus to within a 2 cM interval of chromosome 3q.</strong>
|
|
J. Med. Genet. 34: 117-121, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9039986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9039986</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9039986" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.34.2.117" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Votruba1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Votruba, M., Moore, A. T., Bhattacharya, S. S.
|
|
<strong>Demonstration of a founder effect and fine mapping of dominant optic atrophy locus on 3q28-qter by linkage disequilibrium method: a study of 38 British Isles pedigrees.</strong>
|
|
Hum. Genet. 102: 79-86, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9490303/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9490303</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9490303" 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/s004390050657" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Votruba1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Votruba, M., Payne, A., Moore, A. T., Bhattacharya, S. S.
|
|
<strong>Dominant optic atrophy: exclusion and fine genetic mapping of the candidate gene, HRY.</strong>
|
|
Mammalian Genome 9: 784-787, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9745030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9745030</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9745030" 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/s003359900867" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Yu-Wai-Man2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yu-Wai-Man, P., Griffiths, P. G., Burke, A., Sellar, P. W., Clarke, M. P., Gnanaraj, L., Ah-Kine, D., Hudson, G., Czermin, B., Taylor, R. W., Horvath, R., Chinnery, P. F.
|
|
<strong>The prevalence and natural history of dominant optic atrophy due to OPA1 mutations.</strong>
|
|
Ophthalmology 117: 1538-1546, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20417570/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20417570</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20417570[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=20417570" 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.2009.12.038" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Yu-Wai-Man2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yu-Wai-Man, P., Griffiths, P. G., Gorman, G. S., Lourenco, C. M., Wright, A. F., Auer-Grumbach, M., Toscano, A., Musumeci, O., Valentino, M. L., Caporali, L., Lamperti, C., Tallaksen, C. M., and 24 others.
|
|
<strong>Multi-system neurological disease is common in patients with OPA1 mutations.</strong>
|
|
Brain 133: 771-786, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20157015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20157015</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20157015[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=20157015" 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/brain/awq007" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Yu-Wai-Man2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yu-Wai-Man, P., Griffiths, P. G., Hudson, G., Chinnery, P. F.
|
|
<strong>Inherited mitochondrial optic neuropathies.</strong>
|
|
J. Med. Genet. 46: 145-158, 2009. Note: Erratum: J. Med. Genet. 48: 284 only, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19001017/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19001017</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19001017[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=19001017" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2007.054270" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Yu-Wai-Man2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yu-Wai-Man, P., Sitarz, K. S., Samuels, D. C., Griffiths, P. G., Reeve, A. K., Bindoff, L. A., Horvath, R., Chinnery, P. F.
|
|
<strong>OPA1 mutations cause cytochrome c oxidase deficiency due to loss of wild-type mtDNA molecules.</strong>
|
|
Hum. Molec. Genet. 19: 3043-3052, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20484224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20484224</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20484224[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=20484224" 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/ddq209" 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">
|
|
Marla J. F. O'Neill - updated : 10/24/2023
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
George E. Tiller - updated : 8/27/2013<br>George E. Tiller - updated : 8/16/2013<br>Jane Kelly - updated : 2/20/2012<br>Jane Kelly - updated : 2/16/2012<br>Cassandra L. Kniffin - updated : 5/19/2011<br>Cassandra L. Kniffin - updated : 6/1/2009<br>Cassandra L. Kniffin - updated : 2/5/2009<br>Jane Kelly - updated : 10/30/2007<br>Marla J. F. O'Neill - updated : 1/19/2007<br>Cassandra L. Kniffin - updated : 3/3/2006<br>Marla J. F. O'Neill - updated : 10/25/2005<br>Cassandra L. Kniffin - updated : 6/29/2005<br>Jane Kelly - updated : 6/23/2005<br>Cassandra L. Kniffin - updated : 4/28/2005<br>Jane Kelly - updated : 2/25/2003<br>Jane Kelly - updated : 10/11/2002<br>Victor A. McKusick - updated : 7/18/2001<br>Victor A. McKusick - updated : 3/16/2000<br>Victor A. McKusick - updated : 6/3/1999<br>Victor A. McKusick - updated : 10/5/1998<br>Ada Hamosh - updated : 5/13/1998<br>Victor A. McKusick - updated : 4/30/1998<br>Victor A. McKusick - updated : 3/25/1997<br>Victor A. McKusick - updated : 3/6/1997
|
|
</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">
|
|
Victor A. McKusick : 6/2/1986
|
|
</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 : 04/11/2024
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 11/21/2023<br>carol : 11/20/2023<br>carol : 10/24/2023<br>alopez : 05/11/2022<br>carol : 09/03/2020<br>ckniffin : 08/19/2020<br>carol : 08/14/2020<br>carol : 08/13/2020<br>ckniffin : 08/10/2020<br>carol : 07/16/2018<br>carol : 07/13/2018<br>carol : 12/12/2017<br>carol : 11/09/2017<br>alopez : 11/08/2017<br>ckniffin : 11/07/2017<br>carol : 01/20/2017<br>ckniffin : 01/17/2017<br>carol : 11/20/2015<br>ckniffin : 11/18/2015<br>alopez : 4/2/2015<br>mcolton : 4/1/2015<br>ckniffin : 3/31/2015<br>carol : 8/28/2014<br>carol : 4/11/2014<br>alopez : 8/28/2013<br>tpirozzi : 8/28/2013<br>tpirozzi : 8/27/2013<br>carol : 8/19/2013<br>tpirozzi : 8/19/2013<br>tpirozzi : 8/19/2013<br>tpirozzi : 8/16/2013<br>tpirozzi : 8/16/2013<br>tpirozzi : 8/16/2013<br>tpirozzi : 8/16/2013<br>tpirozzi : 8/16/2013<br>carol : 4/1/2013<br>terry : 12/20/2012<br>terry : 10/10/2012<br>alopez : 2/20/2012<br>alopez : 2/16/2012<br>wwang : 6/20/2011<br>ckniffin : 5/19/2011<br>wwang : 2/3/2011<br>alopez : 8/31/2009<br>wwang : 6/9/2009<br>ckniffin : 6/1/2009<br>wwang : 4/1/2009<br>ckniffin : 3/26/2009<br>alopez : 2/23/2009<br>wwang : 2/17/2009<br>ckniffin : 2/5/2009<br>carol : 10/30/2007<br>carol : 1/23/2007<br>carol : 1/22/2007<br>terry : 1/19/2007<br>carol : 3/10/2006<br>carol : 3/10/2006<br>ckniffin : 3/9/2006<br>ckniffin : 3/9/2006<br>ckniffin : 3/3/2006<br>alopez : 12/9/2005<br>carol : 10/25/2005<br>wwang : 7/14/2005<br>wwang : 7/13/2005<br>ckniffin : 6/29/2005<br>alopez : 6/23/2005<br>wwang : 5/10/2005<br>ckniffin : 4/28/2005<br>carol : 2/25/2003<br>carol : 2/25/2003<br>cwells : 10/11/2002<br>carol : 1/2/2002<br>mcapotos : 8/8/2001<br>terry : 7/18/2001<br>carol : 11/17/2000<br>alopez : 9/28/2000<br>alopez : 9/26/2000<br>alopez : 9/26/2000<br>alopez : 9/26/2000<br>mcapotos : 4/12/2000<br>terry : 3/16/2000<br>jlewis : 6/9/1999<br>terry : 6/3/1999<br>carol : 10/7/1998<br>terry : 10/5/1998<br>alopez : 5/13/1998<br>carol : 5/11/1998<br>carol : 5/5/1998<br>terry : 4/30/1998<br>alopez : 3/25/1997<br>alopez : 3/25/1997<br>alopez : 3/25/1997<br>terry : 3/17/1997<br>mark : 3/6/1997<br>terry : 3/4/1997<br>mark : 1/20/1996<br>mark : 1/19/1996<br>terry : 10/20/1995<br>mark : 10/2/1995<br>mimadm : 12/2/1994<br>jason : 7/25/1994<br>carol : 10/19/1992<br>supermim : 3/16/1992
|
|
</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> 165500
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
OPTIC ATROPHY 1; OPA1
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div >
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
OPTIC ATROPHY, JUVENILE<br />
|
|
KJER-TYPE OPTIC ATROPHY<br />
|
|
OPTIC ATROPHY, KJER TYPE; OAK
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 717336005;
|
|
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 98673;
|
|
|
|
|
|
<strong>DO:</strong> 0111441;
|
|
|
|
|
|
</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">
|
|
3q29
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Optic atrophy 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
165500
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
OPA1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
605290
|
|
</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 optic atrophy-1 (OPA1) is caused by heterozygous mutation in the gene encoding the human homolog of the S. pombe dynamin-related protein Msp1 (OPA1; 605290) on chromosome 3q29.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Autosomal dominant optic atrophy is characterized by an insidious onset of visual impairment in early childhood with moderate to severe loss of visual acuity, temporal optic disc pallor, color vision deficits, and centrocecal scotoma of variable density (Votruba et al., 1998). </p><p>Some patients with mutations in the OPA1 gene may also develop extraocular neurologic features, such as deafness, progressive external ophthalmoplegia, muscle cramps, hyperreflexia, and ataxia; see 125250. There appears to be a wide range of intermediate phenotypes (Yu-Wai-Man et al., 2010). </p><p>Yu-Wai-Man et al. (2009) provided a detailed review of autosomal dominant optic atrophy and Leber hereditary optic neuropathy (LHON; 535000), with emphasis on the selective vulnerability of retinal ganglion cells to mitochondrial dysfunction in both disorders. </p><p><strong><em>Genetic Heterogeneity of Optic Atrophy</em></strong></p><p>
|
|
Also see optic atrophy-2 (OPA2; 311050), mapped to chromosome Xp11.4-p11.21; OPA3 (165300), caused by mutation in the OPA3 gene (606580) on chromosome 19q13; OPA4 (605293), mapped to chromosome 18q12.2-q12.3; OPA5 (610708), caused by mutation in the DNM1L gene (603850) on chromosome 12p11; OPA6 (258500), mapped to chromosome 8q21-q22; OPA7 (612989), caused by mutation in the TMEM126A gene (612988) on chromosome 11q14; OPA8 (616648), mapped to chromosome 16q21-q22; OPA9 (616289), caused by mutation in the ACO2 gene (100850) on chromosome 22q13; OPA10 (616732), caused by mutation in the RTN4IP1 gene (610502) on chromosome 6q21; OPA11 (617302), caused by mutation in the YME1L1 gene (607472) on chromosome 10p12; OPA12 (618977), caused by mutation in the AFG3L2 gene (604581) on chromosome 18p11; OPA13 (165510), caused by mutation in the SSBP1 gene (600439) on chromosome 7q34; OPA14 (620550), caused by mutation in the MIEF1 gene (615497) on chromosome 22q13; OPA15 (620583), caused by mutation in the MCAT gene (614479) on chromosome 22q13; and OPA16 (620629), caused by mutation in the MECR gene (608205) on chromosome 1p35.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Iverson (1958) reported congenital optic atrophy in 3 generations. The clear autosomal dominant pattern of inheritance and congenital nature distinguished it from Leber hereditary optic atrophy (LHON; 535000). </p><p>Caldwell et al. (1971) described 2 families with insidious onset of optic atrophy in childhood. There were no neurologic, congenital, or developmental abnormalities. Caldwell et al. (1971) classified the familial optic atrophies into 6 groups: congenital dominant, congenital recessive, juvenile dominant, juvenile recessive, Leber, and autosomal recessive Behr syndrome (210000). The features of the 6 groups were usefully compared. Snell (1897) is generally credited with first describing a form of optic atrophy separate from Leber optic atrophy. Stendahl-Brodin et al. (1978) described a family with probable autosomal dominant inheritance of late-onset optic atrophy. Linkage to HLA was suggested. Johnston et al. (1979) studied an extensively affected kindred and had an opportunity for histologic examination of the eyes of an affected 56-year-old woman. Her vision had been severely reduced since childhood. Pathologic changes were diffuse atrophy of the ganglion cell layer of the retina and loss of myelin and nerve tissue within the optic nerve. They suggested that the disorder is a primary degeneration of retinal ganglion cells. Most affected members of the family had severe unclassified color defects. </p><p>Eiberg et al. (1994) described autosomal dominant optic atrophy as being characterized by an insidious onset of optic atrophy in early childhood with moderate to severe decrease of visual acuity, blue-yellow dyschromatopsia, and centrocecal scotoma of varying density. Many affected members of the families may be unaware of having the disease or of its hereditary aspects. </p><p>Votruba et al. (1998) evaluated the clinical features in 21 families with 3q-linked dominant optic atrophy. They found wide intra- and interfamilial phenotypic variation, with visual function deteriorating with age in only some families. There was evidence of degeneration of the ganglion cell layer, predominantly from central retina, but this was not the exclusive result of either parvocellular or magnocellular cell loss. </p><p>Johnston et al. (1999) refined the clinical diagnostic criteria for dominant optic atrophy on the basis of linkage studies, i.e., the study of subjects who had been classified clinically as definitely or possibly affected on the basis of a domiciliary examination before genetic analysis, and the comparison of these results with the haplotype analysis. Clinically, 43 subjects were identified as definitely affected, 4 as possibly affected, and 45 as unaffected. Visual acuity in affected subjects ranged from 6/6 to count fingers and declined with age. On genetic analysis, a specific haplotype was identified in each family, which was found in all definitely affected members but not in those regarded as unaffected. The 4 possibly affected individuals also bore the haplotype that segregated with the disorder. Contrary to accepted criteria, symptoms began before the age of 10 years in only 58% of affected individuals. Visual acuity in affected subjects was highly variable. A mild degree of temporal or diffuse pallor of the optic disc and minimal color vision defects, in the context of the family with dominant optic atrophy, were highly suggestive of an individual being affected, even if visual acuity was normal. </p><p>In 2 large U.S. midwestern families with autosomal dominant optic atrophy, Chen et al. (2000) showed linkage to 3q28-q29 and pointed out considerable intrafamilial phenotypic variation as well as sex-influenced severity. Visual loss among affected males was more severe than among affected females. </p><p>Fournier et al. (2001) examined optic disc morphology in patients with dominant optic atrophy to elucidate features that would distinguish dominant optic atrophy from normal tension glaucoma (606657). The optic atrophy patients had a mild to moderate reduction in visual acuity and color vision. Seventy-eight percent had a temporal wedge-shaped area of optic disc excavation. All involved eyes had moderate to severe pallor of the temporal neuroretinal rim, with milder pallor of the remaining noncupped rim. All eyes had a slate-gray crescent within the neuroretinal rim tissue and some degree of peripapillary atrophy. The authors concluded that several clinical features, including early age of onset, preferential loss of central vision, sparing of the peripheral fields, pallor of the remaining neuroretinal rim, and a family history of unexplained visual loss or optic atrophy, help distinguish patients with dominant optic atrophy from those with normal tension glaucoma. </p><p>To analyze the influence of OPA1 gene mutations on optic nerve head morphology in patients with dominant optic atrophy, Barboni et al. (2010) studied the optic nerve head of 28 OPA1 mutation-positive patients from 11 pedigrees and 56 age-matched controls by optical coherence tomography (OCT). Patients showed a significantly smaller optic disc area (P less than 0.0001), and vertical (P = 0.018), and horizontal (P less than 0.0001) disc diameters, compared with controls. Stratification of the results for the single OPA1 mutation revealed normal optic nerve head area with 2 mutations, whereas a missense mutation linked to a 'dominant optic atrophy plus' phenotype (605290.0017) had the smallest ONH measurements. Barboni et al. (2010) concluded that their observations suggested a theretofore unrecognized role for OPA1 in eye development, and in particular in modeling optic nerve head size and conformation. </p><p>Using optical coherence tomography (OCT), Barboni et al. (2011) compared the retinal nerve fiber layers (RNFLs) of 33 dominant optic atrophy patients with those of 43 healthy control subjects matched for age and optic nerve head size. They found that patients had significant RNFL thickness reduction in all quadrants, with a preferential involvement of the temporal and inferior sectors. The progressive decline in RNFL thickness with age was similar to that observed in healthy subjects and was more evident in the 2 quadrants with higher residual amounts of fibers, i.e., the superior and inferior quadrants. The temporal quadrant was profoundly depleted of fiber so that the further rate of loss of microns per year was close to zero, whereas the nasal quadrant was spared the most by neurodegeneration. Barboni et al. (2011) concluded that these findings, together with their description of small optic nerve head size in dominant optic atrophy (Barboni et al., 2010), strongly suggested that patients with this disease are born with fewer optic nerve axons and supported the hypothesis that subsequent visual loss depends on further age-related loss of fibers, which also occurred in controls. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The transmission pattern of OPA1 in the families reported by Cohn et al. (2007) was consistent with autosomal dominant inheritance. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Pathogenesis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The pathogenic characteristics of OPA1 resemble those of Leber hereditary optic neuropathy (535000), which results from a defect of the mitochondrion. Mutations in the mitochondrial gene responsible presumably lead to insufficient energy supply in the highly energy-demanding neurons of the optic nerve, notably the papillomacular bundle, and cause blindness by a compromise of axonal transport in retinal ganglion cells. Alexander et al. (2000) hypothesized that mutations in the OPA1 gene affect mitochondrial integrity, resulting in an impairment of energy supply. </p><p>Using phosphorus magnetic resonance spectroscopy, Lodi et al. (2004) demonstrated defective oxidative phosphorylation in 6 OPA1 patients from 2 unrelated families with a 4-bp deletion in the OPA1 gene (605290.0003). The time constant of postexercise phosphocreatine resynthesis was significantly increased in patients compared to controls, indicating a reduced rate of mitochondrial ATP production in the patients. Lodi et al. (2004) noted that similar findings had been observed in patients with LHON. Lodi et al. (2011) performed similar studies as Lodi et al. (2004) 18 patients, including 6 previously reported by Lodi et al. (2004), with genetically confirmed OPA1 due to different mutations. Sixteen patients carried truncating mutations resulting in haploinsufficiency, and 2 patients had missense mutations. Calf muscles from patients showed reduced phosphorylation potential in patients at rest, indicating reduced energy reserve, although only 4 patients had levels below the normal range. Patients showed shorter exercise duration compared to controls, indicating reduced oxidative capacity. Postexercise skeletal muscle Vmax of mitochondrial ATP synthesis was reduced by 36% in patients compared to controls, and only 2 patients had normal Vmax levels. Four of 10 patients had increased serum lactate after exercise. Despite these defects, muscle biopsies available from 5 patients did not show clear-cut hallmarks of mitochondrial myopathy, such as ragged-red fibers, and there was not clear evidence of mtDNA deletions. </p><p>Payne et al. (2004) hypothesized that although OPA1 is a nuclear gene, the fact that the gene product localizes to mitochondria suggests that mitochondrial dysfunction might be the final common pathway for many forms of syndromic and nonsyndromic optic atrophy, hearing loss, and external ophthalmoplegia. </p><p>Using quantitative real-time PCR, Kim et al. (2005) found significantly decreased levels of cellular mtDNA in blood from 4 of 8 patients with OPA1 (range, 412.0 to 648.0 copies per cell) compared to controls (1,148.6 +/- 406.9). Three patients had decreased levels (813.2 to 1,133.6), and 1 patient had normal levels (1,455.3). The findings were consistent with the hypothesis that OPA1 gene mutations result in decreased numbers of mitochondrial organelles via apoptosis. However, neither mtDNA content nor genotype correlated with phenotype, indicating that additional epigenetic factors are involved. Kim et al. (2005) postulated that selective damage to retinal ganglion cells in OPA1 may result from a combination of high energy requirements of retinal cells in the macular area and increased sensitivity of retinal ganglial cells to free radicals and oxidative stress. </p><p>Amati-Bonneau et al. (2005) found fragmentation of the mitochondrial network and defects in oxidative phosphorylation in skin fibroblasts from patients with optic atrophy and deafness. </p><p>In fibroblasts derived from 16 patients with hereditary optic neuropathy, including either LHON, OPA1, or OPA3, Chevrollier et al. (2008) found a common coupling defect of oxidative phosphorylation, resulting in reduced efficiency of ATP synthesis. LHON fibroblasts showed a mean decrease of 39% in complex I activity compared to controls. OPA1 and OPA3 fibroblasts showed normal complex I activities, but a mean decrease of 25% in complex IV activity and a mean 60% increase in complex V activity. Resting respiration was about twice as high in all LHON, OPA1, and OPA3 fibroblasts compared to controls, reflecting a proton leak or electron slip. However, all mutant cell lines used a greater proportion of routine respiratory capacity during routine compared to controls, suggesting a compensatory mechanism. The energy defect was most pronounced in fibroblasts from patients with additional neurologic symptoms. </p><p>Yu-Wai-Man et al. (2010) investigated the mtDNA changes induced by OPA1 mutations in skeletal muscle biopsies from 15 patients with both isolated DOA and neuromuscularly impaired (DOA+; 125250) phenotypes. There was a 2- to 4-fold increase in mtDNA copy number at the single-fiber level, and patients with DOA+ features had significantly greater mtDNA proliferation in their cytochrome c oxidase (COX; see 516030)-negative skeletal muscle fibers compared to patients with isolated optic neuropathy. Low levels of wildtype mtDNA molecules were present in COX-deficient muscle fibers from both isolated DOA and DOA+ patients, implicating haploinsufficiency as the mechanism responsible for the biochemical defect. The authors proposed a 'maintenance of wildtype' hypothesis, with secondary mtDNA deletions induced by OPA1 mutations triggering a compensatory mitochondrial proliferative response in order to maintain an optimal level of wildtype mtDNA genomes. However, when deletion levels reach a critical level, further mitochondrial proliferation may lead to replication of the mutant species at the expense of wildtype mtDNA, resulting in the loss of respiratory chain COX activity. </p><p>Ban et al. (2010) showed that OPA1 has a low basal rate of GTP hydrolysis that is dramatically enhanced by association with liposomes containing negative phospholipids, such as cardiolipin. Lipid association triggered assembly of OPA1 into higher order oligomers. In addition, OPA1 could promote the protrusion of lipid tubules from the surface of cardiolipin-containing liposomes. In such lipid protrusions, OPA1 assemblies were observed on the outside of the lipid tubule surface, a protein-membrane topology similar to that of classical dynamins. The membrane tubulation activity of OPA1 was suppressed by GTP-gamma-S. OPA1 disease alleles associated with dominant optic atrophy displayed selective defects in several activities, including cardiolipin association, GTP hydrolysis, and membrane tubulation. Ban et al. (2010) concluded that interaction of OPA1 with membranes can stimulate higher order assembly, enhance GTP hydrolysis, and lead to membrane deformation into tubules. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In a population-based epidemiologic study of autosomal dominant optic atrophy in the north of England, Yu-Wai-Man et al. (2010) determined that the minimum point prevalence was 2.87 per 100,000, or approximately 1 in 35,000. The point prevalence was 2.09 per 100,000 when only OPA1-positive cases were considered. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By linkage studies in 3 extended Danish pedigrees using highly informative short tandem repeat polymorphisms, Eiberg et al. (1994) found linkage of the disease gene, which they symbolized OPA1, to a (CA)n dinucleotide repeat polymorphism at locus D3S1314; maximum lod = 10.34 at theta = 0.075. Using 2 additional chromosome 3 markers, they mapped the OPA1 gene in the region between D3S1314 and D3S1265: 3q28-qter. Lunkes et al. (1995) refined the localization of the OPA1 gene on 3q28-q29 to a region of 2-8 cM by studies in a Cuban pedigree with autosomal dominant optic atrophy of the KJER type. </p><p>Bonneau et al. (1995) confirmed the mapping of optic atrophy-1 to 3q28-qter, showing close linkage of the disease locus to 3 newly reported microsatellite DNA markers in 4 French families. There was no evidence of genetic heterogeneity. </p><p>In a study of 5 British pedigrees, Votruba et al. (1997) confirmed linkage to 3q28-q29 and narrowed the assignment to a 2-cM segment. In a large family in which Brown et al. (1997) found 34 affected members, linkage analysis revealed significant lod scores with 9 markers on 3q. The highest lod score, 10.1, was obtained with marker D3S2305. Analysis of recombinants narrowed the disease interval to approximately 3.8 cM, flanked by D3S3669 (centromeric) and D3S1305 (telomeric). Most affected members experienced loss of vision in the first decade of life and most progressed to 20/800 or poorer visual acuity by age 60, although 2 patients maintained visual acuities of 20/40 at that age. Similarly, by linkage analysis in a British family with 16 affected members, Johnston et al. (1997) mapped the OPA1 gene to the 3q27-q28 region. Votruba et al. (1998) further narrowed the optic atrophy-1 linkage interval on chromosome 3q28 to within 400 kb of the marker D3S1523, with a multipoint analysis maximum lod score of 8.01. They studied a total of 38 families with dominant optic atrophy, unrelated on the basis of genealogy, from a database of genetic eye disease families originating from the British isles. Allelic frequency analysis and haplotype parsimony analysis showed evidence of founder effect in 36 of the 38 pedigrees. </p><p><strong><em>Heterogeneity</em></strong></p><p>
|
|
Heterogeneity within the group of autosomal dominant optic atrophy was suggested by linkage studies (Kivlin et al., 1983; Seller et al., 1997). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Alexander et al. (2000) and Delettre et al. (2000) independently identified a gene (OPA1; 605290) in the optic atrophy-1 candidate region that encodes a polypeptide with homology to dynamin-related GTPases. In patients with optic atrophy, both Alexander et al. (2000) and Delettre et al. (2000) identified mutations in the OPA1 gene (605290.0001-605290.0009). </p><p>Cohn et al. (2007) identified OPA1 mutations in 11 of 17 Australian pedigrees with autosomal dominant optic atrophy. The penetrance in the families with complete sib recruitment was 82.5%. </p><p>Using multiplex ligation probe amplification (MLPA), Fuhrmann et al. (2009) identified heterozygous deletions of 1 or more exons in the OPA1 gene in 5 of 42 OPA1 probands who did not have point mutations by previous screening techniques. Three additional probands had a heterozygous in-frame duplication of exons 7 to 9. Overall, the results were consistent with haploinsufficiency as the disease mechanism rather than gain of function. Fuhrmann et al. (2009) estimated that OPA1 genomic rearrangements have a prevalence of 12.9% in patients with autosomal dominant optic atrophy. </p><p>To define the prevalence and natural history of autosomal dominant optic atrophy, Yu-Wai-Man et al. (2010) performed a population-based epidemiologic and molecular study of 76 probands with a clinical diagnosis of autosomal dominant optic atrophy from the north of England. They detected OPA1 mutations in 57.6% of probands with a positive family history of optic atrophy (19/33) and in 14.0% of singleton cases (6/43). Approximately 2/3 of families with dominant optic atrophy harbored OPA1 mutations (14/22, 63%), and 5 novel OPA1 mutations were identified. Only 1 family carried a large-scale OPA1 rearrangement, and no OPA3 mutations were found in their optic atrophy cohort. OPA1 missense mutations were associated with a significantly worse visual outcome compared with other mutational subtypes (P = 0.0001). </p><p><strong><em>Exclusion Studies</em></strong></p><p>
|
|
Votruba et al. (1998) excluded the candidate gene HRY (139605) as the causative gene for OPA on chromosome 3q. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>'Belly spot and tail' (Bst) is a semidominant, homozygous lethal mutation in mouse that arose in the inbred strain C57BLKS (C57BL/Ks). Heterozygous mice have a kinky tail, white feet, and a white spot at the ventral midline. The phenotype arises from a deletion within the RPL24 (604180) riboprotein gene. In approximately 50% of the heterozygous mice, there is a reduction or a complete absence of the pupillary light reflex in one or both eyes (Rice et al., 1993). The basis of this phenotype is a unilateral or bilateral atrophy of the optic nerve. As in humans with optic atrophy-1, the severity of the atrophy of the optic nerves is highly variable, ranging from a slight reduction in the number of ganglion cell axons in 1 optic nerve to a complete elimination of both optic nerves. The surface area of the retina and the appearance of the inner and outer nuclear layers are qualitatively normal. Bst maps to chromosome 16 of the mouse (Epstein et al., 1986) in a region of homology to human chromosome 3 where the OPA1 gene is situated. Rice et al. (1995) did a refined mapping of this region by backcross analysis and found that the order of homologous loci in the mouse and human chromosomal maps suggested that OPA1 and Bst mapped to different regions of the conserved segment. However, they stated that the mutations may still be in the same gene and the gene order may have become altered within this segment. </p><p>Smith et al. (2000) reported an angiogenic phenotype in heterozygous Bst mice that was age-related, clinically evident, and resembled human subretinal neovascularization. </p><p>Davies et al. (2007) generated mutant mice carrying an ethylnitrosourea (ENU)-induced Q285X mutation in the Opa1 gene, resulting in a truncated protein. Western analysis showed that the mutation resulted in approximately 50% reduction in Opa1 protein in retina and all tissues. The homozygous mutation was embryonic lethal by 13.5 days postcoitum. Fibroblasts from adult heterozygotes showed an increase in mitochondrial fission and fragmentation. In addition, electron microscopy revealed the slow onset of optic nerve degeneration; reduced visual function in heterozygotes was demonstrated by optokinetic drum testing and the circadian running wheel. Davies et al. (2007) concluded that the OPA1 GTPase contains crucial information required for the survival of retinal ganglion cells and that OPA1 is essential for early embryonic survival. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Brodrick (1974); Kjer (1959); Smith (1972)
|
|
</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">
|
|
Alexander, C., Votruba, M., Pesch, U. E. A., Thiselton, D. L., Mayer, S., Moore, A., Rodriguez, M., Kellner, U., Leo-Kottler, B., Auburger, G., Bhattacharya, S. S., Wissinger, B.
|
|
<strong>OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28.</strong>
|
|
Nature Genet. 26: 211-215, 2000.
|
|
|
|
|
|
[PubMed: 11017080]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/79944]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Amati-Bonneau, P., Guichet, A., Olichon, A., Chevrollier, A., Viala, F., Miot, S., Ayuso, C., Odent, S., Arrouet, C., Verny, C., Calmels, M.-N., Simard, G., Belenguer, P., Wang, J., Puel, J.-L., Hamel, C., Malthiery, Y., Bonneau, D., Lenaers, G., Reynier, P.
|
|
<strong>OPA1 R445H mutation in optic atrophy associated with sensorineural deafness.</strong>
|
|
Ann. Neurol. 58: 958-963, 2005.
|
|
|
|
|
|
[PubMed: 16240368]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.20681]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ban, T., Heymann, J. A. W., Song, Z., Hinshaw, J. E., Chan, D. C.
|
|
<strong>OPA1 disease alleles causing dominant optic atrophy have defects in cardiolipin-stimulated GTP hydrolysis and membrane tubulation.</strong>
|
|
Hum. Molec. Genet. 19: 2113-2122, 2010.
|
|
|
|
|
|
[PubMed: 20185555]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddq088]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Barboni, P., Carbonelli, M., Savini, G., Foscarini. B., Parisi, V., Valentino, M. L., Carta, A., De Negri, A., Sadun, F., Zeviani, M., Sadun, A. A., Schimpf, S., Wissinger, B., Carelli, V.
|
|
<strong>OPA1 mutations associated with dominant optic atrophy influence optic nerve head size.</strong>
|
|
Ophthalmology 117: 1547-1553, 2010.
|
|
|
|
|
|
[PubMed: 20417568]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ophtha.2009.12.042]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Barboni, P., Savini, G., Parisi, V., Carbonelli, M., La Morgia, C., Maresca, A., Sadun, F., De Negri, A. M., Carta, A., Sadun, A. A., Carelli, V.
|
|
<strong>Retinal nerve fiber layer thickness in dominant optic atrophy.</strong>
|
|
Ophthalmology 118: 2076-2080, 2011.
|
|
|
|
|
|
[PubMed: 21621262]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ophtha.2011.02.027]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bonneau, D., Souied, E., Gerber, S., Rozet, J.-M., D'Haens, E., Journel, H., Plessis, G., Weissenbach, J., Munnich, A., Kaplan, J.
|
|
<strong>No evidence of genetic heterogeneity in dominant optic atrophy.</strong>
|
|
J. Med. Genet. 32: 951-953, 1995.
|
|
|
|
|
|
[PubMed: 8825922]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.32.12.951]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brodrick, J. D.
|
|
<strong>Hereditary optic atrophy with onset in early childhood.</strong>
|
|
Brit. J. Ophthal. 58: 817-822, 1974.
|
|
|
|
|
|
[PubMed: 4433496]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/bjo.58.9.817]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brown, J., Jr., Fingert, J. H., Taylor, C. M., Lake, M., Sheffield, V. C., Stone, E. M.
|
|
<strong>Clinical and genetic analysis of a family affected with dominant optic atrophy (OPA1).</strong>
|
|
Arch. Ophthal. 115: 95-99, 1997. Note: Erratum: Arch. Ophthal. 115: 663 only, 1997.
|
|
|
|
|
|
[PubMed: 9006432]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archopht.1997.01100150097016]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Caldwell, J. B. H., Howard, R. O., Riggs, L. A.
|
|
<strong>Dominant juvenile optic atrophy. A study of two families and review of hereditary disease in childhood.</strong>
|
|
Arch. Ophthal. 85: 133-147, 1971.
|
|
|
|
|
|
[PubMed: 5545713]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archopht.1971.00990050135004]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, A. S., Kovach, M. J., Herman, K., Avakian, A., Frank, W., Forrester, S., Lin, J.-P., Kimonis, V.
|
|
<strong>Clinical heterogeneity in autosomal dominant optic atrophy in two 3q28-qter linked central Illinois families.</strong>
|
|
Genet. Med. 2: 283-289, 2000.
|
|
|
|
|
|
[PubMed: 11399209]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00125817-200009000-00003]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chevrollier, A., Guillet, V., Loiseau, D., Gueguen, N., de Crescenzo, M.-A. P., Verny, C., Ferre, M., Dollfus, H., Odent, S., Milea, D., Goizet, C., Amati-Bonneau, P., Procaccio, V., Bonneau, D., Reynier, P.
|
|
<strong>Hereditary optic neuropathies share a common mitochondrial coupling defect.</strong>
|
|
Ann. Neurol. 63: 794-798, 2008.
|
|
|
|
|
|
[PubMed: 18496845]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.21385]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cohn, A. C., Toomes, C., Potter, C., Towns, K. V., Hewitt, A. W., Inglehearn, C. F., Craig, J. E., Mackey, D. A.
|
|
<strong>Autosomal dominant optic atrophy: penetrance and expressivity in patients with OPA1 mutations.</strong>
|
|
Am. J. Ophthal. 143: 656-662, 2007.
|
|
|
|
|
|
[PubMed: 17306754]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajo.2006.12.038]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Davies, V. J., Hollins, A. J., Piechota, M. J., Yip, W., Davies, J. R., White, K. E., Nicols, P. P., Boulton, M. E., Votruba, M.
|
|
<strong>Opa1 deficiency in a mouse model of autosomal dominant optic atrophy impairs mitochondrial morphology, optic nerve structure and visual function.</strong>
|
|
Hum. Molec. Genet. 16: 1307-1318, 2007.
|
|
|
|
|
|
[PubMed: 17428816]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddm079]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Delettre, C., Lenaers, G., Griffoin, J.-M., Gigarel, N., Lorenzo, C., Belenguer, P., Pelloquin, L., Grosgeorge, J., Turc-Carel, C., Perret, E., Astarie-Dequeker, C., Lasquellec, L., Arnaud, B., Ducommun, B., Kaplan, J., Hamel, C. P.
|
|
<strong>Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy.</strong>
|
|
Nature Genet. 26: 207-210, 2000.
|
|
|
|
|
|
[PubMed: 11017079]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/79936]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eiberg, H., Kjer, B., Kjer, P., Rosenberg, T.
|
|
<strong>Dominant optic atrophy (OPA1) mapped to chromosome 3q region. I. Linkage analysis.</strong>
|
|
Hum. Molec. Genet. 3: 977-980, 1994.
|
|
|
|
|
|
[PubMed: 7951248]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/3.6.977]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Epstein, R., Davisson, M. T., Lehmann, K., Akeson, E. C., Cohn, M.
|
|
<strong>Position of Igl-1, md, and Bst loci on chromosome 16 of the mouse.</strong>
|
|
Immunogenetics 23: 78-83, 1986.
|
|
|
|
|
|
[PubMed: 3082752]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00377965]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fournier, A. V., Damji, K. F., Epstein, D. L., Pollock, S. C.
|
|
<strong>Disc excavation in dominant optic atrophy.</strong>
|
|
Ophthalmology 108: 1595-1602, 2001.
|
|
|
|
|
|
[PubMed: 11535456]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0161-6420(01)00696-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fuhrmann, N., Alavi, M. V., Bitoun, P., Woernle, S., Auburger, G., Leo-Kottler, B., Yu-Wai-Man, P., Chinnery, P., Wissinger, B.
|
|
<strong>Genomic rearrangements in OPA1 are frequent in patients with autosomal dominant optic atrophy.</strong>
|
|
J. Med. Genet. 46: 136-144, 2009.
|
|
|
|
|
|
[PubMed: 19181907]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2008.062570]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Iverson, H. A.
|
|
<strong>Hereditary optic atrophy.</strong>
|
|
AMA Arch. Ophthal. 59: 850-853, 1958.
|
|
|
|
|
|
[PubMed: 13532092]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archopht.1958.00940070064006]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johnston, P. B., Gaster, R. N., Smith, V. C., Tripathi, R. C.
|
|
<strong>A clinicopathologic study of autosomal dominant optic atrophy.</strong>
|
|
Am. J. Ophthal. 88: 868-875, 1979.
|
|
|
|
|
|
[PubMed: 315716]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0002-9394(79)90565-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johnston, R. L., Burdon, M. A., Spalton, D. J., Bryant, S. P., Behnam, J. T., Seller, M. J.
|
|
<strong>Dominant optic atrophy, Kjer type: linkage analysis and clinical features in a large British pedigree.</strong>
|
|
Arch. Ophthal. 115: 100-103, 1997. Note: Erratum: Arch. Ophthal. 115: 681 only, 1997.
|
|
|
|
|
|
[PubMed: 9006433]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archopht.1997.01100150102017]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johnston, R. L., Seller, M. J., Behnam, J. T., Burdon, M. A., Spalton, D. J.
|
|
<strong>Dominant optic atrophy: refining the clinical diagnostic criteria in light of genetic linkage studies.</strong>
|
|
Ophthalmology 106: 123-128, 1999.
|
|
|
|
|
|
[PubMed: 9917792]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/S0161-6420(99)90013-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kim, J. Y., Hwang, J.-M., Ko, H. S., Seong, M.-W., Park, B.-J., Park, S. S.
|
|
<strong>Mitochondrial DNA content is decreased in autosomal dominant optic atrophy.</strong>
|
|
Neurology 64: 966-972, 2005.
|
|
|
|
|
|
[PubMed: 15781809]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.WNL.0000157282.76715.B1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kivlin, J. D., Lovrien, E. W., Bishop, D. T., Maumenee, I. H.
|
|
<strong>Linkage analysis in dominant optic atrophy.</strong>
|
|
Am. J. Hum. Genet. 35: 1190-1195, 1983.
|
|
|
|
|
|
[PubMed: 6580816]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kjer, P.
|
|
<strong>Infantile Optic Atrophy with Dominant Mode of Inheritance.</strong>
|
|
Copenhagen: Bogtrykkeriet Forum (pub.) 1959.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lodi, R., Tonon, C., Valentino, M. L., Iotti, S., Clementi, V., Malucelli, E., Barboni, P., Longanesi, L., Schimpf, S., Wissinger, B., Baruzzi, A., Barbiroli, B., Carelli, V.
|
|
<strong>Deficit of in vivo mitochondrial ATP production in OPA1-related dominant optic atrophy.</strong>
|
|
Ann. Neurol. 56: 719-723, 2004.
|
|
|
|
|
|
[PubMed: 15505825]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.20278]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lodi, R., Tonon, C., Valentino, M. L., Manners, D., Testa, C., Malucelli, E., La Morgia, C., Barboni, P., Carbonelli, M., Schimpf, S., Wissinger, B., Zeviani, M., Baruzzi, A., Liguori, R., Barbiroli, B., Carelli, V.
|
|
<strong>Defective mitochondrial adenosine triphosphate production in skeletal muscle from patients with dominant optic atrophy due to OPA1 mutations.</strong>
|
|
Arch. Neurol. 68: 67-73, 2011.
|
|
|
|
|
|
[PubMed: 20837821]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archneurol.2010.228]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lunkes, A., Hartung, U., Magarino, C., Rodriguez, M., Palmero, A., Rodriguez, L., Heredero, L., Weissenbach, J., Weber, J., Auburger, G.
|
|
<strong>Refinement of the OPA1 gene locus on chromosome 3q28-q29 to a region of 2-8 cM, in one Cuban pedigree with autosomal dominant optic atrophy type Kjer. (Letter)</strong>
|
|
Am. J. Hum. Genet. 57: 968-970, 1995.
|
|
|
|
|
|
[PubMed: 7573062]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Payne, M., Yang, Z., Katz, B. J., Warner, J. E. A., Weight, C. J., Zhao, Y., Pearson, E. D., Treft, R. L., Hillman, T., Kennedy, R. J., Meire, F. M., Zhang, K.
|
|
<strong>Dominant optic atrophy, sensorineural hearing loss, ptosis, and ophthalmoplegia: a syndrome caused by a missense mutation in OPA1.</strong>
|
|
Am. J. Ophthal. 138: 749-755, 2004.
|
|
|
|
|
|
[PubMed: 15531309]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajo.2004.06.011]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rice, D. S., Williams, R. W., Davisson, M. T., Harris, B., Goldowitz, D.
|
|
<strong>A new mutant phenotype of retinal ganglion cell dysgenesis discovered in the mouse. (Abstract)</strong>
|
|
Soc. Neurosci. Abst. 19: 51, 1993.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rice, D. S., Williams, R. W., Ward-Bailey, P., Johnson, K. R., Harris, B. S., Davisson, M. T., Goldowitz, D.
|
|
<strong>Mapping the Bst mutation on mouse chromosome 16: a model for human optic atrophy.</strong>
|
|
Mammalian Genome 6: 546-548, 1995.
|
|
|
|
|
|
[PubMed: 8589526]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00356174]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Seller, M. J., Behnam, J. T., Lewis, C. M., Johnston, R. L., Burdon, M. A., Spalton, D. J.
|
|
<strong>Linkage studies in dominant optic atrophy, Kjer type: possible evidence for heterogeneity.</strong>
|
|
J. Med. Genet. 34: 967-972, 1997.
|
|
|
|
|
|
[PubMed: 9429135]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.34.12.967]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Smith, D. P.
|
|
<strong>Diagnostic criteria in dominantly inherited juvenile optic atrophy: report of three new families.</strong>
|
|
Am. J. Optom. Arch. Am. Acad. Optom. 49: 183-200, 1972.
|
|
|
|
|
|
[PubMed: 4502353]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/00006324-197203000-00001]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Smith, R. S., John, S. W. M., Zabeleta, A., Davisson, M. T., Hawes, N. L., Chang, B.
|
|
<strong>The Bst locus on mouse chromosome 16 is associated with age-related subretinal neovascularization.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 2191-2195, 2000.
|
|
|
|
|
|
[PubMed: 10681427]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.040531597]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Snell, S.
|
|
<strong>Diseases of the optic nerve. I. Hereditary or congenital optic atrophy and allied cases.</strong>
|
|
Trans. Ophthal. Soc. U.K. 17: 66-81, 1897.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stendahl-Brodin, L., Moller, E., Link, H.
|
|
<strong>Hereditary optic atrophy with probable association with a specific HLA haplotype.</strong>
|
|
J. Neurol. Sci. 38: 11-21, 1978.
|
|
|
|
|
|
[PubMed: 151734]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0022-510x(78)90241-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Votruba, M., Fitzke, F. W., Holder, G. E., Carter, A., Bhattacharya, S. S., Moore, A. T.
|
|
<strong>Clinical features in affected individuals from 21 pedigrees with dominant optic atrophy.</strong>
|
|
Arch. Ophthal. 116: 351-358, 1998.
|
|
|
|
|
|
[PubMed: 9514489]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archopht.116.3.351]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Votruba, M., Moore, A. T., Bhattacharya, S. S.
|
|
<strong>Genetic refinement of dominant optic atrophy (OPA1) locus to within a 2 cM interval of chromosome 3q.</strong>
|
|
J. Med. Genet. 34: 117-121, 1997.
|
|
|
|
|
|
[PubMed: 9039986]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.34.2.117]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Votruba, M., Moore, A. T., Bhattacharya, S. S.
|
|
<strong>Demonstration of a founder effect and fine mapping of dominant optic atrophy locus on 3q28-qter by linkage disequilibrium method: a study of 38 British Isles pedigrees.</strong>
|
|
Hum. Genet. 102: 79-86, 1998.
|
|
|
|
|
|
[PubMed: 9490303]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390050657]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Votruba, M., Payne, A., Moore, A. T., Bhattacharya, S. S.
|
|
<strong>Dominant optic atrophy: exclusion and fine genetic mapping of the candidate gene, HRY.</strong>
|
|
Mammalian Genome 9: 784-787, 1998.
|
|
|
|
|
|
[PubMed: 9745030]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s003359900867]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yu-Wai-Man, P., Griffiths, P. G., Burke, A., Sellar, P. W., Clarke, M. P., Gnanaraj, L., Ah-Kine, D., Hudson, G., Czermin, B., Taylor, R. W., Horvath, R., Chinnery, P. F.
|
|
<strong>The prevalence and natural history of dominant optic atrophy due to OPA1 mutations.</strong>
|
|
Ophthalmology 117: 1538-1546, 2010.
|
|
|
|
|
|
[PubMed: 20417570]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ophtha.2009.12.038]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yu-Wai-Man, P., Griffiths, P. G., Gorman, G. S., Lourenco, C. M., Wright, A. F., Auer-Grumbach, M., Toscano, A., Musumeci, O., Valentino, M. L., Caporali, L., Lamperti, C., Tallaksen, C. M., and 24 others.
|
|
<strong>Multi-system neurological disease is common in patients with OPA1 mutations.</strong>
|
|
Brain 133: 771-786, 2010.
|
|
|
|
|
|
[PubMed: 20157015]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/awq007]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yu-Wai-Man, P., Griffiths, P. G., Hudson, G., Chinnery, P. F.
|
|
<strong>Inherited mitochondrial optic neuropathies.</strong>
|
|
J. Med. Genet. 46: 145-158, 2009. Note: Erratum: J. Med. Genet. 48: 284 only, 2011.
|
|
|
|
|
|
[PubMed: 19001017]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2007.054270]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yu-Wai-Man, P., Sitarz, K. S., Samuels, D. C., Griffiths, P. G., Reeve, A. K., Bindoff, L. A., Horvath, R., Chinnery, P. F.
|
|
<strong>OPA1 mutations cause cytochrome c oxidase deficiency due to loss of wild-type mtDNA molecules.</strong>
|
|
Hum. Molec. Genet. 19: 3043-3052, 2010.
|
|
|
|
|
|
[PubMed: 20484224]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddq209]
|
|
|
|
|
|
</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">
|
|
Marla J. F. O'Neill - updated : 10/24/2023<br>George E. Tiller - updated : 8/27/2013<br>George E. Tiller - updated : 8/16/2013<br>Jane Kelly - updated : 2/20/2012<br>Jane Kelly - updated : 2/16/2012<br>Cassandra L. Kniffin - updated : 5/19/2011<br>Cassandra L. Kniffin - updated : 6/1/2009<br>Cassandra L. Kniffin - updated : 2/5/2009<br>Jane Kelly - updated : 10/30/2007<br>Marla J. F. O'Neill - updated : 1/19/2007<br>Cassandra L. Kniffin - updated : 3/3/2006<br>Marla J. F. O'Neill - updated : 10/25/2005<br>Cassandra L. Kniffin - updated : 6/29/2005<br>Jane Kelly - updated : 6/23/2005<br>Cassandra L. Kniffin - updated : 4/28/2005<br>Jane Kelly - updated : 2/25/2003<br>Jane Kelly - updated : 10/11/2002<br>Victor A. McKusick - updated : 7/18/2001<br>Victor A. McKusick - updated : 3/16/2000<br>Victor A. McKusick - updated : 6/3/1999<br>Victor A. McKusick - updated : 10/5/1998<br>Ada Hamosh - updated : 5/13/1998<br>Victor A. McKusick - updated : 4/30/1998<br>Victor A. McKusick - updated : 3/25/1997<br>Victor A. McKusick - updated : 3/6/1997
|
|
</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">
|
|
Victor A. McKusick : 6/2/1986
|
|
</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 : 04/11/2024<br>carol : 11/21/2023<br>carol : 11/20/2023<br>carol : 10/24/2023<br>alopez : 05/11/2022<br>carol : 09/03/2020<br>ckniffin : 08/19/2020<br>carol : 08/14/2020<br>carol : 08/13/2020<br>ckniffin : 08/10/2020<br>carol : 07/16/2018<br>carol : 07/13/2018<br>carol : 12/12/2017<br>carol : 11/09/2017<br>alopez : 11/08/2017<br>ckniffin : 11/07/2017<br>carol : 01/20/2017<br>ckniffin : 01/17/2017<br>carol : 11/20/2015<br>ckniffin : 11/18/2015<br>alopez : 4/2/2015<br>mcolton : 4/1/2015<br>ckniffin : 3/31/2015<br>carol : 8/28/2014<br>carol : 4/11/2014<br>alopez : 8/28/2013<br>tpirozzi : 8/28/2013<br>tpirozzi : 8/27/2013<br>carol : 8/19/2013<br>tpirozzi : 8/19/2013<br>tpirozzi : 8/19/2013<br>tpirozzi : 8/16/2013<br>tpirozzi : 8/16/2013<br>tpirozzi : 8/16/2013<br>tpirozzi : 8/16/2013<br>tpirozzi : 8/16/2013<br>carol : 4/1/2013<br>terry : 12/20/2012<br>terry : 10/10/2012<br>alopez : 2/20/2012<br>alopez : 2/16/2012<br>wwang : 6/20/2011<br>ckniffin : 5/19/2011<br>wwang : 2/3/2011<br>alopez : 8/31/2009<br>wwang : 6/9/2009<br>ckniffin : 6/1/2009<br>wwang : 4/1/2009<br>ckniffin : 3/26/2009<br>alopez : 2/23/2009<br>wwang : 2/17/2009<br>ckniffin : 2/5/2009<br>carol : 10/30/2007<br>carol : 1/23/2007<br>carol : 1/22/2007<br>terry : 1/19/2007<br>carol : 3/10/2006<br>carol : 3/10/2006<br>ckniffin : 3/9/2006<br>ckniffin : 3/9/2006<br>ckniffin : 3/3/2006<br>alopez : 12/9/2005<br>carol : 10/25/2005<br>wwang : 7/14/2005<br>wwang : 7/13/2005<br>ckniffin : 6/29/2005<br>alopez : 6/23/2005<br>wwang : 5/10/2005<br>ckniffin : 4/28/2005<br>carol : 2/25/2003<br>carol : 2/25/2003<br>cwells : 10/11/2002<br>carol : 1/2/2002<br>mcapotos : 8/8/2001<br>terry : 7/18/2001<br>carol : 11/17/2000<br>alopez : 9/28/2000<br>alopez : 9/26/2000<br>alopez : 9/26/2000<br>alopez : 9/26/2000<br>mcapotos : 4/12/2000<br>terry : 3/16/2000<br>jlewis : 6/9/1999<br>terry : 6/3/1999<br>carol : 10/7/1998<br>terry : 10/5/1998<br>alopez : 5/13/1998<br>carol : 5/11/1998<br>carol : 5/5/1998<br>terry : 4/30/1998<br>alopez : 3/25/1997<br>alopez : 3/25/1997<br>alopez : 3/25/1997<br>terry : 3/17/1997<br>mark : 3/6/1997<br>terry : 3/4/1997<br>mark : 1/20/1996<br>mark : 1/19/1996<br>terry : 10/20/1995<br>mark : 10/2/1995<br>mimadm : 12/2/1994<br>jason : 7/25/1994<br>carol : 10/19/1992<br>supermim : 3/16/1992
|
|
</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 15, 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>
|
|
|
|
|