publicdata/nih-gov
1
0
Fork 0
Code Issues Pull requests Projects Releases Packages Wiki Activity Actions
nih-gov/www.ncbi.nlm.nih.gov/omim/301054

2871 lines
225 KiB
Text
Raw Permalink Blame History

<!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
- #301054 - VEXAS SYNDROME; VEXAS
- 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=301054"><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">#301054</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/301054"><strong>Clinical Synopsis</strong></a>
</li>
<li role="presentation">
<a href="#text"><strong>Text</strong></a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#description">Description</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#clinicalFeatures">Clinical Features</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#clinicalManagement">Clinical Management</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</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="#animalModel">Animal Model</a>
</li>
<li role="presentation">
<a href="#references"><strong>References</strong></a>
</li>
<li role="presentation">
<a href="#contributors"><strong>Contributors</strong></a>
</li>
<li role="presentation">
<a href="#creationDate"><strong>Creation Date</strong></a>
</li>
<li role="presentation">
<a href="#editHistory"><strong>Edit History</strong></a>
</li>
</ul>
</nav>
</div>
</div>
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
<div id="mimFloatingLinksMenu">
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
<h4 class="panel-title">
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
<div style="display: table-row">
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">&#9660;</div>
&nbsp;
<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;">&#9660;</div>
&nbsp;
<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=(VEXAS SYNDROME) OR (UBA1)" 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=29783&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://medlineplus.gov/genetics/condition/vexas-syndrome" 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=301054[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=596753" 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;">&#9658;</div>
&nbsp;
<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:0080828" 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/301054" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
<div><a href="https://wormbase.org/resources/disease/DOID:0080828" 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.">
&nbsp;
</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> 1290093003<br />
<strong>ORPHA:</strong> 596753<br />
<strong>DO:</strong> 0080828<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>
301054
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
VEXAS SYNDROME; VEXAS
</span>
</h3>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/X/212?start=-3&limit=10&highlight=212">
Xp11.3
</a>
</span>
</td>
<td>
<span class="mim-font">
VEXAS syndrome, somatic
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/301054"> 301054 </a>
</span>
</td>
<td>
<span class="mim-font">
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
UBA1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/314370"> 314370 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/301054" 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>
&nbsp;
<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/301054" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/301054" 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">
- Somatic mosaicism <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5848753&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5848753</a>, <a href="https://bioportal.bioontology.org/search?q=C1866227&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866227</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001442" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001442</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001442" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001442</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> Ears </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Chondritis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/363173007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">363173007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1285334&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1285334</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100662" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100662</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100662" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100662</a>]</span><br /> -
Hearing loss, sensorineural (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/60700002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">60700002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H90.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H90.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/389.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/389.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018784&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018784</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000407" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000407</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000407" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000407</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Ocular inflammation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4020969&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4020969</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100533" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100533</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100533" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100533</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Nose </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Chondritis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/363173007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">363173007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1285334&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1285334</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100662" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100662</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100662" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100662</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CARDIOVASCULAR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Vascular </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Vasculitis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/31996006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">31996006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042384&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042384</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002633" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002633</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002633" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002633</a>]</span><br /> -
Arteritis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/52089001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">52089001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I77.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I77.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/447.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">447.6</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0003860&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0003860</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012089" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012089</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012089" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012089</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> RESPIRATORY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Airways </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Airway chondritis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5435756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5435756</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Lung </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Pulmonary inflammation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/233604007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">233604007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/205237003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">205237003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714636&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714636</a>, <a href="https://bioportal.bioontology.org/search?q=C0032285&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0032285</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002090" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002090</a>]</span><br /> -
Pulmonary infiltrates <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R91.8" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R91.8</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0235896&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235896</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002113" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002113</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002113" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002113</a>]</span><br /> -
Pleural pathology <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5435757&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5435757</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKIN, NAILS, & HAIR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Skin </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Dermatitis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/703938007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">703938007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L30.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L30.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011603&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011603</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011123" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011123</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011123" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011123</a>]</span><br /> -
Neutrophilic dermatosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/724834006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">724834006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1142272&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1142272</a>]</span><br /> -
Nodules <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/27925004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">27925004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/279365004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">279365004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0028259&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028259</a>, <a href="https://bioportal.bioontology.org/search?q=C0228505&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0228505</a>]</span><br /> -
Plaques <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1522000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1522000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/38551001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">38551001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0333463&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0333463</a>, <a href="https://bioportal.bioontology.org/search?q=C0332461&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0332461</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100256</a>]</span><br /> -
Swelling <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20741006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20741006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/65124004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">65124004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/442672001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">442672001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/79654002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">79654002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/413269001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">413269001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267038008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267038008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R60.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R60.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/782.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">782.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038999&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038999</a>, <a href="https://bioportal.bioontology.org/search?q=C0013604&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013604</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000969" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000969</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MUSCLE, SOFT TISSUES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Arthralgia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/57676002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">57676002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M25.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M25.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/719.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">719.40</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/719.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">719.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0003862&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0003862</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002829</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002829</a>]</span><br /> -
Arthritis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/3723001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">3723001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M19.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M19.90</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0003864&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0003864</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001369" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001369</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001369" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001369</a>]</span><br /> -
Fatigue <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248274002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248274002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/84229001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">84229001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R53.83" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R53.83</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015672&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015672</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012378" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012378</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012378" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012378</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> METABOLIC FEATURES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Fever, recurrent <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/A68" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">A68</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714772&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714772</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001954" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001954</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/386661006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">386661006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/50177009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">50177009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/780.60" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">780.60</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001945" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001945</a>]</span><br /> -
Night sweats <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/42984000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">42984000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R61" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R61</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0028081&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028081</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030166" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030166</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030166" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030166</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEMATOLOGY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Macrocytic anemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/83414005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">83414005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0002886&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0002886</a>, <a href="https://bioportal.bioontology.org/search?q=C1420653&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1420653</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001972" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001972</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001972" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001972</a>]</span><br /> -
Thrombocytopenia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/415116008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">415116008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302215000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302215000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D69.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D69.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/287.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">287.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0392386&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0392386</a>, <a href="https://bioportal.bioontology.org/search?q=C0040034&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040034</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001873" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001873</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001873" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001873</a>]</span><br /> -
Deep vein thrombosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/404223003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">404223003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/128053003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">128053003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I82.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I82.40</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0149871&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0149871</a>, <a href="https://bioportal.bioontology.org/search?q=C0340708&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0340708</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002625" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002625</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002625" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002625</a>]</span><br /> -
Megakaryocyte dysplasia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4540467&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4540467</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031689" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031689</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031689" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031689</a>]</span><br /> -
Erythroid dysplasia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2987488&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2987488</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031688" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031688</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0031688" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0031688</a>]</span><br /> -
Myeloid dysplasia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/109995007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">109995007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405717004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405717004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/128623006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">128623006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D46" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D46</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/D46.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D46.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/238.75" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">238.75</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3463824&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3463824</a>, <a href="https://bioportal.bioontology.org/search?q=C1320638&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1320638</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002863" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002863</a>]</span><br /> -
Myelodysplastic syndrome <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/109995007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">109995007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/128623006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">128623006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D46" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D46</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/D46.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D46.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/238.75" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">238.75</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3463824&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3463824</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002863" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002863</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002863" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002863</a>]</span><br /> -
Monoclonal gammopathy of undetermined significance (MGUS) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/277577000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">277577000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/35601003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">35601003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/58648008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">58648008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D47.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D47.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026470&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026470</a>]</span><br /> -
Plasma cell dyscrasia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/415111003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">415111003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/127580003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">127580003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1959632&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1959632</a>, <a href="https://bioportal.bioontology.org/search?q=C1136084&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1136084</a>]</span><br /> -
Vacuoles in the bone marrow <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5435755&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5435755</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> IMMUNOLOGY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autoinflammation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4227884&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4227884</a>]</span><br /> -
Autoantibodies <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/314067002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">314067002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/30621004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">30621004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0004358&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0004358</a>, <a href="https://bioportal.bioontology.org/search?q=C1272321&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1272321</a>]</span><br /> -
Decreased lymphocytes <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/48813009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">48813009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D72.810" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D72.810</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/288.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">288.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0853986&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0853986</a>, <a href="https://bioportal.bioontology.org/search?q=C0024312&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0024312</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001888" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001888</a>]</span><br /> -
Myeloid degeneration <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5435754&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5435754</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Increased acute phase reactants <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4693009&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4693009</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Adult-onset (range 40 to 80 years)<br /> -
Only males are affected<br /> -
Variable manifestations<br /> -
Death from complications of the disease may occur<br /> -
Somatic mosaic mutation<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 somatic mutation in the ubiquitin-like modifier-activating enzyme 1 gene (UBA1, <a href="/entry/314370#0004">314370.0004</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;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">&#9660;</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 &lt;span class='glyphicon glyphicon-plus-sign'&gt;&lt;/span&gt at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
<strong>TEXT</strong>
</span>
</span>
</h4>
<div id="mimTextFold" class="collapse in ">
<span class="mim-text-font">
<p>A number sign (#) is used with this entry because of evidence that VEXAS syndrome (VEXAS) is caused by somatic mutation in the UBA1 gene (<a href="/entry/314370">314370</a>) on chromosome Xp11.</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">&#9660;</span>
<span class="mim-font">
<strong>Description</strong>
</span>
</h4>
</div>
<div id="mimDescriptionFold" class="collapse in ">
<span class="mim-text-font">
<p>VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome) is an adult-onset inflammatory disease that primarily affects males and is caused by somatic, not germline, mutations. The disorder is characterized by adult onset of rheumatologic symptoms at a mean age of 64 years. Features include recurrent fevers, pulmonary and dermatologic inflammatory manifestations, vasculitis, deep vein thrombosis, arthralgias, and ear and nose chondritis. Laboratory studies indicate hematologic abnormalities, including macrocytic anemia, as well as increased levels of acute-phase reactants; about half of patients have positive autoantibodies. Bone marrow biopsy shows degenerative vacuolization restricted to myeloid and erythroid precursor cells, as well as variable hematopoietic dyspoiesis and dysplasias. The condition does not respond to rheumatologic medications and the features may result in premature death (summary by <a href="#3" class="mim-tip-reference" title="Beck, D. B., Ferrada, M. A., Sikora, K. A., Ombrello, A. K., Collins, J. C., Pei, W., Balanda, N., Ross, D. L., Cardona, D. O., Wu, Z., Patel, B., Manthiram, K., and 49 others. &lt;strong&gt;Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease.&lt;/strong&gt; New Eng. J. Med. 383: 2628-2638, 2020.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/33108101/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;33108101&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=33108101[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMoa2026834&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="33108101">Beck et al., 2020</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33108101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="clinicalFeatures" class="mim-anchor"></a>
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</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>Using a genotype-driven approach, <a href="#3" class="mim-tip-reference" title="Beck, D. B., Ferrada, M. A., Sikora, K. A., Ombrello, A. K., Collins, J. C., Pei, W., Balanda, N., Ross, D. L., Cardona, D. O., Wu, Z., Patel, B., Manthiram, K., and 49 others. &lt;strong&gt;Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease.&lt;/strong&gt; New Eng. J. Med. 383: 2628-2638, 2020.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/33108101/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;33108101&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=33108101[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMoa2026834&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="33108101">Beck et al. (2020)</a> identified an adult-onset inflammatory disorder that exclusively affects males and is associated with de novo somatic mutations in the UBA1 gene. The authors reported 25 unrelated men, all above 45 years of age, who had UBA1 mutations and were diagnosed with 'VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome.' The patients were ascertained from several large cohorts of over 2,500 patients with undiagnosed or unclassified inflammatory or systemic disorders who underwent genetic investigation. The men had onset of variable inflammatory symptoms between 45 and 80 years of age. Ten patients (40%) died between 61 and 84 years of age. The majority of patients had recurrent fevers, pulmonary involvement with infiltrates and alveolitis, dermatologic manifestations, including neutrophilic dermatosis and cutaneous vasculitis, and ear and nose chondritis. More variable features included arthralgia, deep vein thrombosis, eye inflammation, and sensorineural hearing loss. Laboratory studies showed progressive hematologic abnormalities, including macrocytic anemia and thrombocytopenia, as well as increased levels of acute-phase reactants, such as CRP (<a href="/entry/123260">123260</a>) and erythrocyte sedimentation rate (ESR). Bone marrow biopsy showed degenerative vacuolization restricted to myeloid and erythroid precursor cells, as well as hematopoietic dyspoiesis. Electron microscopic studies indicated that myeloid cells were undergoing apoptosis and degeneration. Several patients had clinical diagnoses of relapsing polychondritis, Sweet syndrome (see <a href="/entry/608068">608068</a>), myelodysplasia, plasma cell dyscrasia or monoclonal gammopathy of undetermined significance, myelodysplastic syndrome, and/or polyarteritis nodosa. However, none developed an overt hematologic malignant condition. The condition showed no response to rheumatologic drugs, but glucocorticoids offered relief for severe inflammatory symptoms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33108101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Arlet, J.-B., Terrier, B., Kosmider, O. &lt;strong&gt;Mutant UBA1 and severe adult-onset autoinflammatory disease. (Letter)&lt;/strong&gt; New Eng. J. Med. 384: 2163 only, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/34077651/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;34077651&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMc2102124&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="34077651">Arlet et al. (2021)</a> reported 2 unrelated women who developed classic features of VEXAS at 87 and 78 years of age, respectively. Genetic analysis showed that both patients carried heterozygous M41V (<a href="/entry/314370#0004">314370.0004</a>) and M41L (<a href="/entry/314370#0006">314370.0006</a>) mutations in the UBA1 gene. However, both patients had acquired X chromosome monosomy in the bone marrow, resulting in expression of the mutant allele and disease manifestations. <a href="#8" class="mim-tip-reference" title="Luzzatto, L., Risitano, A. M., Notaro, R. &lt;strong&gt;Mutant UBA1 and severe adult-onset autoinflammatory disease. (Letter)&lt;/strong&gt; New Eng. J. Med. 384: 2164 only, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/34077653/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;34077653&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMc2102124&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="34077653">Luzzatto et al. (2021)</a> noted that UBA1 escapes X-inactivation, such that expression of a heterozygous mutant allele in females would likely behave as a recessive allele, and thus not cause disease manifestations in women. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=34077653+34077651" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Poulter, J. A., Collins, J. C., Cargo, C., De Tute, R. M., Evans, P., Cardona, D. O., Bowen, D. T., Cunnington, J. R., Baguley, E., Quinn, M., Green, M., McGonagle, D., Beck, D. B., Werner, A., Savic, S. &lt;strong&gt;Novel somatic mutations in UBA1 as a cause of VEXAS syndrome. (Letter)&lt;/strong&gt; Blood 137: 3676-3681, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/33690815/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;33690815&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1182/blood.2020010286&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="33690815">Poulter et al. (2021)</a> reported 10 unrelated men with VEXAS. Bone marrow histopathology in 8 of the patients who had somatic mutations at the M41 residue of the UBA1 gene demonstrated vacuolated promyelocytes, increased cellularity and granulopoiesis, and decreased erythropoiesis. Patient 9, who had a somatic S56P mutation (<a href="/entry/314370#0007">314370.0007</a>) in the UBA1 gene, had increased cellularity in bone marrow but also increased erythropoiesis and decreased granulopoiesis. Other features in this patient cohort included fever and macrocytic anemia in all 10, skin involvement in 9, pulmonary infiltrates in 2, and ear/nose chondritis in 4. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33690815" 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="Lytle, A., Bagg, A. &lt;strong&gt;VEXAS: a vivid new syndrome associated with vacuoles in various hematopoietic cells.&lt;/strong&gt; Blood 137: 3690 only, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/34196684/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;34196684&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1182/blood.2021010714&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="34196684">Lytle and Bagg (2021)</a> reported a patient with VEXAS syndrome who had an M41 mutation in the UBA1 gene and a history of macrocytic anemia, myeloma, pancytopenia, and relapsing polychondritis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34196684" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="van der Made, C. I., Potjewijd, J., Hoogstins, A., Willems, H. P. J., Kwakernaak, A. J., de Sevaux, R. G. L., van Daele, P. L. A., Simons, A., Heijstek, M., Beck, D. B., Netea, M. G., van Paassen, P., Elizabeth Hak, A., van der Veken, L. T., van Gijn, M. E., Hoischen, A., van de Veerdonk, F. L., Leavis, H. L., Rutgers, A. &lt;strong&gt;Adult-onset autoinflammation caused by somatic mutations in UBA1: a Dutch case series of patients with VEXAS.&lt;/strong&gt; J. Allergy Clin. Immun. 149: 432-439, 2022.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/34048852/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;34048852&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.jaci.2021.05.014&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="34048852">Van der Made et al. (2022)</a> identified 12 patients with VEXAS syndrome. Mean age of onset of autoinflammation characterized by constitutional symptoms and multiorgan involvement was 67 years (range, 47-79 years). Involvement included bone marrow in 12/12 patients, skin in 10/12, lungs in 8/12, lymph nodes in 7/12, heart and vasculature in 6/12, cartilage in 6/12, joints in 4/12, nervous system in 4/12, urogenital tract in 4/12, gastrointestinal tract in 3/12, eyes in 3/12, and kidneys in 2/12. The patients presented with elevated inflammatory parameters and macrocytic anemia (one patient developed macrocytosis later). Initial presentations included chondritis of the ear or nose, oligoarthritis, and pulmonary or systemic vasculitis. Histopathologic evaluation of the bone marrow showed hypercellularity and signs of bone marrow dysplasia with vacuoles in the myeloid progenitor cells in most patients. Novel findings included interstitial nephritis (1 patient), cardiac involvement (4 patients), stroke (3 patients), and intestinal perforation (2 patients) related to treatment with tocilizumab. Most patients became refractory to treatment and the mortality rate was 50%. The authors suggested that allogenic stem cell transplantation be considered at an early stage to prevent progression of organ damage. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34048852" 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="clinicalManagement" class="mim-anchor"></a>
<h4 href="#mimClinicalManagementFold" id="mimClinicalManagementToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimClinicalManagementToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Clinical Management</strong>
</span>
</h4>
</div>
<div id="mimClinicalManagementFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#5" class="mim-tip-reference" title="Diarra, A., Duployez, N., Terriou, L. &lt;strong&gt;Mutant UBA1 and severe adult-onset autoinflammatory disease. (Letter)&lt;/strong&gt; New Eng. J. Med. 384: 2163-2164, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/34077652/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;34077652&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMc2102124&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="34077652">Diarra et al. (2021)</a> and <a href="#4" class="mim-tip-reference" title="Beck, D. B., Grayson, P. C., Kastner, D. L. &lt;strong&gt;Mutant UBA1 and severe adult-onset autoinflammatory disease. Author&#x27;s reply. (Letter)&lt;/strong&gt; New Eng. J. Med. 384: 2164-2165, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/34077654/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;34077654&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMc2102124&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="34077654">Beck et al. (2021)</a> both reported successful treatment of patients with VEXAS by hematopoietic stem cell transplantation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=34077652+34077654" 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 multicenter international retrospective study of 30 VEXAS patients treated with JAK inhibitors, <a href="#7" class="mim-tip-reference" title="Heiblig, M., Ferrada, M. A., Koster, M. J., Barba, T., Gerfaud-Valentin, M., Mekinian, A., Coelho, H., Fossard, G., Barraco, F., Galicier, L., Bienvenu, B., Hirsch, P., and 13 others. &lt;strong&gt;Ruxolitinib is more effective than other JAK inhibitors to treat VEXAS syndrome: a retrospective multicenter study.&lt;/strong&gt; Blood 140: 927-931, 2022. Note: Erratum: Blood 141: 1647 only, 2023.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/35609174/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;35609174&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1182/blood.2022016642&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="35609174">Heiblig et al. (2022)</a> found that all 12 of those taking ruxolitinib showed a higher clinical response rate after 1 and 6 months of treatment compared to those treated with other JAK inhibitors. JAK inhibitor treatment was discontinued in 9 patients within 3 months after receiving other JAK inhibitors because of lack of efficacy. Of note, the data suggested that ruxolitinib has mainly a suspensive effect on disease progression and cannot cure VEXAS patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35609174" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="genotypePhenotypeCorrelations" class="mim-anchor"></a>
<h4 href="#mimGenotypePhenotypeCorrelationsFold" id="mimGenotypePhenotypeCorrelationsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimGenotypePhenotypeCorrelationsToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Genotype/Phenotype Correlations</strong>
</span>
</h4>
</div>
<div id="mimGenotypePhenotypeCorrelationsFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#6" class="mim-tip-reference" title="Ferrada, M. A., Savic, S., Cardona, D. O., Collins, J. C., Alessi, H., Gutierrez-Rodrigues, F., Kumar, D. B. U., Wilson, L., Goodspeed, W., Topilow, J. S., Paik, J. J., Poulter, J. A., and 20 others. &lt;strong&gt;Translation of cytoplasmic UBA1 contributes to VEXAS syndrome pathogenesis.&lt;/strong&gt; Blood 140: 1496-1506, 2022.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/35793467/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;35793467&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1182/blood.2022016985&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="35793467">Ferrada et al. (2022)</a> analyzed 83 patients with VEXAS syndrome due to a somatic pathogenic variant at residue Met41 in the UBA1 gene, which is the start codon for the cytoplasmic UBA1b isoform (see M41V, <a href="/entry/314370#0004">314370.0004</a>; M41T, <a href="/entry/314370#0005">314370.0005</a>; and M41L <a href="/entry/314370#0006">314370.0006</a>). All patients were male and Caucasian with a median age at symptom onset of 66 years. Clinical features were characteristic for the disease, but there were some differences associated with the specific variants. Those with M41V were more likely to have an undifferentiated inflammatory syndrome and showed decreased survival compared to those with M41T or M41L. Patients with M41V were less likely to develop ear chondritis, which was associated with overall better survival in the cohort. Patients with M41T had more inflammatory eye disease compared to the others. Decreased survival was also observed in those who were transfusion-dependent. Detailed in vitro studies of the mutations in HEK293 cells and in patient peripheral mononuclear cells demonstrated that all the mutations resulted in decreased levels of UBA1b, with the largest decrease in cells carrying the M41V mutation (about 2-fold lower than M41L or M41T). These findings indicated that M41V supports less translation of UBA1b than the other variants, and showed that VEXAS syndrome severity inversely correlates with residual UBA1b levels. The authors concluded that there is a certain minimal threshold of cellular UBA1b levels required to initiate disease progression, and that the major cause of disease is loss of UBA1b or its activity, rather than gain of UBA1c. This regulation of residual UBA1b translation thus appears to be fundamental to the pathogenesis of VEXAS syndrome and affects disease prognosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35793467" 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">&#9660;</span>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>In 25 unrelated men with VEXAS syndrome, <a href="#3" class="mim-tip-reference" title="Beck, D. B., Ferrada, M. A., Sikora, K. A., Ombrello, A. K., Collins, J. C., Pei, W., Balanda, N., Ross, D. L., Cardona, D. O., Wu, Z., Patel, B., Manthiram, K., and 49 others. &lt;strong&gt;Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease.&lt;/strong&gt; New Eng. J. Med. 383: 2628-2638, 2020.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/33108101/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;33108101&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=33108101[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMoa2026834&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="33108101">Beck et al. (2020)</a> identified 1 of 3 somatic mutations affecting codon Met41 in the UBA1 gene (M41V, <a href="/entry/314370#0004">314370.0004</a>; M41T, <a href="/entry/314370#0005">314370.0005</a>; and M41L, <a href="/entry/314370#0006">314370.0006</a>), which is the translation initiation site for the cytoplasmic UBA1b isoform. The mutations, which were found by exome or targeted sequencing and confirmed by Sanger sequencing, were absent from public databases, including gnomAD. None had a family history of a similar disorder. All affected men were somatic mosaic for the UBA1 mutation, which was present in peripheral myeloid cells, granulocytes, and monocytes, but not in fibroblasts or mature lymphoid cells. In contrast, bone marrow examination showed that the UBA1 mutations were present in hematopoietic stem cells and in multipotent early marrow progenitor cells. However, patients also had decreased peripheral lymphocyte counts, suggesting that mutant lymphocytes either did not proliferate or did not survive. UBA1 is normally expressed as 2 isoforms differing at the translation site: nuclear UBA1a (initiation at Met1) and cytoplasmic UBA1b (initiation at Met41). In vitro expression of the Met41 mutations into HEK293T cells resulted in loss of UBA1b and the presence of a shorter abnormal isoform, designated UBA1c, that was initiated from a downstream Met67 initiation codon. UBA1c localized to the cytoplasm, but was catalytically impaired compared to UBA1a and UBA1b. The findings suggested that the mutations identified in patients with VEXAS syndrome favored the production of functionally defective cytoplasmic UBA1 isoform. Mutant monocytes derived from the patients showed loss of ubiquitylation, which caused upregulation of the stress and unfolded protein responses, as well as dysregulation of autophagy. These findings suggested that the inflammation observed was mainly due to mutant myeloid cells, although there was also evidence of disrupted B and T cell and neutrophil activation. Transcriptome analysis of patient peripheral blood cells showed a gene expression pattern consistent with the activation of multiple innate immune pathways, including TNF (<a href="/entry/191160">191160</a>), IL6 (<a href="/entry/147620">147620</a>), and IFNG (<a href="/entry/147570">147570</a>). <a href="#3" class="mim-tip-reference" title="Beck, D. B., Ferrada, M. A., Sikora, K. A., Ombrello, A. K., Collins, J. C., Pei, W., Balanda, N., Ross, D. L., Cardona, D. O., Wu, Z., Patel, B., Manthiram, K., and 49 others. &lt;strong&gt;Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease.&lt;/strong&gt; New Eng. J. Med. 383: 2628-2638, 2020.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/33108101/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;33108101&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=33108101[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMoa2026834&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="33108101">Beck et al. (2020)</a> noted that many patients had myelodysplasia in addition to systemic inflammation and rheumatologic manifestations; they concluded that subcellular ubiquitin regulation and activation play an important role during hematopoiesis and regulation of the immune response. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33108101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Poulter, J. A., Collins, J. C., Cargo, C., De Tute, R. M., Evans, P., Cardona, D. O., Bowen, D. T., Cunnington, J. R., Baguley, E., Quinn, M., Green, M., McGonagle, D., Beck, D. B., Werner, A., Savic, S. &lt;strong&gt;Novel somatic mutations in UBA1 as a cause of VEXAS syndrome. (Letter)&lt;/strong&gt; Blood 137: 3676-3681, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/33690815/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;33690815&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1182/blood.2020010286&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="33690815">Poulter et al. (2021)</a> identified somatic mutations in the UBA1 gene in 10 unrelated men with VEXAS syndrome. The mutations were identified by Sanger sequencing in peripheral blood or bone marrow from the patients. Eight patients had previously reported mutations; 3 had the M41V mutation and 5 had the M41T mutation. One patient had an S56P mutation (<a href="/entry/314370#0007">314370.0007</a>), which did not affect UBA1 cellular localization or result in isoform expression abnormalities in HEK293 cells transfected with the mutant transcript. <a href="#10" class="mim-tip-reference" title="Poulter, J. A., Collins, J. C., Cargo, C., De Tute, R. M., Evans, P., Cardona, D. O., Bowen, D. T., Cunnington, J. R., Baguley, E., Quinn, M., Green, M., McGonagle, D., Beck, D. B., Werner, A., Savic, S. &lt;strong&gt;Novel somatic mutations in UBA1 as a cause of VEXAS syndrome. (Letter)&lt;/strong&gt; Blood 137: 3676-3681, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/33690815/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;33690815&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1182/blood.2020010286&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="33690815">Poulter et al. (2021)</a> demonstrated that the S56P mutation resulted in temperature-dependent impairment of UBA1 catalytic activity. Another patient had a splice site mutation (<a href="/entry/314370#0008">314370.0008</a>), which resulted in multiple incorrectly spliced transcripts and a reduction in the correctly spliced transcript. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33690815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Among a cohort of undiagnosed patients with inborn errors of immunity from academic hospitals in the Netherlands, <a href="#11" class="mim-tip-reference" title="van der Made, C. I., Potjewijd, J., Hoogstins, A., Willems, H. P. J., Kwakernaak, A. J., de Sevaux, R. G. L., van Daele, P. L. A., Simons, A., Heijstek, M., Beck, D. B., Netea, M. G., van Paassen, P., Elizabeth Hak, A., van der Veken, L. T., van Gijn, M. E., Hoischen, A., van de Veerdonk, F. L., Leavis, H. L., Rutgers, A. &lt;strong&gt;Adult-onset autoinflammation caused by somatic mutations in UBA1: a Dutch case series of patients with VEXAS.&lt;/strong&gt; J. Allergy Clin. Immun. 149: 432-439, 2022.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/34048852/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;34048852&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.jaci.2021.05.014&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="34048852">van der Made et al. (2022)</a> performed systematic reanalysis of exome sequencing data and targeted Sanger sequencing on those without exome data and identified 12 male patients with VEXAS syndrome and somatic mutations at met41 in the UBA1 gene: 7 with M41T, 4 with M41V, and 1 with M41L. The variant allele fraction varied from 17% to 85%. The authors noted that the low level of variant allele fraction (17%) associated with VEXAS syndrome in one of their patients emphasized the importance of specifically evaluating somatic variants during exome analysis to avoid inappropriate elimination of variants if the variant allele fraction is below a certain threshold. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34048852" 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">&#9660;</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 retrospective observational study using exome data, <a href="#2" class="mim-tip-reference" title="Beck, D. B., Bodian, D. L., Shah, V., Mirshahi, U. L., Kim, J., Ding, Y., Magaziner, S. J., Strande, N. T., Cantor, A., Haley, J. S., Cook, A., Hill, W., Schwartz, A. L., Grayson, P. C., Ferrada, M. A., Kastner, D. L., Carey, D. J., Stewart, D. R. &lt;strong&gt;Estimated prevalence and clinical manifestations of UBA1 variants associated with VEXAS syndrome in a clinical population.&lt;/strong&gt; JAMA 329: 318-324, 2023.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/36692560/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;36692560&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/jama.2022.24836&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="36692560">Beck et al. (2023)</a> identified somatic UBA1 mutations in 11 individuals (9 males and 2 females) from a cohort of 163,096 participants from a health care cohort in Pennsylvania. All 11 patients had clinical manifestations of VEXAS syndrome, although 5 (45%) did not meet criteria for rheumatologic and/or hematologic diagnoses associated with the disease. However, all 11 patients had anemia, usually macrocytic, and most had thrombocytopenia; 4 (36%) had myelodysplastic syndrome (MDS). Seven (64%) had arthritis and 4 (36%) were diagnosed with various rheumatologic diseases. Skin and pulmonary involvement were common (in 73% and 91% of patients, respectively). Overall, UBA1 variants were found in 1 of 13,591 unrelated individuals, 1 of 4,269 men older than age 50, and 1 of 26,238 women older than age 50. The authors emphasized that since many individuals with VEXAS syndrome may not be identified through phenotype-based ascertainment and/or have nonspecific clinical diagnoses, testing for UBA1 mutations may be indicated in appropriate cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36692560" 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">&#9660;</span>
<span class="mim-font">
<strong>Animal Model</strong>
</span>
</h4>
</div>
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#3" class="mim-tip-reference" title="Beck, D. B., Ferrada, M. A., Sikora, K. A., Ombrello, A. K., Collins, J. C., Pei, W., Balanda, N., Ross, D. L., Cardona, D. O., Wu, Z., Patel, B., Manthiram, K., and 49 others. &lt;strong&gt;Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease.&lt;/strong&gt; New Eng. J. Med. 383: 2628-2638, 2020.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/33108101/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;33108101&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=33108101[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMoa2026834&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="33108101">Beck et al. (2020)</a> found that zebrafish with loss of uba1 had growth abnormalities and early death compared to controls. The defects were associated with upregulation of the expression of inflammatory genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33108101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
</div>
<div>
<a id="references"class="mim-anchor"></a>
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span class="mim-font">
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</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="Arlet2021" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Arlet, J.-B., Terrier, B., Kosmider, O.
<strong>Mutant UBA1 and severe adult-onset autoinflammatory disease. (Letter)</strong>
New Eng. J. Med. 384: 2163 only, 2021.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34077651/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34077651</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34077651" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJMc2102124" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="2" class="mim-anchor"></a>
<a id="Beck2023" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Beck, D. B., Bodian, D. L., Shah, V., Mirshahi, U. L., Kim, J., Ding, Y., Magaziner, S. J., Strande, N. T., Cantor, A., Haley, J. S., Cook, A., Hill, W., Schwartz, A. L., Grayson, P. C., Ferrada, M. A., Kastner, D. L., Carey, D. J., Stewart, D. R.
<strong>Estimated prevalence and clinical manifestations of UBA1 variants associated with VEXAS syndrome in a clinical population.</strong>
JAMA 329: 318-324, 2023.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36692560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36692560</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36692560" 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/jama.2022.24836" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="3" class="mim-anchor"></a>
<a id="Beck2020" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Beck, D. B., Ferrada, M. A., Sikora, K. A., Ombrello, A. K., Collins, J. C., Pei, W., Balanda, N., Ross, D. L., Cardona, D. O., Wu, Z., Patel, B., Manthiram, K., and 49 others.
<strong>Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease.</strong>
New Eng. J. Med. 383: 2628-2638, 2020.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33108101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33108101</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33108101[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=33108101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJMoa2026834" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="4" class="mim-anchor"></a>
<a id="Beck2021" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Beck, D. B., Grayson, P. C., Kastner, D. L.
<strong>Mutant UBA1 and severe adult-onset autoinflammatory disease. Author's reply. (Letter)</strong>
New Eng. J. Med. 384: 2164-2165, 2021.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34077654/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34077654</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34077654" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJMc2102124" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="5" class="mim-anchor"></a>
<a id="Diarra2021" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Diarra, A., Duployez, N., Terriou, L.
<strong>Mutant UBA1 and severe adult-onset autoinflammatory disease. (Letter)</strong>
New Eng. J. Med. 384: 2163-2164, 2021.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34077652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34077652</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34077652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJMc2102124" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="6" class="mim-anchor"></a>
<a id="Ferrada2022" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ferrada, M. A., Savic, S., Cardona, D. O., Collins, J. C., Alessi, H., Gutierrez-Rodrigues, F., Kumar, D. B. U., Wilson, L., Goodspeed, W., Topilow, J. S., Paik, J. J., Poulter, J. A., and 20 others.
<strong>Translation of cytoplasmic UBA1 contributes to VEXAS syndrome pathogenesis.</strong>
Blood 140: 1496-1506, 2022.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35793467/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35793467</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35793467" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1182/blood.2022016985" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="7" class="mim-anchor"></a>
<a id="Heiblig2022" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Heiblig, M., Ferrada, M. A., Koster, M. J., Barba, T., Gerfaud-Valentin, M., Mekinian, A., Coelho, H., Fossard, G., Barraco, F., Galicier, L., Bienvenu, B., Hirsch, P., and 13 others.
<strong>Ruxolitinib is more effective than other JAK inhibitors to treat VEXAS syndrome: a retrospective multicenter study.</strong>
Blood 140: 927-931, 2022. Note: Erratum: Blood 141: 1647 only, 2023.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35609174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35609174</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35609174" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1182/blood.2022016642" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="8" class="mim-anchor"></a>
<a id="Luzzatto2021" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Luzzatto, L., Risitano, A. M., Notaro, R.
<strong>Mutant UBA1 and severe adult-onset autoinflammatory disease. (Letter)</strong>
New Eng. J. Med. 384: 2164 only, 2021.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34077653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34077653</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34077653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJMc2102124" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="9" class="mim-anchor"></a>
<a id="Lytle2021" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lytle, A., Bagg, A.
<strong>VEXAS: a vivid new syndrome associated with vacuoles in various hematopoietic cells.</strong>
Blood 137: 3690 only, 2021.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34196684/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34196684</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34196684" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1182/blood.2021010714" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="10" class="mim-anchor"></a>
<a id="Poulter2021" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Poulter, J. A., Collins, J. C., Cargo, C., De Tute, R. M., Evans, P., Cardona, D. O., Bowen, D. T., Cunnington, J. R., Baguley, E., Quinn, M., Green, M., McGonagle, D., Beck, D. B., Werner, A., Savic, S.
<strong>Novel somatic mutations in UBA1 as a cause of VEXAS syndrome. (Letter)</strong>
Blood 137: 3676-3681, 2021.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33690815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33690815</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33690815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1182/blood.2020010286" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="11" class="mim-anchor"></a>
<a id="van der Made2022" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
van der Made, C. I., Potjewijd, J., Hoogstins, A., Willems, H. P. J., Kwakernaak, A. J., de Sevaux, R. G. L., van Daele, P. L. A., Simons, A., Heijstek, M., Beck, D. B., Netea, M. G., van Paassen, P., Elizabeth Hak, A., van der Veken, L. T., van Gijn, M. E., Hoischen, A., van de Veerdonk, F. L., Leavis, H. L., Rutgers, A.
<strong>Adult-onset autoinflammation caused by somatic mutations in UBA1: a Dutch case series of patients with VEXAS.</strong>
J. Allergy Clin. Immun. 149: 432-439, 2022.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34048852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34048852</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34048852" 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.jaci.2021.05.014" target="_blank">Full Text</a>]
</p>
</div>
</li>
</ol>
<div>
<br />
</div>
</div>
</div>
<div>
<a id="contributors" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="mim-text-font">
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Cassandra L. Kniffin - updated : 02/02/2023
</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">
Sonja A. Rasmussen - updated : 12/20/2022<br>Hilary J. Vernon - updated : 09/30/2021<br>Cassandra L. Kniffin - updated : 06/11/2021
</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">
Cassandra L. Kniffin : 11/09/2020
</span>
</div>
</div>
</div>
<div>
<a id="editHistory" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="text-nowrap mim-text-font">
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
carol : 06/08/2023
</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 : 02/08/2023<br>alopez : 02/06/2023<br>ckniffin : 02/02/2023<br>carol : 12/21/2022<br>carol : 12/20/2022<br>carol : 10/04/2021<br>carol : 10/01/2021<br>carol : 09/30/2021<br>carol : 06/23/2021<br>ckniffin : 06/11/2021<br>carol : 01/25/2021<br>carol : 11/12/2020<br>ckniffin : 11/10/2020
</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> 301054
</span>
</h3>
</div>
<div>
<h3>
<span class="mim-font">
VEXAS SYNDROME; VEXAS
</span>
</h3>
</div>
<div>
<br />
</div>
</div>
<div>
<p>
<span class="mim-text-font">
<strong>SNOMEDCT:</strong> 1290093003; &nbsp;
<strong>ORPHA:</strong> 596753; &nbsp;
<strong>DO:</strong> 0080828; &nbsp;
</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">
Xp11.3
</span>
</td>
<td>
<span class="mim-font">
VEXAS syndrome, somatic
</span>
</td>
<td>
<span class="mim-font">
301054
</span>
</td>
<td>
<span class="mim-font">
</span>
</td>
<td>
<span class="mim-font">
3
</span>
</td>
<td>
<span class="mim-font">
UBA1
</span>
</td>
<td>
<span class="mim-font">
314370
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>TEXT</strong>
</span>
</h4>
<span class="mim-text-font">
<p>A number sign (#) is used with this entry because of evidence that VEXAS syndrome (VEXAS) is caused by somatic mutation in the UBA1 gene (314370) on chromosome Xp11.</p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Description</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome) is an adult-onset inflammatory disease that primarily affects males and is caused by somatic, not germline, mutations. The disorder is characterized by adult onset of rheumatologic symptoms at a mean age of 64 years. Features include recurrent fevers, pulmonary and dermatologic inflammatory manifestations, vasculitis, deep vein thrombosis, arthralgias, and ear and nose chondritis. Laboratory studies indicate hematologic abnormalities, including macrocytic anemia, as well as increased levels of acute-phase reactants; about half of patients have positive autoantibodies. Bone marrow biopsy shows degenerative vacuolization restricted to myeloid and erythroid precursor cells, as well as variable hematopoietic dyspoiesis and dysplasias. The condition does not respond to rheumatologic medications and the features may result in premature death (summary by Beck et al., 2020). </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Clinical Features</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Using a genotype-driven approach, Beck et al. (2020) identified an adult-onset inflammatory disorder that exclusively affects males and is associated with de novo somatic mutations in the UBA1 gene. The authors reported 25 unrelated men, all above 45 years of age, who had UBA1 mutations and were diagnosed with 'VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome.' The patients were ascertained from several large cohorts of over 2,500 patients with undiagnosed or unclassified inflammatory or systemic disorders who underwent genetic investigation. The men had onset of variable inflammatory symptoms between 45 and 80 years of age. Ten patients (40%) died between 61 and 84 years of age. The majority of patients had recurrent fevers, pulmonary involvement with infiltrates and alveolitis, dermatologic manifestations, including neutrophilic dermatosis and cutaneous vasculitis, and ear and nose chondritis. More variable features included arthralgia, deep vein thrombosis, eye inflammation, and sensorineural hearing loss. Laboratory studies showed progressive hematologic abnormalities, including macrocytic anemia and thrombocytopenia, as well as increased levels of acute-phase reactants, such as CRP (123260) and erythrocyte sedimentation rate (ESR). Bone marrow biopsy showed degenerative vacuolization restricted to myeloid and erythroid precursor cells, as well as hematopoietic dyspoiesis. Electron microscopic studies indicated that myeloid cells were undergoing apoptosis and degeneration. Several patients had clinical diagnoses of relapsing polychondritis, Sweet syndrome (see 608068), myelodysplasia, plasma cell dyscrasia or monoclonal gammopathy of undetermined significance, myelodysplastic syndrome, and/or polyarteritis nodosa. However, none developed an overt hematologic malignant condition. The condition showed no response to rheumatologic drugs, but glucocorticoids offered relief for severe inflammatory symptoms. </p><p>Arlet et al. (2021) reported 2 unrelated women who developed classic features of VEXAS at 87 and 78 years of age, respectively. Genetic analysis showed that both patients carried heterozygous M41V (314370.0004) and M41L (314370.0006) mutations in the UBA1 gene. However, both patients had acquired X chromosome monosomy in the bone marrow, resulting in expression of the mutant allele and disease manifestations. Luzzatto et al. (2021) noted that UBA1 escapes X-inactivation, such that expression of a heterozygous mutant allele in females would likely behave as a recessive allele, and thus not cause disease manifestations in women. </p><p>Poulter et al. (2021) reported 10 unrelated men with VEXAS. Bone marrow histopathology in 8 of the patients who had somatic mutations at the M41 residue of the UBA1 gene demonstrated vacuolated promyelocytes, increased cellularity and granulopoiesis, and decreased erythropoiesis. Patient 9, who had a somatic S56P mutation (314370.0007) in the UBA1 gene, had increased cellularity in bone marrow but also increased erythropoiesis and decreased granulopoiesis. Other features in this patient cohort included fever and macrocytic anemia in all 10, skin involvement in 9, pulmonary infiltrates in 2, and ear/nose chondritis in 4. </p><p>Lytle and Bagg (2021) reported a patient with VEXAS syndrome who had an M41 mutation in the UBA1 gene and a history of macrocytic anemia, myeloma, pancytopenia, and relapsing polychondritis. </p><p>Van der Made et al. (2022) identified 12 patients with VEXAS syndrome. Mean age of onset of autoinflammation characterized by constitutional symptoms and multiorgan involvement was 67 years (range, 47-79 years). Involvement included bone marrow in 12/12 patients, skin in 10/12, lungs in 8/12, lymph nodes in 7/12, heart and vasculature in 6/12, cartilage in 6/12, joints in 4/12, nervous system in 4/12, urogenital tract in 4/12, gastrointestinal tract in 3/12, eyes in 3/12, and kidneys in 2/12. The patients presented with elevated inflammatory parameters and macrocytic anemia (one patient developed macrocytosis later). Initial presentations included chondritis of the ear or nose, oligoarthritis, and pulmonary or systemic vasculitis. Histopathologic evaluation of the bone marrow showed hypercellularity and signs of bone marrow dysplasia with vacuoles in the myeloid progenitor cells in most patients. Novel findings included interstitial nephritis (1 patient), cardiac involvement (4 patients), stroke (3 patients), and intestinal perforation (2 patients) related to treatment with tocilizumab. Most patients became refractory to treatment and the mortality rate was 50%. The authors suggested that allogenic stem cell transplantation be considered at an early stage to prevent progression of organ damage. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Clinical Management</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Diarra et al. (2021) and Beck et al. (2021) both reported successful treatment of patients with VEXAS by hematopoietic stem cell transplantation. </p><p>In a multicenter international retrospective study of 30 VEXAS patients treated with JAK inhibitors, Heiblig et al. (2022) found that all 12 of those taking ruxolitinib showed a higher clinical response rate after 1 and 6 months of treatment compared to those treated with other JAK inhibitors. JAK inhibitor treatment was discontinued in 9 patients within 3 months after receiving other JAK inhibitors because of lack of efficacy. Of note, the data suggested that ruxolitinib has mainly a suspensive effect on disease progression and cannot cure VEXAS patients. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Genotype/Phenotype Correlations</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Ferrada et al. (2022) analyzed 83 patients with VEXAS syndrome due to a somatic pathogenic variant at residue Met41 in the UBA1 gene, which is the start codon for the cytoplasmic UBA1b isoform (see M41V, 314370.0004; M41T, 314370.0005; and M41L 314370.0006). All patients were male and Caucasian with a median age at symptom onset of 66 years. Clinical features were characteristic for the disease, but there were some differences associated with the specific variants. Those with M41V were more likely to have an undifferentiated inflammatory syndrome and showed decreased survival compared to those with M41T or M41L. Patients with M41V were less likely to develop ear chondritis, which was associated with overall better survival in the cohort. Patients with M41T had more inflammatory eye disease compared to the others. Decreased survival was also observed in those who were transfusion-dependent. Detailed in vitro studies of the mutations in HEK293 cells and in patient peripheral mononuclear cells demonstrated that all the mutations resulted in decreased levels of UBA1b, with the largest decrease in cells carrying the M41V mutation (about 2-fold lower than M41L or M41T). These findings indicated that M41V supports less translation of UBA1b than the other variants, and showed that VEXAS syndrome severity inversely correlates with residual UBA1b levels. The authors concluded that there is a certain minimal threshold of cellular UBA1b levels required to initiate disease progression, and that the major cause of disease is loss of UBA1b or its activity, rather than gain of UBA1c. This regulation of residual UBA1b translation thus appears to be fundamental to the pathogenesis of VEXAS syndrome and affects disease prognosis. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In 25 unrelated men with VEXAS syndrome, Beck et al. (2020) identified 1 of 3 somatic mutations affecting codon Met41 in the UBA1 gene (M41V, 314370.0004; M41T, 314370.0005; and M41L, 314370.0006), which is the translation initiation site for the cytoplasmic UBA1b isoform. The mutations, which were found by exome or targeted sequencing and confirmed by Sanger sequencing, were absent from public databases, including gnomAD. None had a family history of a similar disorder. All affected men were somatic mosaic for the UBA1 mutation, which was present in peripheral myeloid cells, granulocytes, and monocytes, but not in fibroblasts or mature lymphoid cells. In contrast, bone marrow examination showed that the UBA1 mutations were present in hematopoietic stem cells and in multipotent early marrow progenitor cells. However, patients also had decreased peripheral lymphocyte counts, suggesting that mutant lymphocytes either did not proliferate or did not survive. UBA1 is normally expressed as 2 isoforms differing at the translation site: nuclear UBA1a (initiation at Met1) and cytoplasmic UBA1b (initiation at Met41). In vitro expression of the Met41 mutations into HEK293T cells resulted in loss of UBA1b and the presence of a shorter abnormal isoform, designated UBA1c, that was initiated from a downstream Met67 initiation codon. UBA1c localized to the cytoplasm, but was catalytically impaired compared to UBA1a and UBA1b. The findings suggested that the mutations identified in patients with VEXAS syndrome favored the production of functionally defective cytoplasmic UBA1 isoform. Mutant monocytes derived from the patients showed loss of ubiquitylation, which caused upregulation of the stress and unfolded protein responses, as well as dysregulation of autophagy. These findings suggested that the inflammation observed was mainly due to mutant myeloid cells, although there was also evidence of disrupted B and T cell and neutrophil activation. Transcriptome analysis of patient peripheral blood cells showed a gene expression pattern consistent with the activation of multiple innate immune pathways, including TNF (191160), IL6 (147620), and IFNG (147570). Beck et al. (2020) noted that many patients had myelodysplasia in addition to systemic inflammation and rheumatologic manifestations; they concluded that subcellular ubiquitin regulation and activation play an important role during hematopoiesis and regulation of the immune response. </p><p>Poulter et al. (2021) identified somatic mutations in the UBA1 gene in 10 unrelated men with VEXAS syndrome. The mutations were identified by Sanger sequencing in peripheral blood or bone marrow from the patients. Eight patients had previously reported mutations; 3 had the M41V mutation and 5 had the M41T mutation. One patient had an S56P mutation (314370.0007), which did not affect UBA1 cellular localization or result in isoform expression abnormalities in HEK293 cells transfected with the mutant transcript. Poulter et al. (2021) demonstrated that the S56P mutation resulted in temperature-dependent impairment of UBA1 catalytic activity. Another patient had a splice site mutation (314370.0008), which resulted in multiple incorrectly spliced transcripts and a reduction in the correctly spliced transcript. </p><p>Among a cohort of undiagnosed patients with inborn errors of immunity from academic hospitals in the Netherlands, van der Made et al. (2022) performed systematic reanalysis of exome sequencing data and targeted Sanger sequencing on those without exome data and identified 12 male patients with VEXAS syndrome and somatic mutations at met41 in the UBA1 gene: 7 with M41T, 4 with M41V, and 1 with M41L. The variant allele fraction varied from 17% to 85%. The authors noted that the low level of variant allele fraction (17%) associated with VEXAS syndrome in one of their patients emphasized the importance of specifically evaluating somatic variants during exome analysis to avoid inappropriate elimination of variants if the variant allele fraction is below a certain threshold. </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 retrospective observational study using exome data, Beck et al. (2023) identified somatic UBA1 mutations in 11 individuals (9 males and 2 females) from a cohort of 163,096 participants from a health care cohort in Pennsylvania. All 11 patients had clinical manifestations of VEXAS syndrome, although 5 (45%) did not meet criteria for rheumatologic and/or hematologic diagnoses associated with the disease. However, all 11 patients had anemia, usually macrocytic, and most had thrombocytopenia; 4 (36%) had myelodysplastic syndrome (MDS). Seven (64%) had arthritis and 4 (36%) were diagnosed with various rheumatologic diseases. Skin and pulmonary involvement were common (in 73% and 91% of patients, respectively). Overall, UBA1 variants were found in 1 of 13,591 unrelated individuals, 1 of 4,269 men older than age 50, and 1 of 26,238 women older than age 50. The authors emphasized that since many individuals with VEXAS syndrome may not be identified through phenotype-based ascertainment and/or have nonspecific clinical diagnoses, testing for UBA1 mutations may be indicated in appropriate cases. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Animal Model</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Beck et al. (2020) found that zebrafish with loss of uba1 had growth abnormalities and early death compared to controls. The defects were associated with upregulation of the expression of inflammatory genes. </p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div>
<ol>
<li>
<p class="mim-text-font">
Arlet, J.-B., Terrier, B., Kosmider, O.
<strong>Mutant UBA1 and severe adult-onset autoinflammatory disease. (Letter)</strong>
New Eng. J. Med. 384: 2163 only, 2021.
[PubMed: 34077651]
[Full Text: https://doi.org/10.1056/NEJMc2102124]
</p>
</li>
<li>
<p class="mim-text-font">
Beck, D. B., Bodian, D. L., Shah, V., Mirshahi, U. L., Kim, J., Ding, Y., Magaziner, S. J., Strande, N. T., Cantor, A., Haley, J. S., Cook, A., Hill, W., Schwartz, A. L., Grayson, P. C., Ferrada, M. A., Kastner, D. L., Carey, D. J., Stewart, D. R.
<strong>Estimated prevalence and clinical manifestations of UBA1 variants associated with VEXAS syndrome in a clinical population.</strong>
JAMA 329: 318-324, 2023.
[PubMed: 36692560]
[Full Text: https://doi.org/10.1001/jama.2022.24836]
</p>
</li>
<li>
<p class="mim-text-font">
Beck, D. B., Ferrada, M. A., Sikora, K. A., Ombrello, A. K., Collins, J. C., Pei, W., Balanda, N., Ross, D. L., Cardona, D. O., Wu, Z., Patel, B., Manthiram, K., and 49 others.
<strong>Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease.</strong>
New Eng. J. Med. 383: 2628-2638, 2020.
[PubMed: 33108101]
[Full Text: https://doi.org/10.1056/NEJMoa2026834]
</p>
</li>
<li>
<p class="mim-text-font">
Beck, D. B., Grayson, P. C., Kastner, D. L.
<strong>Mutant UBA1 and severe adult-onset autoinflammatory disease. Author&#x27;s reply. (Letter)</strong>
New Eng. J. Med. 384: 2164-2165, 2021.
[PubMed: 34077654]
[Full Text: https://doi.org/10.1056/NEJMc2102124]
</p>
</li>
<li>
<p class="mim-text-font">
Diarra, A., Duployez, N., Terriou, L.
<strong>Mutant UBA1 and severe adult-onset autoinflammatory disease. (Letter)</strong>
New Eng. J. Med. 384: 2163-2164, 2021.
[PubMed: 34077652]
[Full Text: https://doi.org/10.1056/NEJMc2102124]
</p>
</li>
<li>
<p class="mim-text-font">
Ferrada, M. A., Savic, S., Cardona, D. O., Collins, J. C., Alessi, H., Gutierrez-Rodrigues, F., Kumar, D. B. U., Wilson, L., Goodspeed, W., Topilow, J. S., Paik, J. J., Poulter, J. A., and 20 others.
<strong>Translation of cytoplasmic UBA1 contributes to VEXAS syndrome pathogenesis.</strong>
Blood 140: 1496-1506, 2022.
[PubMed: 35793467]
[Full Text: https://doi.org/10.1182/blood.2022016985]
</p>
</li>
<li>
<p class="mim-text-font">
Heiblig, M., Ferrada, M. A., Koster, M. J., Barba, T., Gerfaud-Valentin, M., Mekinian, A., Coelho, H., Fossard, G., Barraco, F., Galicier, L., Bienvenu, B., Hirsch, P., and 13 others.
<strong>Ruxolitinib is more effective than other JAK inhibitors to treat VEXAS syndrome: a retrospective multicenter study.</strong>
Blood 140: 927-931, 2022. Note: Erratum: Blood 141: 1647 only, 2023.
[PubMed: 35609174]
[Full Text: https://doi.org/10.1182/blood.2022016642]
</p>
</li>
<li>
<p class="mim-text-font">
Luzzatto, L., Risitano, A. M., Notaro, R.
<strong>Mutant UBA1 and severe adult-onset autoinflammatory disease. (Letter)</strong>
New Eng. J. Med. 384: 2164 only, 2021.
[PubMed: 34077653]
[Full Text: https://doi.org/10.1056/NEJMc2102124]
</p>
</li>
<li>
<p class="mim-text-font">
Lytle, A., Bagg, A.
<strong>VEXAS: a vivid new syndrome associated with vacuoles in various hematopoietic cells.</strong>
Blood 137: 3690 only, 2021.
[PubMed: 34196684]
[Full Text: https://doi.org/10.1182/blood.2021010714]
</p>
</li>
<li>
<p class="mim-text-font">
Poulter, J. A., Collins, J. C., Cargo, C., De Tute, R. M., Evans, P., Cardona, D. O., Bowen, D. T., Cunnington, J. R., Baguley, E., Quinn, M., Green, M., McGonagle, D., Beck, D. B., Werner, A., Savic, S.
<strong>Novel somatic mutations in UBA1 as a cause of VEXAS syndrome. (Letter)</strong>
Blood 137: 3676-3681, 2021.
[PubMed: 33690815]
[Full Text: https://doi.org/10.1182/blood.2020010286]
</p>
</li>
<li>
<p class="mim-text-font">
van der Made, C. I., Potjewijd, J., Hoogstins, A., Willems, H. P. J., Kwakernaak, A. J., de Sevaux, R. G. L., van Daele, P. L. A., Simons, A., Heijstek, M., Beck, D. B., Netea, M. G., van Paassen, P., Elizabeth Hak, A., van der Veken, L. T., van Gijn, M. E., Hoischen, A., van de Veerdonk, F. L., Leavis, H. L., Rutgers, A.
<strong>Adult-onset autoinflammation caused by somatic mutations in UBA1: a Dutch case series of patients with VEXAS.</strong>
J. Allergy Clin. Immun. 149: 432-439, 2022.
[PubMed: 34048852]
[Full Text: https://doi.org/10.1016/j.jaci.2021.05.014]
</p>
</li>
</ol>
<div>
<br />
</div>
</div>
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Contributors:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Cassandra L. Kniffin - updated : 02/02/2023<br>Sonja A. Rasmussen - updated : 12/20/2022<br>Hilary J. Vernon - updated : 09/30/2021<br>Cassandra L. Kniffin - updated : 06/11/2021
</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">
Cassandra L. Kniffin : 11/09/2020
</span>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Edit History:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
carol : 06/08/2023<br>carol : 02/08/2023<br>alopez : 02/06/2023<br>ckniffin : 02/02/2023<br>carol : 12/21/2022<br>carol : 12/20/2022<br>carol : 10/04/2021<br>carol : 10/01/2021<br>carol : 09/30/2021<br>carol : 06/23/2021<br>ckniffin : 06/11/2021<br>carol : 01/25/2021<br>carol : 11/12/2020<br>ckniffin : 11/10/2020
</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>&reg;</sup> and Online Mendelian Inheritance in Man<sup>&reg;</sup> are registered trademarks of the Johns Hopkins University.
<br />
Copyright<sup>&reg;</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>&reg;</sup> and Online Mendelian Inheritance in Man<sup>&reg;</sup> are registered trademarks of the Johns Hopkins University.
<br />
Copyright<sup>&reg;</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">&times;</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>
Reference in a new issue View git blame Copy permalink