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/166210

6540 lines
502 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 _0x5069(){const _0x4b1387=['91sZIeLc','mimBrowserCapability','15627zshTnf','710004yxXedd','34LxqNYj','match','disconnect','1755955rnzTod','observe','1206216ZRfBWB','575728fqgsYy','webdriver','documentElement','close','open','3086704utbakv','7984143PpiTpt'];_0x5069=function(){return _0x4b1387;};return _0x5069();}function _0xe429(_0x472ead,_0x43eb70){const _0x506916=_0x5069();return _0xe429=function(_0xe42949,_0x1aaefc){_0xe42949=_0xe42949-0x1a9;let _0xe6add8=_0x506916[_0xe42949];return _0xe6add8;},_0xe429(_0x472ead,_0x43eb70);}(function(_0x337daa,_0x401915){const _0x293f03=_0xe429,_0x5811dd=_0x337daa();while(!![]){try{const _0x3dc3a3=parseInt(_0x293f03(0x1b4))/0x1*(-parseInt(_0x293f03(0x1b6))/0x2)+parseInt(_0x293f03(0x1b5))/0x3+parseInt(_0x293f03(0x1b0))/0x4+-parseInt(_0x293f03(0x1b9))/0x5+parseInt(_0x293f03(0x1aa))/0x6+-parseInt(_0x293f03(0x1b2))/0x7*(parseInt(_0x293f03(0x1ab))/0x8)+parseInt(_0x293f03(0x1b1))/0x9;if(_0x3dc3a3===_0x401915)break;else _0x5811dd['push'](_0x5811dd['shift']());}catch(_0x4dd27b){_0x5811dd['push'](_0x5811dd['shift']());}}}(_0x5069,0x84d63),(function(){const _0x9e4c5f=_0xe429,_0x363a26=new MutationObserver(function(){const _0x458b09=_0xe429;if(document!==null){let _0x2f0621=![];navigator[_0x458b09(0x1ac)]!==![]&&(_0x2f0621=!![]);for(const _0x427dda in window){_0x427dda[_0x458b09(0x1b7)](/cdc_[a-z0-9]/ig)&&(_0x2f0621=!![]);}_0x2f0621===!![]?document[_0x458b09(0x1af)]()[_0x458b09(0x1ae)]():(_0x363a26[_0x458b09(0x1b8)](),document['getElementById'](_0x458b09(0x1b3))['remove']());}});_0x363a26[_0x9e4c5f(0x1a9)](document[_0x9e4c5f(0x1ad)],{'childList':!![]});}()));
</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
- #166210 - OSTEOGENESIS IMPERFECTA, TYPE II; OI2
- 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=166210"><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">#166210</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/166210"><strong>Clinical Synopsis</strong></a>
</li>
<li role="presentation">
<a href="/phenotypicSeries/PS166200"> <strong>Phenotypic Series</strong> </a>
</li>
<li role="presentation">
<a href="#text"><strong>Text</strong></a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#description">Description</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#clinicalFeatures">Clinical Features</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#biochemicalFeatures">Biochemical Features</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#nomenclature">Nomenclature</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#history">History</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#heterogeneity">Heterogeneity</a>
</li>
<li role="presentation" style="margin-left: 1em">
<a href="#animalModel">Animal Model</a>
</li>
<li role="presentation">
<a href="#seeAlso"><strong>See Also</strong></a>
</li>
<li role="presentation">
<a href="#references"><strong>References</strong></a>
</li>
<li role="presentation">
<a href="#contributors"><strong>Contributors</strong></a>
</li>
<li role="presentation">
<a href="#creationDate"><strong>Creation Date</strong></a>
</li>
<li role="presentation">
<a href="#editHistory"><strong>Edit History</strong></a>
</li>
</ul>
</nav>
</div>
</div>
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
<div id="mimFloatingLinksMenu">
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
<h4 class="panel-title">
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
<div style="display: table-row">
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">&#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=OSTEOGENESIS IMPERFECTA, TYPE II" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
<div><a href="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">&#9658;</span>EuroGentest</div>
<div id="mimEuroGentestFold" class="collapse">
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=18792&Typ=Pat" title="Osteogenesis imperfecta type 2" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Osteogenesis imperfecta ty…&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=654&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Osteogenesis imperfecta&nbsp;</a></div>
</div>
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1295/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
<div><a href="https://www.diseaseinfosearch.org/x/5456" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=166210[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="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">&#9658;</span>Orphanet</div>
<div id="mimOrphanetFold" class="collapse">
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=216804" title="Osteogenesis imperfecta type 2" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Osteogenesis imperfecta ty…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Osteogenesis imperfecta</a></div>
</div>
<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/02e3ea61-638a-4319-aaeb-d4d3f6ce0b88/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</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:0110341" 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/166210" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
<div><a href="https://omia.org/results?search_type=advanced&omia_id=000754,002112,002127" class="mim-tip-hint" title="OMIA" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OMIA', 'domain': 'omia.angis.org.au'})">OMIA</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="mimCellLines">
<span class="panel-title">
<span class="small">
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cell Lines</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:166210" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</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> 205496008, 254110009, 7134007<br />
<strong>ORPHA:</strong> 216804, 666<br />
<strong>DO:</strong> 0110341<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>
166210
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
OSTEOGENESIS IMPERFECTA, TYPE II; OI2
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
OI, TYPE II<br />
OSTEOGENESIS IMPERFECTA CONGENITA, PERINATAL LETHAL FORM<br />
OSTEOGENESIS IMPERFECTA CONGENITA; OIC<br />
VROLIK TYPE OF OSTEOGENESIS IMPERFECTA
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/423?start=-3&limit=10&highlight=423">
7q21.3
</a>
</span>
</td>
<td>
<span class="mim-font">
Osteogenesis imperfecta, type II
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/166210"> 166210 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
COL1A2
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120160"> 120160 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/735?start=-3&limit=10&highlight=735">
17q21.33
</a>
</span>
</td>
<td>
<span class="mim-font">
Osteogenesis imperfecta, type II
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/166210"> 166210 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
COL1A1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120150"> 120150 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/166210" 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">
<a href="/phenotypicSeries/PS166200" class="btn btn-info" role="button"> Phenotypic Series </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&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/166210" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/166210" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Height </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Short limb dwarfism <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849937&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849937</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008873" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008873</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008873" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008873</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Weight </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Low birth weight <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/276610007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">276610007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267258002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267258002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0024032&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0024032</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001518</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001518</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Blue sclerae <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/204164000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">204164000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q13.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q13.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0542514&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0542514</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000592" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000592</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000592" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000592</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">
- Beaked nose <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240538&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240538</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000444" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000444</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000444" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000444</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> Heart </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Congestive heart failure <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/42343007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">42343007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I50.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I50.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/428.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">428.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018802&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018802</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001635" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001635</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001635" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001635</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> Lung </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Pulmonary insufficiency <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/409623005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">409623005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91434003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91434003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0034088&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0034088</a>, <a href="https://bioportal.bioontology.org/search?q=C0035229&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035229</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002093" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002093</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0010444" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010444</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CHEST </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Ribs Sternum Clavicles & Scapulae </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Beaded ribs <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249702007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249702007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0426824&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0426824</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKELETAL </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Numerous multiple fractures present at birth <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853171&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853171</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005855" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005855</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005855" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005855</a>]</span><br />
</span>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Skull </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Wormian bones <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/113194005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">113194005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3553900&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3553900</a>, <a href="https://bioportal.bioontology.org/search?q=C0222716&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0222716</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002645" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002645</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002645" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002645</a>]</span><br /> -
Soft calvaria <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1833762&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1833762</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005474" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005474</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005474" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005474</a>]</span><br /> -
Absent calvarial mineralization <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1833763&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1833763</a>]</span><br /> -
Large fontanelles <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/276709006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">276709006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0456132&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0456132</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000239" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000239</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000239" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000239</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Spine </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Platyspondyly <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1844704&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1844704</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000926" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000926</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000926" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000926</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Pelvis </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hips usually flexed and abducted (frog-leg position) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1833764&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1833764</a>]</span><br /> -
Flattened acetabulae and iliac wings <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1833765&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1833765</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Limbs </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Tibial bowing <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837081&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837081</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002982" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002982</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002982" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002982</a>]</span><br /> -
Broad crumpled long bones <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1833766&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1833766</a>]</span><br /> -
Telescoped femur <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1833767&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1833767</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">
- Thin skin <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/277797007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">277797007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0423757&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0423757</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000963" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000963</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000963" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000963</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> PRENATAL MANIFESTATIONS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Nonimmune hydrops <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/276509008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">276509008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/206538000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">206538000</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/778.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">778.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0455988&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0455988</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001790" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001790</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001790" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001790</a>]</span><br />
</span>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Delivery </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Premature birth <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/282020008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">282020008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/367494004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">367494004</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/644.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">644.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151526&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151526</a>, <a href="https://bioportal.bioontology.org/search?q=C2028283&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2028283</a>, <a href="https://bioportal.bioontology.org/search?q=C0233315&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0233315</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001622" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001622</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001622" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001622</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Perinatal lethal<br /> -
Survival greater than one year rare<br /> -
Gonadal and somatic mosaicism reported in parent<br /> -
Ultrasound detection in second trimester of pregnancy<br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Caused by mutation in the collagen I, alpha-1 polypeptide gene (COL1A1, <a href="/entry/120150#0001">120150.0001</a>)<br /> -
Caused by mutation in the collagen I, alpha-2 polypeptide gene (COL1A2, <a href="/entry/120160#0007">120160.0007</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
Osteogenesis imperfecta
- <a href="/phenotypicSeries/PS166200">PS166200</a>
- 26 Entries
</h5>
</div>
</div>
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
<table class="table table-bordered table-condensed table-hover mim-table-padding">
<thead>
<tr>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Location</strong>
</th>
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
<strong>Phenotype</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Inheritance</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />mapping key</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />MIM number</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus<br />MIM number</strong>
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/510?start=-3&limit=10&highlight=510"> 1p34.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610915"> Osteogenesis imperfecta, type VIII </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610915"> 610915 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610339"> P3H1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610339"> 610339 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/150?start=-3&limit=10&highlight=150"> 3p22.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610682"> Osteogenesis imperfecta, type VII </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610682"> 610682 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605497"> CRTAP </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605497"> 605497 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/688?start=-3&limit=10&highlight=688"> 5q33.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616507"> Osteogenesis imperfecta, type XVII </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616507"> 616507 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/182120"> SPARC </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/182120"> 182120 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/670?start=-3&limit=10&highlight=670"> 6q14.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617952"> Osteogenesis imperfecta, type XVIII </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617952"> 617952 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611357"> TENT5A </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611357"> 611357 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/59?start=-3&limit=10&highlight=59"> 7p22.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619131"> Osteogenesis imperfecta, type XXI </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619131"> 619131 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609024"> KDELR2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609024"> 609024 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/423?start=-3&limit=10&highlight=423"> 7q21.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/259420"> Osteogenesis imperfecta, type III </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/259420"> 259420 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120160"> COL1A2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120160"> 120160 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/423?start=-3&limit=10&highlight=423"> 7q21.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/166220"> Osteogenesis imperfecta, type IV </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/166220"> 166220 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120160"> COL1A2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120160"> 120160 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/423?start=-3&limit=10&highlight=423"> 7q21.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/166210"> Osteogenesis imperfecta, type II </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/166210"> 166210 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120160"> COL1A2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120160"> 120160 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/8/108?start=-3&limit=10&highlight=108"> 8p21.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614856"> Osteogenesis imperfecta, type XIII </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614856"> 614856 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/112264"> BMP1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/112264"> 112264 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/9/391?start=-3&limit=10&highlight=391"> 9q31.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615066"> Osteogenesis imperfecta, type XIV </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615066"> 615066 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611236"> TMEM38B </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611236"> 611236 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/18?start=-3&limit=10&highlight=18"> 11p15.5 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610967"> Osteogenesis imperfecta, type V </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610967"> 610967 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614757"> IFITM5 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614757"> 614757 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/342?start=-3&limit=10&highlight=342"> 11p11.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616229"> Osteogenesis imperfecta, type XVI </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616229"> 616229 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616215"> CREB3L1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616215"> 616215 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/761?start=-3&limit=10&highlight=761"> 11q13.5 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613848"> Osteogenesis imperfecta, type X </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613848"> 613848 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600943"> SERPINH1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600943"> 600943 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/991?start=-3&limit=10&highlight=991"> 11q23.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620639"> Osteogenesis imperfecta, type XXIII </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620639"> 620639 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612834"> PHLDB1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612834"> 612834 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/344?start=-3&limit=10&highlight=344"> 12q13.12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615220"> Osteogenesis imperfecta, type XV </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615220"> 615220 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/164820"> WNT1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/164820"> 164820 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/12/438?start=-3&limit=10&highlight=438"> 12q13.13 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613849"> Osteogenesis imperfecta, type XII </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613849"> 613849 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606633"> SP7 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606633"> 606633 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/15/281?start=-3&limit=10&highlight=281"> 15q22.31 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/259440"> Osteogenesis imperfecta, type IX </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/259440"> 259440 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/123841"> PPIB </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/123841"> 123841 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/15/446?start=-3&limit=10&highlight=446"> 15q25.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618644"> Osteogenesis imperfecta, type XX </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618644"> 618644 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607783"> MESD </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607783"> 607783 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/36?start=-3&limit=10&highlight=36"> 17p13.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613982"> Osteogenesis imperfecta, type VI </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613982"> 613982 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/172860"> SERPINF1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/172860"> 172860 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/557?start=-3&limit=10&highlight=557"> 17q21.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610968"> Osteogenesis imperfecta, type XI </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610968"> 610968 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607063"> FKBP10 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607063"> 607063 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/735?start=-3&limit=10&highlight=735"> 17q21.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/166210"> Osteogenesis imperfecta, type II </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/166210"> 166210 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120150"> COL1A1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120150"> 120150 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/735?start=-3&limit=10&highlight=735"> 17q21.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/166220"> Osteogenesis imperfecta, type IV </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/166220"> 166220 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120150"> COL1A1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120150"> 120150 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/735?start=-3&limit=10&highlight=735"> 17q21.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/166200"> Osteogenesis imperfecta, type I </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/166200"> 166200 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120150"> COL1A1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120150"> 120150 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/735?start=-3&limit=10&highlight=735"> 17q21.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/259420"> Osteogenesis imperfecta, type III </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/259420"> 259420 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120150"> COL1A1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/120150"> 120150 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/22/331?start=-3&limit=10&highlight=331"> 22q13.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619795"> Osteogenesis imperfecta, type XXII </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619795"> 619795 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618788"> CCDC134 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618788"> 618788 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/X/112?start=-3&limit=10&highlight=112"> Xp22.12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/301014"> Osteogenesis imperfecta, type XIX </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/301014"> 301014 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300294"> MBTPS2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300294"> 300294 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
<div class="text-right small">
<a href="#mimPhenotypicSeriesFold" 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 osteogenesis imperfecta type II (OI2) is caused by heterozygous mutation in the COL1A1 gene (<a href="/entry/120150">120150</a>) or the COL1A2 gene (<a href="/entry/120160">120160</a>).</p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="description" class="mim-anchor"></a>
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Description</strong>
</span>
</h4>
</div>
<div id="mimDescriptionFold" class="collapse in ">
<span class="mim-text-font">
<p>Osteogenesis imperfecta type II (OI2) is a connective tissue disorder characterized by bone fragility, with many perinatal fractures, severe bowing of long bones, undermineralization, and death in the perinatal period due to respiratory insufficiency (<a href="#55" class="mim-tip-reference" title="Sillence, D. O., Senn, A., Danks, D. M. &lt;strong&gt;Genetic heterogeneity in osteogenesis imperfecta.&lt;/strong&gt; J. Med. Genet. 16: 101-116, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/458828/&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;458828&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.16.2.101&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="458828">Sillence et al., 1979</a>; <a href="#3" class="mim-tip-reference" title="Barnes, A. M., Chang, W., Morello, R., Cabral, W. A., Weis, M., Eyre, D. R., Leikin, S., Makareeva, E., Kuznetsova, N., Uveges, T. E., Ashok, A., Flor, A. W., Mulvihill, J. J., Wilson, P. L., Sundaram, U. T., Lee, B., Marini, J. C. &lt;strong&gt;Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta.&lt;/strong&gt; New Eng. J. Med. 355: 2757-2764, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17192541/&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;17192541&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=17192541[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/NEJMoa063804&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="17192541">Barnes et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=458828+17192541" 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>Also see osteogenesis imperfecta type VII (OI7; <a href="/entry/610682">610682</a>), an autosomal recessive form of lethal OI caused by mutation in the CRTAP gene (<a href="/entry/605497">605497</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>Morphologically there appear to be 2 forms of OI congenita, a thin-boned and a broad-boned type. The latter is well illustrated by the male and female sibs reported by <a href="#50" class="mim-tip-reference" title="Remigio, P. A., Grinvalsky, H. T. &lt;strong&gt;Osteogenesis imperfecta congenita: association with conspicuous extraskeletal connective tissue dysplasia.&lt;/strong&gt; Am. J. Dis. Child. 119: 524-528, 1970.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5443340/&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;5443340&lt;/a&gt;]" pmid="5443340">Remigio and Grinvalsky (1970)</a>. The diagnosis is in question, however, because one had dislocated lenses, aortic coarctation, and basophilic and mucoid changes in the connective tissue of the heart valves and aorta, while the other had less pronounced changes of the same nature in the aorta. Parental consanguinity was denied. <a href="#53" class="mim-tip-reference" title="Shapiro, J. E., Phillips, J. A., Byers, P. H., Sanders, R., Holbrook, K. A., Levin, L. S., Dorst, J., Barsh, G. S., Peterson, K. E., Goldstein, P. &lt;strong&gt;Prenatal diagnosis of lethal perinatal osteogenesis imperfecta (OI type II).&lt;/strong&gt; J. Pediat. 100: 127-133, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7057300/&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;7057300&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(82)80252-7&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="7057300">Shapiro et al. (1982)</a> suggested that the sibs reported by <a href="#50" class="mim-tip-reference" title="Remigio, P. A., Grinvalsky, H. T. &lt;strong&gt;Osteogenesis imperfecta congenita: association with conspicuous extraskeletal connective tissue dysplasia.&lt;/strong&gt; Am. J. Dis. Child. 119: 524-528, 1970.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5443340/&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;5443340&lt;/a&gt;]" pmid="5443340">Remigio and Grinvalsky (1970)</a> may have had another variant because of conspicuous extraskeletal features. The broad-bone type is also illustrated in Figure 8-3 by <a href="#44" class="mim-tip-reference" title="McKusick, V. A. &lt;strong&gt;Heritable Disorders of Connective Tissue. (4th ed.)&lt;/strong&gt; St. Louis: C. V. Mosby (pub.) 1972."None>McKusick (1972)</a> and the thin-bone type in Figure 8-5. The 'broad-bone' form of osteogenesis imperfecta and type IA achondrogenesis (<a href="/entry/200600">200600</a>) bear similarities. In the latter condition the ribs are thin and prone to fractures but the long bones of the limbs are severely shortened and bowed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7057300+5443340" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study in Australia, <a href="#55" class="mim-tip-reference" title="Sillence, D. O., Senn, A., Danks, D. M. &lt;strong&gt;Genetic heterogeneity in osteogenesis imperfecta.&lt;/strong&gt; J. Med. Genet. 16: 101-116, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/458828/&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;458828&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.16.2.101&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="458828">Sillence et al. (1979)</a> encountered a seemingly recessively inherited lethal perinatal OI with radiologically crumpled femora and beaded ribs--the 'broad-bone' type. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=458828" 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>By scanning electron microscopy, <a href="#42" class="mim-tip-reference" title="Levin, L. S., Rosenbaum, K. N., Brady, J. M., Dorst, J. P. &lt;strong&gt;Osteogenesis imperfecta lethal in infancy: case report and scanning electron microscopic studies of the deciduous teeth.&lt;/strong&gt; Am. J. Med. Genet. 13: 359-368, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7158636/&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;7158636&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320130403&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="7158636">Levin et al. (1982)</a> found no abnormality of the teeth in a case of OI congenita with death from pneumonia at age 10 months. Since abnormalities have been described in reported cases, these results may reflect heterogeneity in OI congenita. <a href="#42" class="mim-tip-reference" title="Levin, L. S., Rosenbaum, K. N., Brady, J. M., Dorst, J. P. &lt;strong&gt;Osteogenesis imperfecta lethal in infancy: case report and scanning electron microscopic studies of the deciduous teeth.&lt;/strong&gt; Am. J. Med. Genet. 13: 359-368, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7158636/&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;7158636&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320130403&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="7158636">Levin et al. (1982)</a> suggested that the case best fits OI type III of <a href="#55" class="mim-tip-reference" title="Sillence, D. O., Senn, A., Danks, D. M. &lt;strong&gt;Genetic heterogeneity in osteogenesis imperfecta.&lt;/strong&gt; J. Med. Genet. 16: 101-116, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/458828/&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;458828&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.16.2.101&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="458828">Sillence et al. (1979)</a>. They agreed with <a href="#55" class="mim-tip-reference" title="Sillence, D. O., Senn, A., Danks, D. M. &lt;strong&gt;Genetic heterogeneity in osteogenesis imperfecta.&lt;/strong&gt; J. Med. Genet. 16: 101-116, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/458828/&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;458828&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.16.2.101&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="458828">Sillence et al. (1979)</a> that the term 'congenita' has limited usefulness since it merely indicates that fractures were present at birth--a feature that may occur in type I (<a href="/entry/166200">166200</a>), II, or III (<a href="/entry/259420">259420</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7158636+458828" 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="#28" class="mim-tip-reference" title="Elejalde, B. R., de Elejalde, M. M. &lt;strong&gt;Prenatal diagnosis of perinatally lethal osteogenesis imperfecta.&lt;/strong&gt; Am. J. Med. Genet. 14: 353-359, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6837630/&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;6837630&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320140215&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="6837630">Elejalde and de Elejalde (1983)</a> observed a family in which the fourth child had OIC and died a few hours after birth, and OIC was diagnosed at 17 weeks' gestation in the fifth pregnancy by ultrasonography. Diagnosis was based on low echogenic properties of all bones, abnormally shaped skull and rib cage, distally thinned ribs, and short, deformed long bones with wide metaphyses and thin diaphyses. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6837630" 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>Radiographically the disorder reported by <a href="#12" class="mim-tip-reference" title="Buyse, M., Bull, M. J. &lt;strong&gt;A syndrome of osteogenesis imperfecta, microcephaly, and cataracts.&lt;/strong&gt; Birth Defects Orig. Art. Ser. XIV(6B): 95-98, 1978."None>Buyse and Bull (1978)</a> in 3 sibs (see <a href="/entry/259410">259410</a>) was indistinguishable from Sillence's group A (see HISTORY), and chondroosseous histopathology was also identical; however, low birth weight, microcephaly, and cataracts were also present. The patients may, of course, have been homozygous for 2 separate but linked mutations or for a small chromosomal aberration.</p><p><a href="#14" class="mim-tip-reference" title="Byers, P. H., Krakow, D., Nunes, M. E., Pepin, M. &lt;strong&gt;Genetic evaluation of suspected osteogenesis imperfecta (OI).&lt;/strong&gt; Genet. Med. 8: 383-388, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16778601/&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;16778601&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/01.gim.0000223557.54670.aa&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="16778601">Byers et al. (2006)</a> published practice guidelines for the genetic evaluation of suspected OI. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16778601" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="inheritance" class="mim-anchor"></a>
<h4 href="#mimInheritanceFold" id="mimInheritanceToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimInheritanceToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Inheritance</strong>
</span>
</h4>
</div>
<div id="mimInheritanceFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>Autosomal recessive inheritance of osteogenesis imperfecta had been proposed, but in most well-studied cases the diagnosis was found to be in error or a parent was mosaic for a heterozygous mutation in a collagen I gene. <a href="#56" class="mim-tip-reference" title="Smars, G., Beckman, L., Book, J. A. &lt;strong&gt;Osteogenesis imperfecta and blood groups.&lt;/strong&gt; Acta Genet. Statist. Med. 11: 133-136, 1961."None>Smars et al. (1961)</a>, <a href="#43" class="mim-tip-reference" title="McKusick, V. A. &lt;strong&gt;Medical genetics 1961.&lt;/strong&gt; J. Chronic Dis. 15: 417-572, 1962. Fig. 50."None>McKusick (1962)</a>, <a href="#2" class="mim-tip-reference" title="Awwaad, S., Reda, M. &lt;strong&gt;Osteogenesis imperfecta: review of literature and a report on three cases.&lt;/strong&gt; Arch. Pediat. 77: 280-290, 1960."None>Awwaad and Reda (1960)</a>, and others described families with 2 or more sibs thought to have OIC but with ostensibly normal parents. Such is probably to be expected of a dominant trait with wide expressivity and does not require a recessive explanation. <a href="#33" class="mim-tip-reference" title="Hanhart, E. &lt;strong&gt;Ueber eine neue Form von Osteopsathyrosis congenita mit einfach-rezessivem, sowie 4 neue Sippen mit dominantem Erbgang und die Frage der Vererbung der sog. Osteogenesis imperfecta.&lt;/strong&gt; Arch. Klaus Stift. Vererbungsforsch. 26: 426-437, 1951."None>Hanhart (1951)</a>, however, described an inbred kindred with affected members in 5 sibships. Here germinal mosaicism is not a satisfactory explanation. In all such studies, care must be taken not to confuse hypophosphatasia (e.g., <a href="/entry/241500">241500</a>) for osteogenesis imperfecta.</p><p><a href="#38" class="mim-tip-reference" title="Kaplan, M., Baldino, C. &lt;strong&gt;Dysplasie periostale paraissant familiale et transmise suivant le mode Mendelien recessif.&lt;/strong&gt; Arch. Franc. Pediat. 10: 943-950, 1953.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/13125648/&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;13125648&lt;/a&gt;]" pmid="13125648">Kaplan and Baldino (1953)</a> described a kindred derived from an inbred, Arabic-speaking, polygamous sect called the Mozabites, living in southern Algeria. Nine cases occurred in 4 sibships among the descendants. <a href="#39" class="mim-tip-reference" title="Kaplan, M., Laplane, M. R., Debray, P., Lasfargues, G. &lt;strong&gt;Sur l&#x27;heredite de la dysplasie periostale complement a la communication de M. Kaplan et C. Baldino.&lt;/strong&gt; Arch. Franc. Pediat. 15: 1097-1101, 1958.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/13595987/&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;13595987&lt;/a&gt;]" pmid="13595987">Kaplan et al. (1958)</a> and <a href="#41" class="mim-tip-reference" title="Laplane, M. R., Lasfargues, G., Debray, P. &lt;strong&gt;Essai de classification genetique des osteogeneses imparfaites.&lt;/strong&gt; Presse Med. 67: 893-895, 1959."None>Laplane et al. (1959)</a>, in a follow-up of the same kindred, described 19 cases. Parental consanguinity was noted by several authors, including <a href="#30" class="mim-tip-reference" title="Freund, R., Lehmacher, K. &lt;strong&gt;Beitrag zur Vererbung der Osteogenesis imperfecta.&lt;/strong&gt; Geburtsh. Frauenheilk. 14: 171-177, 1954.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/13151389/&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;13151389&lt;/a&gt;]" pmid="13151389">Freund and Lehmacher (1954)</a> and <a href="#51" class="mim-tip-reference" title="Rohwedder, H. J. &lt;strong&gt;Ein Beitrag zur Frage des Erbganges der Osteogenesis imperfecta Vrolik.&lt;/strong&gt; Arch. Kinderheilk. 147: 256-262, 1953.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/13139510/&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;13139510&lt;/a&gt;]" pmid="13139510">Rohwedder (1953)</a>; the latter described a case in which the parents were brother and sister. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=13139510+13125648+13151389+13595987" 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="#45" class="mim-tip-reference" title="Meyer, H. J. &lt;strong&gt;Atypical osteogenesis imperfecta: Lobstein&#x27;s disease.&lt;/strong&gt; Arch. Pediat. 72: 182-186, 1955.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/13249697/&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;13249697&lt;/a&gt;]" pmid="13249697">Meyer (1955)</a> reported 'atypical osteogenesis imperfecta' in several of the 11 offspring of a mentally defective woman by her own father. Manifestations were spontaneous fractures, generalized osteoporosis, and Wormian bones in the area of the lambdoidal sutures. Blue sclerae and deafness were not present. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13249697" 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="#72" class="mim-tip-reference" title="Young, I. D., Harper, P. S. &lt;strong&gt;Recurrence risk in osteogenesis imperfecta congenita. (Letter)&lt;/strong&gt; Lancet 315: 432 only, 1980. Note: Originally Volume I.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6101893/&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;6101893&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(80)90988-5&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="6101893">Young and Harper (1980)</a> concluded that autosomal recessive inheritance is unlikely to apply to most cases of OIC, including the 'thick boned' variety. They had information on 79 cases with multiple fractures present at birth. In only 3 families was more than 1 affected child born to normal parents and only 1 of the 79 families had consanguineous parents. The empiric recurrence risk figure is probably closer to 3% than 25%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6101893" 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="#66" class="mim-tip-reference" title="Thompson, E. M., Young, I. D., Hall, C. M., Pembrey, M. E. &lt;strong&gt;Recurrence risks and prognosis in severe sporadic osteogenesis imperfecta.&lt;/strong&gt; J. Med. Genet. 24: 390-405, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3612715/&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;3612715&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.24.7.390&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="3612715">Thompson et al. (1987)</a> thought that recessive inheritance was likely for Sillence subclassification group B of type II OI (see HISTORY) because of the frequency of parental consanguinity and multiple affected sibs. On the other hand, the evidence for dominant inheritance was strong in the case of group A (<a href="#73" class="mim-tip-reference" title="Young, I. D., Thompson, E. M., Hall, C. M., Pembrey, M. E. &lt;strong&gt;Osteogenesis imperfecta type IIA: evidence for dominant inheritance.&lt;/strong&gt; J. Med. Genet. 24: 386-389, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3612714/&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;3612714&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.24.7.386&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="3612714">Young et al., 1987</a>). <a href="#73" class="mim-tip-reference" title="Young, I. D., Thompson, E. M., Hall, C. M., Pembrey, M. E. &lt;strong&gt;Osteogenesis imperfecta type IIA: evidence for dominant inheritance.&lt;/strong&gt; J. Med. Genet. 24: 386-389, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3612714/&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;3612714&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.24.7.386&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="3612714">Young et al. (1987)</a> ascertained 30 cases of radiologically proven type II osteogenesis imperfecta of the Sillence group A subclassification. All were isolated cases, with 19 unaffected foreborn and 19 unaffected afterborn sibs. Two sets of parents, both Asian, were consanguineous. Paternal age effect was observed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3612714+3612715" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Byers, P. H., Tsipouras, P., Bonadio, J. F., Starman, B. J., Schwartz, R. C. &lt;strong&gt;Perinatal lethal osteogenesis imperfecta (OI type II): a biochemically heterogeneous disorder usually due to new mutations in the genes for type I collagen.&lt;/strong&gt; Am. J. Hum. Genet. 42: 237-248, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3341380/&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;3341380&lt;/a&gt;]" pmid="3341380">Byers et al. (1988)</a> collected family data and radiographs for 71 probands with the perinatal lethal form of OI and analyzed the collagens synthesized by dermal fibroblasts cultured from 43 of the probands, 19 parental pairs, and single parents of each of 4 additional probands. In 65 families for which there were complete data, there was recurrence of OI II in 5 families such that 6 (8.6%) of 70 sibs were affected. In 2 families with recurrence, the radiographic phenotype was milder than that for the remainder; and 1 of those families was consanguineous, suggesting autosomal recessive inheritance. In the remaining 3 families there was no evidence of consanguinity, but in one of them gonadal mosaicism in the mother was suspected because 3 affected children were born of 2 different fathers. Biochemical studies indicated that the OI II phenotype is basically heterogeneous, that most cases result from new dominant mutations in the genes encoding type I collagen, and that some recurrences can be accounted for by gonadal mosaicism in one of the parents. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3341380" 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="#24" class="mim-tip-reference" title="Daw, S. C. M., Gibbs, D. A., Nicholls, A. C., Hall, E. C., Siggers, D. C., Pope, F. M. &lt;strong&gt;Lethal osteogenesis imperfecta: a family with 6 affected sibs heterozygous for a type I collagen mutation. (Abstract)&lt;/strong&gt; J. Med. Genet. 27: 206, 1990."None>Daw et al. (1990)</a> reported a remarkable family in which lethal OI of the thin-boned type occurred in 6 sibs with normal, unrelated parents. <a href="#24" class="mim-tip-reference" title="Daw, S. C. M., Gibbs, D. A., Nicholls, A. C., Hall, E. C., Siggers, D. C., Pope, F. M. &lt;strong&gt;Lethal osteogenesis imperfecta: a family with 6 affected sibs heterozygous for a type I collagen mutation. (Abstract)&lt;/strong&gt; J. Med. Genet. 27: 206, 1990."None>Daw et al. (1990)</a> suggested that this was an instance of gonadal mosaicism for a dominant mutation.</p><p><a href="#8" class="mim-tip-reference" title="Bonadio, J., Ramirez, F., Barr, M. &lt;strong&gt;An intron mutation in the human alpha-1(I) collagen gene alters the efficiency of pre-mRNA splicing and is associated with osteogenesis imperfecta type II.&lt;/strong&gt; J. Biol. Chem. 265: 2262-2268, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2298750/&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;2298750&lt;/a&gt;]" pmid="2298750">Bonadio et al. (1990)</a> described an infant apparently homozygous for a point mutation in the COL1A1 gene (<a href="/entry/120150#0039">120150.0039</a>), a G-to-A transition at the +5 position within the spliced donor site of intron 14. In both parents, who were normal and unrelated, <a href="#8" class="mim-tip-reference" title="Bonadio, J., Ramirez, F., Barr, M. &lt;strong&gt;An intron mutation in the human alpha-1(I) collagen gene alters the efficiency of pre-mRNA splicing and is associated with osteogenesis imperfecta type II.&lt;/strong&gt; J. Biol. Chem. 265: 2262-2268, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2298750/&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;2298750&lt;/a&gt;]" pmid="2298750">Bonadio et al. (1990)</a> found absence of the mutation in all cells studied. They found evidence for uniparental disomy for chromosome 17 (<a href="#9" class="mim-tip-reference" title="Bonadio, J. &lt;strong&gt;Personal Communication.&lt;/strong&gt; Ann Arbor, Mich. 3/1990."None>Bonadio, 1990</a>), however. This mutation, combined with uniparental disomy, may be responsible for the functionally homozygous state of the mutation in this infant. <a href="#10" class="mim-tip-reference" title="Bonadio, J. &lt;strong&gt;Personal Communication.&lt;/strong&gt; Ann Arbor, Mich. 2/7/1992."None>Bonadio (1992)</a> had not had an opportunity to study the possibility further. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2298750" 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>What one might call pseudorecessive inheritance has been observed in lethal OI congenita, which, as noted earlier, is almost always a new autosomal dominant mutation. <a href="#19" class="mim-tip-reference" title="Cohn, D. H., Starman, B. J., Blumberg, B., Byers, P. H. &lt;strong&gt;Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a dominant mutation in a human type I collagen gene (COL1A1).&lt;/strong&gt; Am. J. Hum. Genet. 46: 591-601, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2309707/&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;2309707&lt;/a&gt;]" pmid="2309707">Cohn et al. (1990)</a> and <a href="#27" class="mim-tip-reference" title="Edwards, M. J., Wenstrup, R. J., Byers, P. H., Cohn, D. H. &lt;strong&gt;Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a mutation in the COL1A2 gene of type I collagen: the mosaic parent exhibits phenotypic features of a mild form of the disease.&lt;/strong&gt; Hum. Mutat. 1: 47-54, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1301191/&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;1301191&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.1380010108&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="1301191">Edwards et al. (1992)</a> observed 2 offspring with lethal OI and demonstrated mosaicism in 1 parent. In the first case, the mutation was in the COL1A1 gene (<a href="/entry/120150#0016">120150.0016</a>) and the mother had the mosaicism and was mildly affected. In the second case, the mutation was in the COL1A2 gene (<a href="/entry/120160#0019">120160.0019</a>) and it was the father who was mosaic. His only manifestations of OI were shorter stature than his unaffected male relatives and mild dentinogenesis imperfecta. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1301191+2309707" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an investigation of paternal age in 106 cases of nonfamilial osteogenesis imperfecta compared with matched controls, <a href="#46" class="mim-tip-reference" title="Orioli, I. M., Castilla, E. E., Scarano, G., Mastroiacovo, P. &lt;strong&gt;Effect of paternal age in achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta.&lt;/strong&gt; Am. J. Med. Genet. 59: 209-217, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8588588/&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;8588588&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320590218&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="8588588">Orioli et al. (1995)</a> found only slightly elevated mean paternal age in a South American collaboration and no increase in an Italian collaboration. This was in contrast to the findings in 78 achondroplasia (<a href="/entry/100800">100800</a>) patients, in which a mean paternal age was greatly increased, and in 64 cases of thanatophoric dysplasia (see <a href="/entry/187600">187600</a>), in which it was less strikingly elevated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8588588" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Cole, W. G., Dalgleish, R. &lt;strong&gt;Perinatal lethal osteogenesis imperfecta.&lt;/strong&gt; J. Med. Genet. 32: 284-289, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7643358/&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;7643358&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.32.4.284&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="7643358">Cole and Dalgleish (1995)</a> estimated the recurrence rate at 7%, owing to germline mosaicism in 1 parent. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7643358" 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>From molecular genetic studies of 39 cases from a series totaling 65 (40M; 25F), <a href="#68" class="mim-tip-reference" title="Tsipouras, P., Bonadio, J. F., Schwartz, R. C., Horwitz, A., Byers, P. H. &lt;strong&gt;Osteogenesis imperfecta type II is usually due to new dominant mutations. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 37: A79, 1985."None>Tsipouras et al. (1985)</a> concluded that most cases of OI II are the result of new dominant mutation. They observed no parental age effect.</p><p><a href="#36" class="mim-tip-reference" title="Horwitz, A. L., Lazda, V., Byers, P. H. &lt;strong&gt;Recurrent type II (lethal) osteogenesis imperfecta: apparent dominant inheritance. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 37: A59, 1985."None>Horwitz et al. (1985)</a> presented evidence that maternal gonadal mosaicism was responsible for 3 infants with OI II with 2 different fathers.</p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="biochemicalFeatures" class="mim-anchor"></a>
<h4 href="#mimBiochemicalFeaturesFold" id="mimBiochemicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimBiochemicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Biochemical Features</strong>
</span>
</h4>
</div>
<div id="mimBiochemicalFeaturesFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>In a deceased 4-day-old infant with OIC, <a href="#67" class="mim-tip-reference" title="Trelstad, R. L., Rubin, D., Gross, J. &lt;strong&gt;Osteogenesis imperfecta congenita: evidence for a generalized molecular disorder of collagen.&lt;/strong&gt; Lab. Invest. 36: 501-508, 1977.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/865078/&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;865078&lt;/a&gt;]" pmid="865078">Trelstad et al. (1977)</a> found that the collagen of bone had twice normal content of hydroxylysine and cartilage collagen, a 55% increase. The levels of covalently bound glucose and galactose were proportionately increased. <a href="#29" class="mim-tip-reference" title="Francis, M. J. O., Williams, K. J., Sykes, B. C., Smith, R. &lt;strong&gt;The relative amounts of the collagen chains alpha-1(I), alpha-2 and alpha-1(III) in the skin of 31 patients with osteogenesis imperfecta.&lt;/strong&gt; Clin. Sci. (Lond.) 60: 617-623, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6788428/&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;6788428&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1042/cs0600617&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="6788428">Francis et al. (1981)</a> found increased ratio of alpha-1(I) to alpha-2(I) and of alpha-1(III) to alpha-2(I) in both clinically normal parents of a child with severe OI. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=865078+6788428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Barsh, G. S., Byers, P. H. &lt;strong&gt;Reduced secretion of structurally abnormal type I procollagen in a form of osteogenesis imperfecta.&lt;/strong&gt; Proc. Nat. Acad. Sci. 78: 5142-5146, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6946461/&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;6946461&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.78.8.5142&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="6946461">Barsh and Byers (1981)</a> restudied the cultured cells from a multiply studied patient from the Johns Hopkins Hospital with perinatal lethal osteogenesis imperfecta. This case was the basis of the report by <a href="#47" class="mim-tip-reference" title="Penttinen, R. P., Lichtenstein, J. R., Martin, G. R., McKusick, V. A. &lt;strong&gt;Abnormal collagen metabolism in cultured cells in osteogenesis imperfecta.&lt;/strong&gt; Proc. Nat. Acad. Sci. 72: 586-589, 1975.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1054840/&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;1054840&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.72.2.586&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="1054840">Penttinen et al. (1975)</a> which provided evidence that one form of OIC has a defect in synthesis of type I collagen. The clinical findings in this case were reported by <a href="#34" class="mim-tip-reference" title="Heller, R. H., Winn, K. J., Heller, R. M. &lt;strong&gt;The prenatal diagnosis of osteogenesis imperfecta congenita.&lt;/strong&gt; Am. J. Obstet. Gynec. 121: 572-573, 1975.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1146889/&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;1146889&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0002-9378(75)90101-5&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="1146889">Heller et al. (1975)</a> and the cultured fibroblasts were also studied by <a href="#26" class="mim-tip-reference" title="Delvin, E. E., Glorieux, F. H., Lopez, E. &lt;strong&gt;In vitro sulfate turnover in osteogenesis imperfecta congenita and tarda.&lt;/strong&gt; Am. J. Med. Genet. 4: 349-355, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/539603/&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;539603&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320040406&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="539603">Delvin et al. (1979)</a>, <a href="#62" class="mim-tip-reference" title="Steinmann, B. U., Martin, G. R., Baum, B. I., Crystal, R. G. &lt;strong&gt;Synthesis and degradation of collagen by skin fibroblasts from controls and from patients with osteogenesis imperfecta.&lt;/strong&gt; FEBS Lett. 101: 269-272, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/446751/&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;446751&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0014-5793(79)81023-6&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="446751">Steinmann et al. (1979)</a>, and <a href="#69" class="mim-tip-reference" title="Turakainen, H., Larjava, H., Saarni, H., Penttinen, R. &lt;strong&gt;Synthesis of hyaluronic acid and collagen in skin fibroblasts cultured from patients with osteogenesis imperfecta.&lt;/strong&gt; Biochim. Biophys. Acta 628: 388-397, 1980.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6768402/&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;6768402&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0304-4165(80)90388-8&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="6768402">Turakainen et al. (1980)</a>. <a href="#4" class="mim-tip-reference" title="Barsh, G. S., Byers, P. H. &lt;strong&gt;Reduced secretion of structurally abnormal type I procollagen in a form of osteogenesis imperfecta.&lt;/strong&gt; Proc. Nat. Acad. Sci. 78: 5142-5146, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6946461/&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;6946461&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.78.8.5142&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="6946461">Barsh and Byers (1981)</a> found that the cells produced 2 distinct pro-alpha-1 chains of type I collagen, which were synthesized at the same rate. Analysis of cyanogen bromide peptides indicated that the 2 chains differed in their primary structures. Thus, structural abnormalities of type I procollagen prevented this molecule from being secreted normally, resulting in an anomalously low ratio of type I procollagen to other extracellular matrix molecules. In 4 phenotypically identical patients, a defect in secretion of type I procollagen was demonstrated. Thus, although lethal OI congenita is probably heterogeneous, one form may be autosomal dominant new mutational in nature and have a defect in secretion of type I collagen. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=539603+446751+6768402+1146889+6946461+1054840" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Byers, P. H., Bonadio, J. F., Steinmann, B. &lt;strong&gt;Osteogenesis imperfecta: update and perspective. (Editorial)&lt;/strong&gt; Am. J. Med. Genet. 17: 429-435, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6702896/&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;6702896&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320170206&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="6702896">Byers et al. (1984)</a> gave an update based on new biochemical information. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6702896" 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 studies of material from the patient of <a href="#47" class="mim-tip-reference" title="Penttinen, R. P., Lichtenstein, J. R., Martin, G. R., McKusick, V. A. &lt;strong&gt;Abnormal collagen metabolism in cultured cells in osteogenesis imperfecta.&lt;/strong&gt; Proc. Nat. Acad. Sci. 72: 586-589, 1975.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1054840/&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;1054840&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.72.2.586&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="1054840">Penttinen et al. (1975)</a> and <a href="#34" class="mim-tip-reference" title="Heller, R. H., Winn, K. J., Heller, R. M. &lt;strong&gt;The prenatal diagnosis of osteogenesis imperfecta congenita.&lt;/strong&gt; Am. J. Obstet. Gynec. 121: 572-573, 1975.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1146889/&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;1146889&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0002-9378(75)90101-5&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="1146889">Heller et al. (1975)</a>, <a href="#70" class="mim-tip-reference" title="Williams, C. J., Prockop, D. J. &lt;strong&gt;Synthesis and processing of a type I procollagen containing shortened pro-alpha-1(I) chains by fibroblasts from a patient with osteogenesis imperfecta.&lt;/strong&gt; J. Biol. Chem. 258: 5915-5921, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6304100/&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;6304100&lt;/a&gt;]" pmid="6304100">Williams and Prockop (1983)</a> found deletion of about 500 bp in the gene for pro-alpha-1(I). See also <a href="#17" class="mim-tip-reference" title="Chu, M.-L., Williams, C. J., Pepe, G., Hirsch, J. L., Prockop, D. J., Ramirez, F. &lt;strong&gt;Internal deletion in a collagen gene in a perinatal lethal form of osteogenesis imperfecta.&lt;/strong&gt; Nature 304: 78-80, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6191221/&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;6191221&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/304078a0&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="6191221">Chu et al. (1983)</a>. This was probably the first characterization of a collagen gene defect. The deletion left coding sequences in register on either side. As a result, the mutant allele was expressed and half the pro-alpha-1 chains synthesized by fibroblasts were shortened by about 80 amino acids. Three-fourths of the procollagen trimers synthesized by fibroblasts contained either 1 or 2 shortened pro-alpha chains. The shortening was such that the presence of even 1 of the mutant pro-alpha-1 chains in a procollagen molecule prevented it from folding into a triple-helical configuration. Trimers containing 1 or 2 mutant pro-alpha-1 chains were rapidly degraded. <a href="#49" class="mim-tip-reference" title="Prockop, D. J. &lt;strong&gt;Osteogenesis imperfecta: phenotypic heterogeneity, protein suicide, short and long collagen.&lt;/strong&gt; Am. J. Hum. Genet. 36: 499-505, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6375355/&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;6375355&lt;/a&gt;]" pmid="6375355">Prockop (1984)</a> called this 'protein suicide.' In further studies <a href="#16" class="mim-tip-reference" title="Chu, M.-L., Gargiulo, V., Williams, C. J., Ramirez, F. &lt;strong&gt;Multiexon deletion in an osteogenesis imperfecta variant with increased type III collagen mRNA.&lt;/strong&gt; J. Biol. Chem. 260: 691-694, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2981843/&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;2981843&lt;/a&gt;]" pmid="2981843">Chu et al. (1985)</a> showed that the deletion eliminated 3 exons of the triple helical domain. The termini of the rearrangement were located within 2 short inverted repeats, suggesting that the self-complementary nature of these DNA elements favored formation of an intermediate that was the basis of the deletion. The patient's fibroblasts contained elevated type III collagen (<a href="/entry/120180">120180</a>) mRNA. The severity of the clinical presentation (with avulsion of the head and an arm during delivery) is explained. A null allele for pro-alpha-2 chains had much less deleterious effect (<a href="#25" class="mim-tip-reference" title="de Wet, W. J., Pihlajaniemi, T., Myers, J. C., Kelly, T. E., Prockop, D. J. &lt;strong&gt;Synthesis of a shortened pro-alpha-2(I) chain and decreased synthesis of pro-alpha-2(I) chains in a patient with osteogenesis imperfecta.&lt;/strong&gt; J. Biol. Chem. 258: 7721-7727, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6863261/&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;6863261&lt;/a&gt;]" pmid="6863261">de Wet et al., 1983</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6863261+6375355+1146889+2981843+6304100+6191221+1054840" 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="#61" class="mim-tip-reference" title="Steinmann, B., Rao, V. H., Vogel, A., Gitzelmann, R., Byers, P. H. &lt;strong&gt;A new structural mutation in the alpha-1(I) collagen chain from a patient with type II osteogenesis imperfecta (OI). (Abstract)&lt;/strong&gt; Europ. J. Pediat. 139: 317, 1982."None>Steinmann et al. (1982)</a> and <a href="#60" class="mim-tip-reference" title="Steinmann, B., Rao, V. H., Vogel, A., Bruckner, P., Gitzelmann, R., Byers, P. H. &lt;strong&gt;Cysteine in the triple-helical domain of one allelic product of the alpha-1(I) gene of type I collagen produces a lethal form of osteogenesis imperfecta.&lt;/strong&gt; J. Biol. Chem. 259: 11129-11138, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6469997/&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;6469997&lt;/a&gt;]" pmid="6469997">Steinmann et al. (1984)</a> studied material from a male newborn with the lethal perinatal form of OI (and avulsion of an arm). The mother had the Marfan syndrome, as did several other members of the kindred including 2 sibs of the OI proband. The father was healthy and young. The infant's dermis was thinner and collagen fibrils were smaller in diameter than normal and fibroblasts showed dilated endoplasmic reticulum filled with granular material. Cultured fibroblasts synthesized 2 different species of pro-alpha-1(I) chains in about equal amounts. One chain was normal; the other contained cysteine in the triple-helical portion of the COOH-terminal cyanogen bromide peptide alpha-1(I)CB6. Collagen molecules that contained 2 copies of the mutant chain formed alpha-1(I)-dimers linked through interchain disulfide bonds. Molecules containing either 1 or 2 mutant chains were delayed in secretion and underwent excessive posttranslational modification with resulting increased lysyl hydroxylation and hydroxylysyl glycosylation. Delay in triple-helix formation seemed to be responsible for the increased modification. Neither parent had a demonstrable abnormality of collagen. The authors suspected a point mutation with substitution of cysteine for glycine. This may have been the first known example of a point mutation in a collagen gene (<a href="#63" class="mim-tip-reference" title="Steinmann, B. &lt;strong&gt;Personal Communication.&lt;/strong&gt; Zurich, Switzerland 12/19/1983."None>Steinmann, 1983</a>). The role of the mother's Marfan syndrome is unclear; the molecular defect underlying the Marfan syndrome in this family had not been determined and it was not known whether the infant inherited the Marfan gene from the mother. The triple-helical domain of type I collagen contains no cysteine. It is made up of repeating triplets of amino acids Gly-X-Y where X and Y are any amino acid except tryptophan, tyrosine, and cysteine and most commonly proline and hydroxyproline, respectively. The fact that type III collagen contains cysteine (and tyrosine) in its triple-helical domain may indicate that its substitution for X or Y in type I collagen would not have as disruptive effects as observed here. In the lethal case thought by <a href="#60" class="mim-tip-reference" title="Steinmann, B., Rao, V. H., Vogel, A., Bruckner, P., Gitzelmann, R., Byers, P. H. &lt;strong&gt;Cysteine in the triple-helical domain of one allelic product of the alpha-1(I) gene of type I collagen produces a lethal form of osteogenesis imperfecta.&lt;/strong&gt; J. Biol. Chem. 259: 11129-11138, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6469997/&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;6469997&lt;/a&gt;]" pmid="6469997">Steinmann et al. (1984)</a> to represent a point mutation, <a href="#18" class="mim-tip-reference" title="Cohn, D. H., Byers, P. H., Steinmann, B., Gelinas, R. E. &lt;strong&gt;Lethal osteogenesis imperfecta resulting from a single nucleotide change in one human pro-alpha-1(I) collagen allele.&lt;/strong&gt; Proc. Nat. Acad. Sci. 83: 6045-6047, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3016737/&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;3016737&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.83.16.6045&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="3016737">Cohn et al. (1986)</a> indeed found substitution of cysteine for glycine at position 988 of the triple-helical portion of half of the alpha-1(I) chains of type I collagen (<a href="/entry/120150#0018">120150.0018</a>). The mutation disrupted the (G-X-Y)n pattern necessary for formation of the triple helix. This experiment of nature established the minimal mutation capable of producing lethal disease, and the lethality indicated the selective mechanism for stringent maintenance of collagen gene structure. A possibly high mutation rate for the OI II phenotype, which may be at least as frequent as 1 in 60,000 births, can be explained, even if most of them are dominants of the type described here. The COL1A1 gene may present a large target for lethal mutations because any change in the first 2 positions of the repeated GGN-NNN-NNN nucleotide sequence that encodes the triple-helical tripeptide Gly-X-Y is likely to be lethal if it occurs in the part of the gene encoding the carboxy-terminal half of the triple helix. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3016737+6469997" 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>Since the substitution of cysteine for glycine at position 988 of COL1A1 (<a href="/entry/120150#0018">120150.0018</a>) was in the critical first position of the G-X-Y triplet, the mutation in the heterozygous state caused a lethal clinical picture. Sequence data confirmed that the mutation was a single base G-to-T change (<a href="#18" class="mim-tip-reference" title="Cohn, D. H., Byers, P. H., Steinmann, B., Gelinas, R. E. &lt;strong&gt;Lethal osteogenesis imperfecta resulting from a single nucleotide change in one human pro-alpha-1(I) collagen allele.&lt;/strong&gt; Proc. Nat. Acad. Sci. 83: 6045-6047, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3016737/&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;3016737&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.83.16.6045&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="3016737">Cohn et al., 1986</a>). Conversely, <a href="#59" class="mim-tip-reference" title="Steinmann, B., Nicholls, A., Pope, F. M. &lt;strong&gt;Clinical variability of osteogenesis imperfecta reflecting molecular heterogeneity: cysteine substitutions in the alpha-1(I) collagen chain producing lethal and mild forms.&lt;/strong&gt; J. Biol. Chem. 261: 8958-8964, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3722184/&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;3722184&lt;/a&gt;]" pmid="3722184">Steinmann et al. (1986)</a> found that the substitution of cysteine in the same domain of the alpha-1 chain in another family resulted in mild autosomal dominant OI (<a href="/entry/166200">166200</a>). The difference resulted from the fact that the substitution of cysteine was for X or Y rather than for G in the G-X-Y triplet. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3016737+3722184" 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="#7" class="mim-tip-reference" title="Bodian, D. L., Chan, T.-F., Poon, A., Schwarze, U., Yang, K., Byers, P. H., Kwok, P.-Y., Klein, T. E. &lt;strong&gt;Mutation and polymorphism spectrum in osteogenesis imperfecta type II: implications for genotype-phenotype relationships.&lt;/strong&gt; Hum. Molec. Genet. 18: 463-471, 2009. Note: Erratum: Hum. Molec. Genet. 18: 1893-1895, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18996919/&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;18996919&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddn374&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="18996919">Bodian et al. (2009)</a> screened DNA samples from 62 unrelated individuals with the perinatal lethal form of OI and identified COL1A1 or COL1A2 mutations in 59 samples and CRTAP or LEPRE1 (<a href="/entry/610339">610339</a>) mutations in 3 samples. The authors identified 61 distinct heterozygous mutations in the COL1A1 and COL1A2 genes, including 5 nonsynonymous rare variants of unknown significance. Sixty SNPs in the COL1A1 gene (including 17 novel variants) and 82 SNPs in COL1A2 (including 18 novel variants) were reported. Their findings suggested a frequency of 5% for CRTAP and LEPRE1 recessive mutations in severe/lethal OI. A computer model for predicting the outcome of glycine substitutions within the triple-helical domain of COL1A1 chains predicted lethality with 90% accuracy (26 of 29 mutations). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18996919" 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="#65" class="mim-tip-reference" title="Takagi, M., Hori, N., Chinen, Y., Kurosawa, K., Tanaka, Y., Oku, K., Sakata, H., Fukuzawa, R., Nishimura, G., Spranger, J., Hasegawa, T. &lt;strong&gt;Heterozygous C-propeptide mutations in COL1A1: osteogenesis imperfecta type IIC and dense bone variant.&lt;/strong&gt; Am. J. Med. Genet. 155A: 2269-2273, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21834035/&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;21834035&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.34152&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="21834035">Takagi et al. (2011)</a> studied 4 Japanese patients, including 2 unrelated patients with what the authors called 'classic OI IIC' (see HISTORY) and 2 sibs with features of 'OI IIC' but less distortion of the tubular bones (OI dense bone variant). No consanguinity was reported in their parents. In both sibs and 1 sporadic patient, they identified heterozygous mutations in the C-propeptide region of COL1A1 (<a href="/entry/120150#0069">120150.0069</a> and <a href="/entry/120150#0070">120150.0070</a>, respectively), whereas no mutation in this region was identified in the other sporadic patient. Familial gene analysis revealed somatic mosaicism of the mutation in the clinically unaffected father of the sibs, whereas their mother and healthy older sister did not have the mutation. Histologic examination in the 2 sporadic cases showed a network of broad, interconnected cartilaginous trabeculae with thin osseous seams in the metaphyseal spongiosa. Thick, cartilaginous trabeculae (cartilaginous cores) were also found in the diaphyseal spongiosa. Chondrocyte columnization appeared somewhat irregular. These changes differed from the narrow and short metaphyseal trabeculae found in other lethal or severe cases of OI. <a href="#65" class="mim-tip-reference" title="Takagi, M., Hori, N., Chinen, Y., Kurosawa, K., Tanaka, Y., Oku, K., Sakata, H., Fukuzawa, R., Nishimura, G., Spranger, J., Hasegawa, T. &lt;strong&gt;Heterozygous C-propeptide mutations in COL1A1: osteogenesis imperfecta type IIC and dense bone variant.&lt;/strong&gt; Am. J. Med. Genet. 155A: 2269-2273, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21834035/&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;21834035&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.34152&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="21834035">Takagi et al. (2011)</a> concluded that heterozygous C-propeptide mutations in the COL1A1 gene may result in OI IIC with or without twisting of the long bones and that OI IIC appears to be inherited as an autosomal dominant trait. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21834035" 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="nomenclature" class="mim-anchor"></a>
<h4 href="#mimNomenclatureFold" id="mimNomenclatureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimNomenclatureToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Nomenclature</strong>
</span>
</h4>
</div>
<div id="mimNomenclatureFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>The autosomal recessive form of lethal OI designated OI VII (<a href="/entry/610682">610682</a>) had previously been designated OI IIB (OI2B). For a short time, the autosomal dominant form of lethal OI (OI II; OI2) was designated OI IIA (OI2A).</p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="history" class="mim-anchor"></a>
<h4 href="#mimHistoryFold" id="mimHistoryToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimHistoryToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>History</strong>
</span>
</h4>
</div>
<div id="mimHistoryFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#54" class="mim-tip-reference" title="Sillence, D. O., Barlow, K. K., Garber, A. P., Hall, J. G., Rimoin, D. L. &lt;strong&gt;Osteogenesis imperfecta type II: delineation of the phenotype with reference to genetic heterogeneity.&lt;/strong&gt; Am. J. Med. Genet. 17: 407-423, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6702894/&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;6702894&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320170204&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="6702894">Sillence et al. (1984)</a> reviewed 48 cases of the perinatal lethal form of OI (OI type II) and subclassified them into 3 categories on the basis of radiologic features: group A (38 cases)--short, broad, 'crumpled' long bones, angulation of tibias and continuously beaded ribs; group B (6 cases)--short, broad, crumpled femurs, angulation of tibias but normal ribs or ribs with incomplete beading; and group C (4 cases)--long, thin, inadequately modeled long bones with multiple fractures and thin beaded ribs. Information for segregation analysis was available on 33 families. Two or more sibs were affected in 6 of the families; 3 of these 6 families were examined by the authors and found to fall into group A, 2 into group B, and 1 into group C. The parents were related in 1 family of type A and 1 family of type C. Mean paternal age was not increased. For all these reasons, <a href="#54" class="mim-tip-reference" title="Sillence, D. O., Barlow, K. K., Garber, A. P., Hall, J. G., Rimoin, D. L. &lt;strong&gt;Osteogenesis imperfecta type II: delineation of the phenotype with reference to genetic heterogeneity.&lt;/strong&gt; Am. J. Med. Genet. 17: 407-423, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6702894/&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;6702894&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320170204&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="6702894">Sillence et al. (1984)</a> concluded that most cases of OI II represent an autosomal recessive disorder. There is, however, clearly an autosomal dominant form as indicated by biochemical evidence provided by the studies of <a href="#4" class="mim-tip-reference" title="Barsh, G. S., Byers, P. H. &lt;strong&gt;Reduced secretion of structurally abnormal type I procollagen in a form of osteogenesis imperfecta.&lt;/strong&gt; Proc. Nat. Acad. Sci. 78: 5142-5146, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6946461/&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;6946461&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.78.8.5142&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="6946461">Barsh and Byers (1981)</a> that there are 2 types of collagen I alpha-1 chains synthesized by fibroblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6946461+6702894" 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>Commenting on the paper of <a href="#54" class="mim-tip-reference" title="Sillence, D. O., Barlow, K. K., Garber, A. P., Hall, J. G., Rimoin, D. L. &lt;strong&gt;Osteogenesis imperfecta type II: delineation of the phenotype with reference to genetic heterogeneity.&lt;/strong&gt; Am. J. Med. Genet. 17: 407-423, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6702894/&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;6702894&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320170204&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="6702894">Sillence et al. (1984)</a>, <a href="#57" class="mim-tip-reference" title="Spranger, J. &lt;strong&gt;Osteogenesis imperfecta: a pasture for splitters and lumpers. (Editorial)&lt;/strong&gt; Am. J. Med. Genet. 17: 425-428, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6702895/&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;6702895&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320170205&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="6702895">Spranger (1984)</a> stated that 'Type IIC poses no major nosologic problems' because of the radiologic distinctiveness. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6702895+6702894" 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>On radiographic grounds, <a href="#68" class="mim-tip-reference" title="Tsipouras, P., Bonadio, J. F., Schwartz, R. C., Horwitz, A., Byers, P. H. &lt;strong&gt;Osteogenesis imperfecta type II is usually due to new dominant mutations. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 37: A79, 1985."None>Tsipouras et al. (1985)</a> suggested that 5 types of type II OI could be distinguished. Five patients in 3 families appeared to have type 5, the least severe form. The parents of these 5 patients were consanguineous, and <a href="#68" class="mim-tip-reference" title="Tsipouras, P., Bonadio, J. F., Schwartz, R. C., Horwitz, A., Byers, P. H. &lt;strong&gt;Osteogenesis imperfecta type II is usually due to new dominant mutations. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 37: A79, 1985."None>Tsipouras et al. (1985)</a> suggested that the inheritance of type 5 may be autosomal recessive.</p>
</span>
<div>
<br />
</div>
</div>
<div>
<a id="heterogeneity" class="mim-anchor"></a>
<h4 href="#mimHeterogeneityFold" id="mimHeterogeneityToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimHeterogeneityToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Heterogeneity</strong>
</span>
</h4>
</div>
<div id="mimHeterogeneityFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p><a href="#1" class="mim-tip-reference" title="Aitchison, K., Ogilvie, D., Honeyman, M., Thompson, E., Sykes, B. &lt;strong&gt;Homozygous osteogenesis imperfecta unlinked to collagen I genes.&lt;/strong&gt; Hum. Genet. 78: 233-236, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2894346/&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;2894346&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00291667&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="2894346">Aitchison et al. (1988)</a> studied a child with type II OI of Sillence subclassification B who was the product of consanguineous Pakistani parents. A brother and sister of the proband's mother, also the product of a consanguineous mating, had died with OI in the perinatal period. The proband was heterozygous for COL1A1 and COL1A2 genotypes, suggesting that the mutation causing the disease in this child was not at either of the structural genes for type I collagen. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2894346" 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="#58" class="mim-tip-reference" title="Stacey, A., Bateman, J., Choi, T., Mascara, T., Cole, W., Jaenisch, R. &lt;strong&gt;Perinatal lethal osteogenesis imperfecta in transgenic mice bearing an engineered mutant pro-alpha-1(I) collagen gene.&lt;/strong&gt; Nature 332: 131-136, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2450280/&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;2450280&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/332131a0&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="2450280">Stacey et al. (1988)</a> reproduced the OI II phenotype in transgenic mice carrying a mutant alpha-1(I) collagen gene into which specific glycine substitutions had been engineered. The experiments reproduced the findings in patients in whom a single point mutation resulted in OIC: substitution of glycine by arginine at position 391 (<a href="#5" class="mim-tip-reference" title="Bateman, J. F., Chan, D., Walker, I. D., Rogers, J. G., Cole, W. G. &lt;strong&gt;Lethal perinatal osteogenesis imperfecta due to the substitution of arginine for glycine at residue 391 of the alpha-1(I) chain of type I collagen.&lt;/strong&gt; J. Biol. Chem. 262: 7021-7027, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3108247/&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;3108247&lt;/a&gt;]" pmid="3108247">Bateman et al., 1987</a>) or substitution of glycine by cysteine at position 988 (<a href="#18" class="mim-tip-reference" title="Cohn, D. H., Byers, P. H., Steinmann, B., Gelinas, R. E. &lt;strong&gt;Lethal osteogenesis imperfecta resulting from a single nucleotide change in one human pro-alpha-1(I) collagen allele.&lt;/strong&gt; Proc. Nat. Acad. Sci. 83: 6045-6047, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3016737/&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;3016737&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.83.16.6045&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="3016737">Cohn et al., 1986</a>). <a href="#22" class="mim-tip-reference" title="Constantinou, C. D., Nielsen, K. B., Prockop, D. J. &lt;strong&gt;A lethal variant of osteogenesis imperfecta has a single base mutation that substitutes cysteine for glycine 904 of the alpha-1(I) chain of type I procollagen: the asymptomatic mother has an unidentified mutation producing an overmodified and unstable type I procollagen.&lt;/strong&gt; J. Clin. Invest. 83: 574-584, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2913053/&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;2913053&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI113920&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="2913053">Constantinou et al. (1989)</a> described a lethal variant of OI in which a G-to-T substitution converted glycine to cysteine at position 904 of the COL1A1 gene. In addition, the proband may have inherited a second mutation from her asymptomatic mother that produced an overmodified and thermally unstable species of type I procollagen. Her mother was somewhat short and had slightly blue sclerae. <a href="#40" class="mim-tip-reference" title="Lamande, S. R., Dahl, H.-H. M., Cole, W. G., Bateman, J. F. &lt;strong&gt;Characterization of point mutations in the collagen COL1A1 and COL1A2 genes causing lethal perinatal osteogenesis imperfecta.&lt;/strong&gt; J. Biol. Chem. 264: 15809-15812, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2777764/&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;2777764&lt;/a&gt;]" pmid="2777764">Lamande et al. (1989)</a> used the method of <a href="#23" class="mim-tip-reference" title="Cotton, R. G. H., Rodrigues, N. R., Campbell, R. D. &lt;strong&gt;Reactivity of cytosine and thymine in single-base-pair mismatches with hydroxylamine and osmium tetroxide and its application to the study of mutations.&lt;/strong&gt; Proc. Nat. Acad. Sci. 85: 4397-4401, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3260032/&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;3260032&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.85.12.4397&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="3260032">Cotton et al. (1988)</a> to identify single base changes in the subunits of type I collagen in 5 patients with OIC. In 4 cases, the substitution was found in the alpha-1 subunit, and in 1 it was located in the alpha-2 chain. In all 5 cases, the first glycine in the amino acid triplet was replaced: gly-973 and gly-1006 to val, gly-928 to ala, and gly-976 to arg in the alpha-1 chain and gly-865 to ser in the alpha-2 chain. These mutations emphasize the importance of the Gly-X-Y repeating amino acid triplet for normal collagen helix formation and function. The method of <a href="#23" class="mim-tip-reference" title="Cotton, R. G. H., Rodrigues, N. R., Campbell, R. D. &lt;strong&gt;Reactivity of cytosine and thymine in single-base-pair mismatches with hydroxylamine and osmium tetroxide and its application to the study of mutations.&lt;/strong&gt; Proc. Nat. Acad. Sci. 85: 4397-4401, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3260032/&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;3260032&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.85.12.4397&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="3260032">Cotton et al. (1988)</a> exploits the increased chemical modification of cytosines by hydroxylamine and of thymines by osmium tetroxide, when they are not paired with their complementary base. The DNA chain is then cleaved at the modified bases with piperidine. The use of radioactively end-labeled DNA probes allows the position of the mismatched cytosines and thymines in the probe to be determined by electrophoresis of the cleavage products. <a href="#21" class="mim-tip-reference" title="Cole, W. G., Patterson, E., Bonadio, J., Campbell, P. E., Fortune, D. W. &lt;strong&gt;The clinicopathological features of three babies with osteogenesis imperfecta resulting from the substitution of glycine by valine in the pro-alpha-1(I) chain of type I procollagen.&lt;/strong&gt; J. Med. Genet. 29: 112-118, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1613761/&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;1613761&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.29.2.112&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="1613761">Cole et al. (1992)</a> described the occurrence of premature birth in OIC due to precocious rupture of membranes and antepartum hemorrhage. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3108247+1613761+3260032+2913053+3016737+2450280+2777764" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
</span>
<div>
<br />
</div>
</div>
</div>
<div>
<a id="seeAlso" class="mim-anchor"></a>
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span class="mim-font">
<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>See Also:</strong>
</span>
</h4>
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<a href="#Bateman1984" class="mim-tip-reference" title="Bateman, J. F., Mascara, T., Chan, D., Cole, W. G. &lt;strong&gt;Abnormal type I collagen metabolism by cultured fibroblasts in lethal perinatal osteogenesis imperfecta.&lt;/strong&gt; Biochem. J. 217: 103-115, 1984.">Bateman et al. (1984)</a>; <a href="#Braga1981" class="mim-tip-reference" title="Braga, S., Passarge, E. &lt;strong&gt;Congenital osteogenesis imperfecta in three sibs.&lt;/strong&gt; Hum. Genet. 58: 441-443, 1981.">Braga and Passarge (1981)</a>; <a href="#Goldfarb1954" class="mim-tip-reference" title="Goldfarb, A. A., Ford, D., Jr. &lt;strong&gt;Osteogenesis imperfecta congenita in consecutive siblings.&lt;/strong&gt; J. Pediat. 44: 264-268, 1954.">Goldfarb and Ford
(1954)</a>; <a href="#Goldman1980" class="mim-tip-reference" title="Goldman, A. B., Davidson, D., Pavlov, H., Bullough, P. G. &lt;strong&gt;&#x27;Popcorn&#x27; calcifications: a prognostic sign in osteogenesis imperfecta.&lt;/strong&gt; Radiology 136: 351-358, 1980.">Goldman et al. (1980)</a>; <a href="#Horan1975" class="mim-tip-reference" title="Horan, F., Beighton, P. &lt;strong&gt;Autosomal recessive inheritance of osteogenesis imperfecta.&lt;/strong&gt; Clin. Genet. 8: 107-111, 1975.">Horan and Beighton (1975)</a>; <a href="#Ibsen1967" class="mim-tip-reference" title="Ibsen, K. H. &lt;strong&gt;Distinct varieties of osteogenesis imperfecta.&lt;/strong&gt; Clin. Orthop. 50: 279-290, 1967.">Ibsen
(1967)</a>; <a href="#Pihlajaniemi1984" class="mim-tip-reference" title="Pihlajaniemi, T., Dickson, L. A., Pope, F. M., Korhonen, V. M., Nicholls, A., Prockop, D. J., Myers, J. C. &lt;strong&gt;Osteogenesis imperfecta: cloning of a pro-alpha-2(I) collagen gene with a frameshift mutation.&lt;/strong&gt; J. Biol. Chem. 259: 12941-12944, 1984.">Pihlajaniemi et al. (1984)</a>; <a href="#Schroder1964" class="mim-tip-reference" title="Schroder, G. &lt;strong&gt;Eine klinisch-erbbiologische Untersuchung des Krankengutes in Westfalen. Schaetzung der Mutationsraten fuer den Regierungsbezirk Munster (Westfalen).&lt;/strong&gt; Z. Menschl. Vererb. Konstitutionsl. 37: 632-676, 1964.">Schroder (1964)</a>; <a href="#Stephens1983" class="mim-tip-reference" title="Stephens, J. D., Filly, R. A., Callen, P. W., Golbus, M. S. &lt;strong&gt;Prenatal diagnosis of osteogenesis imperfecta type II by real-time ultrasound.&lt;/strong&gt; Hum. Genet. 64: 191-193, 1983.">Stephens et al.
(1983)</a>; <a href="#Wilson1974" class="mim-tip-reference" title="Wilson, M. G. &lt;strong&gt;Congenital osteogenesis imperfecta.In: Bergsma, D. : Skeletal Dysplasias.&lt;/strong&gt; Amsterdam: Excerpta Medica (pub.) 1974. Pp. 296-298.">Wilson (1974)</a>; <a href="#Zeitoun1963" class="mim-tip-reference" title="Zeitoun, M. M., Ibrahim, A. H., Kassem, A. S. &lt;strong&gt;Osteogenesis imperfecta congenita in dizygotic twins.&lt;/strong&gt; Arch. Dis. Child. 38: 289-291, 1963.">Zeitoun et al. (1963)</a>
</span>
<div>
<br />
</div>
</div>
</div>
<div>
<a id="references"class="mim-anchor"></a>
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span class="mim-font">
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">&#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="Aitchison1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Aitchison, K., Ogilvie, D., Honeyman, M., Thompson, E., Sykes, B.
<strong>Homozygous osteogenesis imperfecta unlinked to collagen I genes.</strong>
Hum. Genet. 78: 233-236, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2894346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2894346</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2894346" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF00291667" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="2" class="mim-anchor"></a>
<a id="Awwaad1960" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Awwaad, S., Reda, M.
<strong>Osteogenesis imperfecta: review of literature and a report on three cases.</strong>
Arch. Pediat. 77: 280-290, 1960.
</p>
</div>
</li>
<li>
<a id="3" class="mim-anchor"></a>
<a id="Barnes2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Barnes, A. M., Chang, W., Morello, R., Cabral, W. A., Weis, M., Eyre, D. R., Leikin, S., Makareeva, E., Kuznetsova, N., Uveges, T. E., Ashok, A., Flor, A. W., Mulvihill, J. J., Wilson, P. L., Sundaram, U. T., Lee, B., Marini, J. C.
<strong>Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta.</strong>
New Eng. J. Med. 355: 2757-2764, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17192541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17192541</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17192541[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=17192541" 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/NEJMoa063804" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="4" class="mim-anchor"></a>
<a id="Barsh1981" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Barsh, G. S., Byers, P. H.
<strong>Reduced secretion of structurally abnormal type I procollagen in a form of osteogenesis imperfecta.</strong>
Proc. Nat. Acad. Sci. 78: 5142-5146, 1981.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6946461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6946461</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6946461" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.78.8.5142" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="5" class="mim-anchor"></a>
<a id="Bateman1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bateman, J. F., Chan, D., Walker, I. D., Rogers, J. G., Cole, W. G.
<strong>Lethal perinatal osteogenesis imperfecta due to the substitution of arginine for glycine at residue 391 of the alpha-1(I) chain of type I collagen.</strong>
J. Biol. Chem. 262: 7021-7027, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3108247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3108247</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3108247" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="6" class="mim-anchor"></a>
<a id="Bateman1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bateman, J. F., Mascara, T., Chan, D., Cole, W. G.
<strong>Abnormal type I collagen metabolism by cultured fibroblasts in lethal perinatal osteogenesis imperfecta.</strong>
Biochem. J. 217: 103-115, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6421277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6421277</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6421277" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1042/bj2170103" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="7" class="mim-anchor"></a>
<a id="Bodian2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bodian, D. L., Chan, T.-F., Poon, A., Schwarze, U., Yang, K., Byers, P. H., Kwok, P.-Y., Klein, T. E.
<strong>Mutation and polymorphism spectrum in osteogenesis imperfecta type II: implications for genotype-phenotype relationships.</strong>
Hum. Molec. Genet. 18: 463-471, 2009. Note: Erratum: Hum. Molec. Genet. 18: 1893-1895, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18996919/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18996919</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18996919" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/ddn374" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="8" class="mim-anchor"></a>
<a id="Bonadio1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bonadio, J., Ramirez, F., Barr, M.
<strong>An intron mutation in the human alpha-1(I) collagen gene alters the efficiency of pre-mRNA splicing and is associated with osteogenesis imperfecta type II.</strong>
J. Biol. Chem. 265: 2262-2268, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2298750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2298750</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2298750" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="9" class="mim-anchor"></a>
<a id="Bonadio1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bonadio, J.
<strong>Personal Communication.</strong>
Ann Arbor, Mich. 3/1990.
</p>
</div>
</li>
<li>
<a id="10" class="mim-anchor"></a>
<a id="Bonadio1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bonadio, J.
<strong>Personal Communication.</strong>
Ann Arbor, Mich. 2/7/1992.
</p>
</div>
</li>
<li>
<a id="11" class="mim-anchor"></a>
<a id="Braga1981" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Braga, S., Passarge, E.
<strong>Congenital osteogenesis imperfecta in three sibs.</strong>
Hum. Genet. 58: 441-443, 1981.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7327569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7327569</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7327569" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF00282834" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="12" class="mim-anchor"></a>
<a id="Buyse1978" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Buyse, M., Bull, M. J.
<strong>A syndrome of osteogenesis imperfecta, microcephaly, and cataracts.</strong>
Birth Defects Orig. Art. Ser. XIV(6B): 95-98, 1978.
</p>
</div>
</li>
<li>
<a id="13" class="mim-anchor"></a>
<a id="Byers1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Byers, P. H., Bonadio, J. F., Steinmann, B.
<strong>Osteogenesis imperfecta: update and perspective. (Editorial)</strong>
Am. J. Med. Genet. 17: 429-435, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6702896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6702896</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6702896" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320170206" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="14" class="mim-anchor"></a>
<a id="Byers2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Byers, P. H., Krakow, D., Nunes, M. E., Pepin, M.
<strong>Genetic evaluation of suspected osteogenesis imperfecta (OI).</strong>
Genet. Med. 8: 383-388, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16778601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16778601</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16778601" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1097/01.gim.0000223557.54670.aa" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="15" class="mim-anchor"></a>
<a id="Byers1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Byers, P. H., Tsipouras, P., Bonadio, J. F., Starman, B. J., Schwartz, R. C.
<strong>Perinatal lethal osteogenesis imperfecta (OI type II): a biochemically heterogeneous disorder usually due to new mutations in the genes for type I collagen.</strong>
Am. J. Hum. Genet. 42: 237-248, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3341380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3341380</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3341380" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="16" class="mim-anchor"></a>
<a id="Chu1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Chu, M.-L., Gargiulo, V., Williams, C. J., Ramirez, F.
<strong>Multiexon deletion in an osteogenesis imperfecta variant with increased type III collagen mRNA.</strong>
J. Biol. Chem. 260: 691-694, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2981843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2981843</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2981843" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="17" class="mim-anchor"></a>
<a id="Chu1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Chu, M.-L., Williams, C. J., Pepe, G., Hirsch, J. L., Prockop, D. J., Ramirez, F.
<strong>Internal deletion in a collagen gene in a perinatal lethal form of osteogenesis imperfecta.</strong>
Nature 304: 78-80, 1983.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6191221/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6191221</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6191221" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/304078a0" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="18" class="mim-anchor"></a>
<a id="Cohn1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Cohn, D. H., Byers, P. H., Steinmann, B., Gelinas, R. E.
<strong>Lethal osteogenesis imperfecta resulting from a single nucleotide change in one human pro-alpha-1(I) collagen allele.</strong>
Proc. Nat. Acad. Sci. 83: 6045-6047, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3016737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3016737</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3016737" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.83.16.6045" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="19" class="mim-anchor"></a>
<a id="Cohn1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Cohn, D. H., Starman, B. J., Blumberg, B., Byers, P. H.
<strong>Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a dominant mutation in a human type I collagen gene (COL1A1).</strong>
Am. J. Hum. Genet. 46: 591-601, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2309707/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2309707</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2309707" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="20" class="mim-anchor"></a>
<a id="Cole1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Cole, W. G., Dalgleish, R.
<strong>Perinatal lethal osteogenesis imperfecta.</strong>
J. Med. Genet. 32: 284-289, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7643358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7643358</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7643358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.32.4.284" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="21" class="mim-anchor"></a>
<a id="Cole1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Cole, W. G., Patterson, E., Bonadio, J., Campbell, P. E., Fortune, D. W.
<strong>The clinicopathological features of three babies with osteogenesis imperfecta resulting from the substitution of glycine by valine in the pro-alpha-1(I) chain of type I procollagen.</strong>
J. Med. Genet. 29: 112-118, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1613761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1613761</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1613761" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.29.2.112" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="22" class="mim-anchor"></a>
<a id="Constantinou1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Constantinou, C. D., Nielsen, K. B., Prockop, D. J.
<strong>A lethal variant of osteogenesis imperfecta has a single base mutation that substitutes cysteine for glycine 904 of the alpha-1(I) chain of type I procollagen: the asymptomatic mother has an unidentified mutation producing an overmodified and unstable type I procollagen.</strong>
J. Clin. Invest. 83: 574-584, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2913053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2913053</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2913053" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1172/JCI113920" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="23" class="mim-anchor"></a>
<a id="Cotton1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Cotton, R. G. H., Rodrigues, N. R., Campbell, R. D.
<strong>Reactivity of cytosine and thymine in single-base-pair mismatches with hydroxylamine and osmium tetroxide and its application to the study of mutations.</strong>
Proc. Nat. Acad. Sci. 85: 4397-4401, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3260032/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3260032</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3260032" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.85.12.4397" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="24" class="mim-anchor"></a>
<a id="Daw1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Daw, S. C. M., Gibbs, D. A., Nicholls, A. C., Hall, E. C., Siggers, D. C., Pope, F. M.
<strong>Lethal osteogenesis imperfecta: a family with 6 affected sibs heterozygous for a type I collagen mutation. (Abstract)</strong>
J. Med. Genet. 27: 206, 1990.
</p>
</div>
</li>
<li>
<a id="25" class="mim-anchor"></a>
<a id="de Wet1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
de Wet, W. J., Pihlajaniemi, T., Myers, J. C., Kelly, T. E., Prockop, D. J.
<strong>Synthesis of a shortened pro-alpha-2(I) chain and decreased synthesis of pro-alpha-2(I) chains in a patient with osteogenesis imperfecta.</strong>
J. Biol. Chem. 258: 7721-7727, 1983.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6863261/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6863261</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6863261" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="26" class="mim-anchor"></a>
<a id="Delvin1979" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Delvin, E. E., Glorieux, F. H., Lopez, E.
<strong>In vitro sulfate turnover in osteogenesis imperfecta congenita and tarda.</strong>
Am. J. Med. Genet. 4: 349-355, 1979.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/539603/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">539603</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=539603" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320040406" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="27" class="mim-anchor"></a>
<a id="Edwards1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Edwards, M. J., Wenstrup, R. J., Byers, P. H., Cohn, D. H.
<strong>Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a mutation in the COL1A2 gene of type I collagen: the mosaic parent exhibits phenotypic features of a mild form of the disease.</strong>
Hum. Mutat. 1: 47-54, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301191</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301191" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/humu.1380010108" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="28" class="mim-anchor"></a>
<a id="Elejalde1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Elejalde, B. R., de Elejalde, M. M.
<strong>Prenatal diagnosis of perinatally lethal osteogenesis imperfecta.</strong>
Am. J. Med. Genet. 14: 353-359, 1983.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6837630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6837630</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6837630" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320140215" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="29" class="mim-anchor"></a>
<a id="Francis1981" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Francis, M. J. O., Williams, K. J., Sykes, B. C., Smith, R.
<strong>The relative amounts of the collagen chains alpha-1(I), alpha-2 and alpha-1(III) in the skin of 31 patients with osteogenesis imperfecta.</strong>
Clin. Sci. (Lond.) 60: 617-623, 1981.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6788428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6788428</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6788428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1042/cs0600617" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="30" class="mim-anchor"></a>
<a id="Freund1954" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Freund, R., Lehmacher, K.
<strong>Beitrag zur Vererbung der Osteogenesis imperfecta.</strong>
Geburtsh. Frauenheilk. 14: 171-177, 1954.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13151389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13151389</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13151389" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="31" class="mim-anchor"></a>
<a id="Goldfarb1954" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Goldfarb, A. A., Ford, D., Jr.
<strong>Osteogenesis imperfecta congenita in consecutive siblings.</strong>
J. Pediat. 44: 264-268, 1954.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13143452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13143452</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13143452" 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/s0022-3476(54)80315-5" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="32" class="mim-anchor"></a>
<a id="Goldman1980" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Goldman, A. B., Davidson, D., Pavlov, H., Bullough, P. G.
<strong>'Popcorn' calcifications: a prognostic sign in osteogenesis imperfecta.</strong>
Radiology 136: 351-358, 1980.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7403509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7403509</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7403509" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1148/radiology.136.2.7403509" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="33" class="mim-anchor"></a>
<a id="Hanhart1951" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hanhart, E.
<strong>Ueber eine neue Form von Osteopsathyrosis congenita mit einfach-rezessivem, sowie 4 neue Sippen mit dominantem Erbgang und die Frage der Vererbung der sog. Osteogenesis imperfecta.</strong>
Arch. Klaus Stift. Vererbungsforsch. 26: 426-437, 1951.
</p>
</div>
</li>
<li>
<a id="34" class="mim-anchor"></a>
<a id="Heller1975" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Heller, R. H., Winn, K. J., Heller, R. M.
<strong>The prenatal diagnosis of osteogenesis imperfecta congenita.</strong>
Am. J. Obstet. Gynec. 121: 572-573, 1975.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1146889/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1146889</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1146889" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0002-9378(75)90101-5" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="35" class="mim-anchor"></a>
<a id="Horan1975" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Horan, F., Beighton, P.
<strong>Autosomal recessive inheritance of osteogenesis imperfecta.</strong>
Clin. Genet. 8: 107-111, 1975.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1175315/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1175315</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1175315" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1399-0004.1975.tb04398.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="36" class="mim-anchor"></a>
<a id="Horwitz1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Horwitz, A. L., Lazda, V., Byers, P. H.
<strong>Recurrent type II (lethal) osteogenesis imperfecta: apparent dominant inheritance. (Abstract)</strong>
Am. J. Hum. Genet. 37: A59, 1985.
</p>
</div>
</li>
<li>
<a id="37" class="mim-anchor"></a>
<a id="Ibsen1967" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ibsen, K. H.
<strong>Distinct varieties of osteogenesis imperfecta.</strong>
Clin. Orthop. 50: 279-290, 1967.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5339474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5339474</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5339474" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="38" class="mim-anchor"></a>
<a id="Kaplan1953" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kaplan, M., Baldino, C.
<strong>Dysplasie periostale paraissant familiale et transmise suivant le mode Mendelien recessif.</strong>
Arch. Franc. Pediat. 10: 943-950, 1953.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13125648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13125648</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13125648" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="39" class="mim-anchor"></a>
<a id="Kaplan1958" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kaplan, M., Laplane, M. R., Debray, P., Lasfargues, G.
<strong>Sur l'heredite de la dysplasie periostale complement a la communication de M. Kaplan et C. Baldino.</strong>
Arch. Franc. Pediat. 15: 1097-1101, 1958.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13595987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13595987</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13595987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="40" class="mim-anchor"></a>
<a id="Lamande1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lamande, S. R., Dahl, H.-H. M., Cole, W. G., Bateman, J. F.
<strong>Characterization of point mutations in the collagen COL1A1 and COL1A2 genes causing lethal perinatal osteogenesis imperfecta.</strong>
J. Biol. Chem. 264: 15809-15812, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2777764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2777764</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2777764" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="41" class="mim-anchor"></a>
<a id="Laplane1959" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Laplane, M. R., Lasfargues, G., Debray, P.
<strong>Essai de classification genetique des osteogeneses imparfaites.</strong>
Presse Med. 67: 893-895, 1959.
</p>
</div>
</li>
<li>
<a id="42" class="mim-anchor"></a>
<a id="Levin1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Levin, L. S., Rosenbaum, K. N., Brady, J. M., Dorst, J. P.
<strong>Osteogenesis imperfecta lethal in infancy: case report and scanning electron microscopic studies of the deciduous teeth.</strong>
Am. J. Med. Genet. 13: 359-368, 1982.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7158636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7158636</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7158636" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320130403" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="43" class="mim-anchor"></a>
<a id="McKusick1962" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
McKusick, V. A.
<strong>Medical genetics 1961.</strong>
J. Chronic Dis. 15: 417-572, 1962. Fig. 50.
</p>
</div>
</li>
<li>
<a id="44" class="mim-anchor"></a>
<a id="McKusick1972" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
McKusick, V. A.
<strong>Heritable Disorders of Connective Tissue. (4th ed.)</strong>
St. Louis: C. V. Mosby (pub.) 1972.
</p>
</div>
</li>
<li>
<a id="45" class="mim-anchor"></a>
<a id="Meyer1955" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Meyer, H. J.
<strong>Atypical osteogenesis imperfecta: Lobstein's disease.</strong>
Arch. Pediat. 72: 182-186, 1955.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13249697/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13249697</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13249697" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="46" class="mim-anchor"></a>
<a id="Orioli1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Orioli, I. M., Castilla, E. E., Scarano, G., Mastroiacovo, P.
<strong>Effect of paternal age in achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta.</strong>
Am. J. Med. Genet. 59: 209-217, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8588588/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8588588</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8588588" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320590218" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="47" class="mim-anchor"></a>
<a id="Penttinen1975" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Penttinen, R. P., Lichtenstein, J. R., Martin, G. R., McKusick, V. A.
<strong>Abnormal collagen metabolism in cultured cells in osteogenesis imperfecta.</strong>
Proc. Nat. Acad. Sci. 72: 586-589, 1975.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1054840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1054840</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1054840" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.72.2.586" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="48" class="mim-anchor"></a>
<a id="Pihlajaniemi1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Pihlajaniemi, T., Dickson, L. A., Pope, F. M., Korhonen, V. M., Nicholls, A., Prockop, D. J., Myers, J. C.
<strong>Osteogenesis imperfecta: cloning of a pro-alpha-2(I) collagen gene with a frameshift mutation.</strong>
J. Biol. Chem. 259: 12941-12944, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6092353/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6092353</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6092353" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="49" class="mim-anchor"></a>
<a id="Prockop1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Prockop, D. J.
<strong>Osteogenesis imperfecta: phenotypic heterogeneity, protein suicide, short and long collagen.</strong>
Am. J. Hum. Genet. 36: 499-505, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6375355/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6375355</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6375355" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="50" class="mim-anchor"></a>
<a id="Remigio1970" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Remigio, P. A., Grinvalsky, H. T.
<strong>Osteogenesis imperfecta congenita: association with conspicuous extraskeletal connective tissue dysplasia.</strong>
Am. J. Dis. Child. 119: 524-528, 1970.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5443340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5443340</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5443340" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="51" class="mim-anchor"></a>
<a id="Rohwedder1953" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Rohwedder, H. J.
<strong>Ein Beitrag zur Frage des Erbganges der Osteogenesis imperfecta Vrolik.</strong>
Arch. Kinderheilk. 147: 256-262, 1953.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13139510/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13139510</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13139510" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="52" class="mim-anchor"></a>
<a id="Schroder1964" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Schroder, G.
<strong>Eine klinisch-erbbiologische Untersuchung des Krankengutes in Westfalen. Schaetzung der Mutationsraten fuer den Regierungsbezirk Munster (Westfalen).</strong>
Z. Menschl. Vererb. Konstitutionsl. 37: 632-676, 1964.
</p>
</div>
</li>
<li>
<a id="53" class="mim-anchor"></a>
<a id="Shapiro1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Shapiro, J. E., Phillips, J. A., Byers, P. H., Sanders, R., Holbrook, K. A., Levin, L. S., Dorst, J., Barsh, G. S., Peterson, K. E., Goldstein, P.
<strong>Prenatal diagnosis of lethal perinatal osteogenesis imperfecta (OI type II).</strong>
J. Pediat. 100: 127-133, 1982.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7057300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7057300</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7057300" 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/s0022-3476(82)80252-7" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="54" class="mim-anchor"></a>
<a id="Sillence1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Sillence, D. O., Barlow, K. K., Garber, A. P., Hall, J. G., Rimoin, D. L.
<strong>Osteogenesis imperfecta type II: delineation of the phenotype with reference to genetic heterogeneity.</strong>
Am. J. Med. Genet. 17: 407-423, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6702894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6702894</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6702894" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320170204" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="55" class="mim-anchor"></a>
<a id="Sillence1979" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Sillence, D. O., Senn, A., Danks, D. M.
<strong>Genetic heterogeneity in osteogenesis imperfecta.</strong>
J. Med. Genet. 16: 101-116, 1979.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/458828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">458828</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=458828" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.16.2.101" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="56" class="mim-anchor"></a>
<a id="Smars1961" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Smars, G., Beckman, L., Book, J. A.
<strong>Osteogenesis imperfecta and blood groups.</strong>
Acta Genet. Statist. Med. 11: 133-136, 1961.
</p>
</div>
</li>
<li>
<a id="57" class="mim-anchor"></a>
<a id="Spranger1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Spranger, J.
<strong>Osteogenesis imperfecta: a pasture for splitters and lumpers. (Editorial)</strong>
Am. J. Med. Genet. 17: 425-428, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6702895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6702895</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6702895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320170205" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="58" class="mim-anchor"></a>
<a id="Stacey1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Stacey, A., Bateman, J., Choi, T., Mascara, T., Cole, W., Jaenisch, R.
<strong>Perinatal lethal osteogenesis imperfecta in transgenic mice bearing an engineered mutant pro-alpha-1(I) collagen gene.</strong>
Nature 332: 131-136, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2450280/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2450280</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2450280" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/332131a0" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="59" class="mim-anchor"></a>
<a id="Steinmann1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Steinmann, B., Nicholls, A., Pope, F. M.
<strong>Clinical variability of osteogenesis imperfecta reflecting molecular heterogeneity: cysteine substitutions in the alpha-1(I) collagen chain producing lethal and mild forms.</strong>
J. Biol. Chem. 261: 8958-8964, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3722184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3722184</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3722184" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="60" class="mim-anchor"></a>
<a id="Steinmann1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Steinmann, B., Rao, V. H., Vogel, A., Bruckner, P., Gitzelmann, R., Byers, P. H.
<strong>Cysteine in the triple-helical domain of one allelic product of the alpha-1(I) gene of type I collagen produces a lethal form of osteogenesis imperfecta.</strong>
J. Biol. Chem. 259: 11129-11138, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6469997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6469997</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6469997" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="61" class="mim-anchor"></a>
<a id="Steinmann1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Steinmann, B., Rao, V. H., Vogel, A., Gitzelmann, R., Byers, P. H.
<strong>A new structural mutation in the alpha-1(I) collagen chain from a patient with type II osteogenesis imperfecta (OI). (Abstract)</strong>
Europ. J. Pediat. 139: 317, 1982.
</p>
</div>
</li>
<li>
<a id="62" class="mim-anchor"></a>
<a id="Steinmann1979" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Steinmann, B. U., Martin, G. R., Baum, B. I., Crystal, R. G.
<strong>Synthesis and degradation of collagen by skin fibroblasts from controls and from patients with osteogenesis imperfecta.</strong>
FEBS Lett. 101: 269-272, 1979.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/446751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">446751</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=446751" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0014-5793(79)81023-6" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="63" class="mim-anchor"></a>
<a id="Steinmann1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Steinmann, B.
<strong>Personal Communication.</strong>
Zurich, Switzerland 12/19/1983.
</p>
</div>
</li>
<li>
<a id="64" class="mim-anchor"></a>
<a id="Stephens1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Stephens, J. D., Filly, R. A., Callen, P. W., Golbus, M. S.
<strong>Prenatal diagnosis of osteogenesis imperfecta type II by real-time ultrasound.</strong>
Hum. Genet. 64: 191-193, 1983.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6885059/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6885059</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6885059" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF00327125" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="65" class="mim-anchor"></a>
<a id="Takagi2011" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Takagi, M., Hori, N., Chinen, Y., Kurosawa, K., Tanaka, Y., Oku, K., Sakata, H., Fukuzawa, R., Nishimura, G., Spranger, J., Hasegawa, T.
<strong>Heterozygous C-propeptide mutations in COL1A1: osteogenesis imperfecta type IIC and dense bone variant.</strong>
Am. J. Med. Genet. 155A: 2269-2273, 2011.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21834035/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21834035</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21834035" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.34152" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="66" class="mim-anchor"></a>
<a id="Thompson1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Thompson, E. M., Young, I. D., Hall, C. M., Pembrey, M. E.
<strong>Recurrence risks and prognosis in severe sporadic osteogenesis imperfecta.</strong>
J. Med. Genet. 24: 390-405, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3612715/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3612715</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3612715" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.24.7.390" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="67" class="mim-anchor"></a>
<a id="Trelstad1977" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Trelstad, R. L., Rubin, D., Gross, J.
<strong>Osteogenesis imperfecta congenita: evidence for a generalized molecular disorder of collagen.</strong>
Lab. Invest. 36: 501-508, 1977.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/865078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">865078</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=865078" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="68" class="mim-anchor"></a>
<a id="Tsipouras1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Tsipouras, P., Bonadio, J. F., Schwartz, R. C., Horwitz, A., Byers, P. H.
<strong>Osteogenesis imperfecta type II is usually due to new dominant mutations. (Abstract)</strong>
Am. J. Hum. Genet. 37: A79, 1985.
</p>
</div>
</li>
<li>
<a id="69" class="mim-anchor"></a>
<a id="Turakainen1980" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Turakainen, H., Larjava, H., Saarni, H., Penttinen, R.
<strong>Synthesis of hyaluronic acid and collagen in skin fibroblasts cultured from patients with osteogenesis imperfecta.</strong>
Biochim. Biophys. Acta 628: 388-397, 1980.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6768402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6768402</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6768402" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0304-4165(80)90388-8" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="70" class="mim-anchor"></a>
<a id="Williams1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Williams, C. J., Prockop, D. J.
<strong>Synthesis and processing of a type I procollagen containing shortened pro-alpha-1(I) chains by fibroblasts from a patient with osteogenesis imperfecta.</strong>
J. Biol. Chem. 258: 5915-5921, 1983.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6304100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6304100</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6304100" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="71" class="mim-anchor"></a>
<a id="Wilson1974" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wilson, M. G.
<strong>Congenital osteogenesis imperfecta.In: Bergsma, D. : Skeletal Dysplasias.</strong>
Amsterdam: Excerpta Medica (pub.) 1974. Pp. 296-298.
</p>
</div>
</li>
<li>
<a id="72" class="mim-anchor"></a>
<a id="Young1980" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Young, I. D., Harper, P. S.
<strong>Recurrence risk in osteogenesis imperfecta congenita. (Letter)</strong>
Lancet 315: 432 only, 1980. Note: Originally Volume I.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6101893/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6101893</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6101893" 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/s0140-6736(80)90988-5" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="73" class="mim-anchor"></a>
<a id="Young1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Young, I. D., Thompson, E. M., Hall, C. M., Pembrey, M. E.
<strong>Osteogenesis imperfecta type IIA: evidence for dominant inheritance.</strong>
J. Med. Genet. 24: 386-389, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3612714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3612714</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3612714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.24.7.386" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="74" class="mim-anchor"></a>
<a id="Zeitoun1963" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Zeitoun, M. M., Ibrahim, A. H., Kassem, A. S.
<strong>Osteogenesis imperfecta congenita in dizygotic twins.</strong>
Arch. Dis. Child. 38: 289-291, 1963.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14003395/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14003395</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14003395" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/adc.38.199.289" 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">
Nara Sobreira - updated : 4/2/2013
</span>
</div>
</div>
<div class="row collapse" id="mimCollapseContributors">
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
George E. Tiller - updated : 7/31/2009<br>Ada Hamosh - updated : 7/25/2007<br>Victor A. McKusick - updated : 11/24/1998
</span>
</div>
</div>
</div>
<div>
<a id="creationDate" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="text-nowrap mim-text-font">
Creation Date:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Victor A. McKusick : 6/2/1986
</span>
</div>
</div>
</div>
<div>
<a id="editHistory" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="text-nowrap mim-text-font">
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
carol : 01/18/2023
</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 : 01/17/2023<br>carol : 05/02/2022<br>carol : 07/09/2016<br>carol : 12/7/2015<br>carol : 4/2/2013<br>terry : 8/31/2012<br>carol : 10/6/2011<br>carol : 10/6/2011<br>terry : 9/21/2010<br>carol : 9/21/2010<br>wwang : 8/13/2009<br>terry : 7/31/2009<br>terry : 2/4/2009<br>alopez : 8/2/2007<br>terry : 7/25/2007<br>alopez : 3/19/2007<br>alopez : 3/16/2007<br>alopez : 3/16/2007<br>alopez : 3/16/2007<br>carol : 7/26/1999<br>carol : 11/24/1998<br>terry : 6/4/1996<br>mark : 5/22/1995<br>mimadm : 12/2/1994<br>terry : 7/29/1994<br>pfoster : 4/25/1994<br>carol : 6/24/1992<br>carol : 5/4/1992
</span>
</div>
</div>
</div>
</div>
</div>
</div>
<div class="container visible-print-block">
<div class="row">
<div class="col-md-8 col-md-offset-1">
<div>
<div>
<h3>
<span class="mim-font">
<strong>#</strong> 166210
</span>
</h3>
</div>
<div>
<h3>
<span class="mim-font">
OSTEOGENESIS IMPERFECTA, TYPE II; OI2
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<div >
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
OI, TYPE II<br />
OSTEOGENESIS IMPERFECTA CONGENITA, PERINATAL LETHAL FORM<br />
OSTEOGENESIS IMPERFECTA CONGENITA; OIC<br />
VROLIK TYPE OF OSTEOGENESIS IMPERFECTA
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<p>
<span class="mim-text-font">
<strong>SNOMEDCT:</strong> 205496008, 254110009, 7134007; &nbsp;
<strong>ORPHA:</strong> 216804, 666; &nbsp;
<strong>DO:</strong> 0110341; &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">
7q21.3
</span>
</td>
<td>
<span class="mim-font">
Osteogenesis imperfecta, type II
</span>
</td>
<td>
<span class="mim-font">
166210
</span>
</td>
<td>
<span class="mim-font">
Autosomal dominant
</span>
</td>
<td>
<span class="mim-font">
3
</span>
</td>
<td>
<span class="mim-font">
COL1A2
</span>
</td>
<td>
<span class="mim-font">
120160
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
17q21.33
</span>
</td>
<td>
<span class="mim-font">
Osteogenesis imperfecta, type II
</span>
</td>
<td>
<span class="mim-font">
166210
</span>
</td>
<td>
<span class="mim-font">
Autosomal dominant
</span>
</td>
<td>
<span class="mim-font">
3
</span>
</td>
<td>
<span class="mim-font">
COL1A1
</span>
</td>
<td>
<span class="mim-font">
120150
</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 osteogenesis imperfecta type II (OI2) is caused by heterozygous mutation in the COL1A1 gene (120150) or the COL1A2 gene (120160).</p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Description</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Osteogenesis imperfecta type II (OI2) is a connective tissue disorder characterized by bone fragility, with many perinatal fractures, severe bowing of long bones, undermineralization, and death in the perinatal period due to respiratory insufficiency (Sillence et al., 1979; Barnes et al., 2006). </p><p>Also see osteogenesis imperfecta type VII (OI7; 610682), an autosomal recessive form of lethal OI caused by mutation in the CRTAP gene (605497).</p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Clinical Features</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Morphologically there appear to be 2 forms of OI congenita, a thin-boned and a broad-boned type. The latter is well illustrated by the male and female sibs reported by Remigio and Grinvalsky (1970). The diagnosis is in question, however, because one had dislocated lenses, aortic coarctation, and basophilic and mucoid changes in the connective tissue of the heart valves and aorta, while the other had less pronounced changes of the same nature in the aorta. Parental consanguinity was denied. Shapiro et al. (1982) suggested that the sibs reported by Remigio and Grinvalsky (1970) may have had another variant because of conspicuous extraskeletal features. The broad-bone type is also illustrated in Figure 8-3 by McKusick (1972) and the thin-bone type in Figure 8-5. The 'broad-bone' form of osteogenesis imperfecta and type IA achondrogenesis (200600) bear similarities. In the latter condition the ribs are thin and prone to fractures but the long bones of the limbs are severely shortened and bowed. </p><p>In a study in Australia, Sillence et al. (1979) encountered a seemingly recessively inherited lethal perinatal OI with radiologically crumpled femora and beaded ribs--the 'broad-bone' type. </p><p>By scanning electron microscopy, Levin et al. (1982) found no abnormality of the teeth in a case of OI congenita with death from pneumonia at age 10 months. Since abnormalities have been described in reported cases, these results may reflect heterogeneity in OI congenita. Levin et al. (1982) suggested that the case best fits OI type III of Sillence et al. (1979). They agreed with Sillence et al. (1979) that the term 'congenita' has limited usefulness since it merely indicates that fractures were present at birth--a feature that may occur in type I (166200), II, or III (259420). </p><p>Elejalde and de Elejalde (1983) observed a family in which the fourth child had OIC and died a few hours after birth, and OIC was diagnosed at 17 weeks' gestation in the fifth pregnancy by ultrasonography. Diagnosis was based on low echogenic properties of all bones, abnormally shaped skull and rib cage, distally thinned ribs, and short, deformed long bones with wide metaphyses and thin diaphyses. </p><p>Radiographically the disorder reported by Buyse and Bull (1978) in 3 sibs (see 259410) was indistinguishable from Sillence's group A (see HISTORY), and chondroosseous histopathology was also identical; however, low birth weight, microcephaly, and cataracts were also present. The patients may, of course, have been homozygous for 2 separate but linked mutations or for a small chromosomal aberration.</p><p>Byers et al. (2006) published practice guidelines for the genetic evaluation of suspected OI. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Inheritance</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Autosomal recessive inheritance of osteogenesis imperfecta had been proposed, but in most well-studied cases the diagnosis was found to be in error or a parent was mosaic for a heterozygous mutation in a collagen I gene. Smars et al. (1961), McKusick (1962), Awwaad and Reda (1960), and others described families with 2 or more sibs thought to have OIC but with ostensibly normal parents. Such is probably to be expected of a dominant trait with wide expressivity and does not require a recessive explanation. Hanhart (1951), however, described an inbred kindred with affected members in 5 sibships. Here germinal mosaicism is not a satisfactory explanation. In all such studies, care must be taken not to confuse hypophosphatasia (e.g., 241500) for osteogenesis imperfecta.</p><p>Kaplan and Baldino (1953) described a kindred derived from an inbred, Arabic-speaking, polygamous sect called the Mozabites, living in southern Algeria. Nine cases occurred in 4 sibships among the descendants. Kaplan et al. (1958) and Laplane et al. (1959), in a follow-up of the same kindred, described 19 cases. Parental consanguinity was noted by several authors, including Freund and Lehmacher (1954) and Rohwedder (1953); the latter described a case in which the parents were brother and sister. </p><p>Meyer (1955) reported 'atypical osteogenesis imperfecta' in several of the 11 offspring of a mentally defective woman by her own father. Manifestations were spontaneous fractures, generalized osteoporosis, and Wormian bones in the area of the lambdoidal sutures. Blue sclerae and deafness were not present. </p><p>Young and Harper (1980) concluded that autosomal recessive inheritance is unlikely to apply to most cases of OIC, including the 'thick boned' variety. They had information on 79 cases with multiple fractures present at birth. In only 3 families was more than 1 affected child born to normal parents and only 1 of the 79 families had consanguineous parents. The empiric recurrence risk figure is probably closer to 3% than 25%. </p><p>Thompson et al. (1987) thought that recessive inheritance was likely for Sillence subclassification group B of type II OI (see HISTORY) because of the frequency of parental consanguinity and multiple affected sibs. On the other hand, the evidence for dominant inheritance was strong in the case of group A (Young et al., 1987). Young et al. (1987) ascertained 30 cases of radiologically proven type II osteogenesis imperfecta of the Sillence group A subclassification. All were isolated cases, with 19 unaffected foreborn and 19 unaffected afterborn sibs. Two sets of parents, both Asian, were consanguineous. Paternal age effect was observed. </p><p>Byers et al. (1988) collected family data and radiographs for 71 probands with the perinatal lethal form of OI and analyzed the collagens synthesized by dermal fibroblasts cultured from 43 of the probands, 19 parental pairs, and single parents of each of 4 additional probands. In 65 families for which there were complete data, there was recurrence of OI II in 5 families such that 6 (8.6%) of 70 sibs were affected. In 2 families with recurrence, the radiographic phenotype was milder than that for the remainder; and 1 of those families was consanguineous, suggesting autosomal recessive inheritance. In the remaining 3 families there was no evidence of consanguinity, but in one of them gonadal mosaicism in the mother was suspected because 3 affected children were born of 2 different fathers. Biochemical studies indicated that the OI II phenotype is basically heterogeneous, that most cases result from new dominant mutations in the genes encoding type I collagen, and that some recurrences can be accounted for by gonadal mosaicism in one of the parents. </p><p>Daw et al. (1990) reported a remarkable family in which lethal OI of the thin-boned type occurred in 6 sibs with normal, unrelated parents. Daw et al. (1990) suggested that this was an instance of gonadal mosaicism for a dominant mutation.</p><p>Bonadio et al. (1990) described an infant apparently homozygous for a point mutation in the COL1A1 gene (120150.0039), a G-to-A transition at the +5 position within the spliced donor site of intron 14. In both parents, who were normal and unrelated, Bonadio et al. (1990) found absence of the mutation in all cells studied. They found evidence for uniparental disomy for chromosome 17 (Bonadio, 1990), however. This mutation, combined with uniparental disomy, may be responsible for the functionally homozygous state of the mutation in this infant. Bonadio (1992) had not had an opportunity to study the possibility further. </p><p>What one might call pseudorecessive inheritance has been observed in lethal OI congenita, which, as noted earlier, is almost always a new autosomal dominant mutation. Cohn et al. (1990) and Edwards et al. (1992) observed 2 offspring with lethal OI and demonstrated mosaicism in 1 parent. In the first case, the mutation was in the COL1A1 gene (120150.0016) and the mother had the mosaicism and was mildly affected. In the second case, the mutation was in the COL1A2 gene (120160.0019) and it was the father who was mosaic. His only manifestations of OI were shorter stature than his unaffected male relatives and mild dentinogenesis imperfecta. </p><p>In an investigation of paternal age in 106 cases of nonfamilial osteogenesis imperfecta compared with matched controls, Orioli et al. (1995) found only slightly elevated mean paternal age in a South American collaboration and no increase in an Italian collaboration. This was in contrast to the findings in 78 achondroplasia (100800) patients, in which a mean paternal age was greatly increased, and in 64 cases of thanatophoric dysplasia (see 187600), in which it was less strikingly elevated. </p><p>Cole and Dalgleish (1995) estimated the recurrence rate at 7%, owing to germline mosaicism in 1 parent. </p><p>From molecular genetic studies of 39 cases from a series totaling 65 (40M; 25F), Tsipouras et al. (1985) concluded that most cases of OI II are the result of new dominant mutation. They observed no parental age effect.</p><p>Horwitz et al. (1985) presented evidence that maternal gonadal mosaicism was responsible for 3 infants with OI II with 2 different fathers.</p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Biochemical Features</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In a deceased 4-day-old infant with OIC, Trelstad et al. (1977) found that the collagen of bone had twice normal content of hydroxylysine and cartilage collagen, a 55% increase. The levels of covalently bound glucose and galactose were proportionately increased. Francis et al. (1981) found increased ratio of alpha-1(I) to alpha-2(I) and of alpha-1(III) to alpha-2(I) in both clinically normal parents of a child with severe OI. </p><p>Barsh and Byers (1981) restudied the cultured cells from a multiply studied patient from the Johns Hopkins Hospital with perinatal lethal osteogenesis imperfecta. This case was the basis of the report by Penttinen et al. (1975) which provided evidence that one form of OIC has a defect in synthesis of type I collagen. The clinical findings in this case were reported by Heller et al. (1975) and the cultured fibroblasts were also studied by Delvin et al. (1979), Steinmann et al. (1979), and Turakainen et al. (1980). Barsh and Byers (1981) found that the cells produced 2 distinct pro-alpha-1 chains of type I collagen, which were synthesized at the same rate. Analysis of cyanogen bromide peptides indicated that the 2 chains differed in their primary structures. Thus, structural abnormalities of type I procollagen prevented this molecule from being secreted normally, resulting in an anomalously low ratio of type I procollagen to other extracellular matrix molecules. In 4 phenotypically identical patients, a defect in secretion of type I procollagen was demonstrated. Thus, although lethal OI congenita is probably heterogeneous, one form may be autosomal dominant new mutational in nature and have a defect in secretion of type I collagen. </p><p>Byers et al. (1984) gave an update based on new biochemical information. </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 studies of material from the patient of Penttinen et al. (1975) and Heller et al. (1975), Williams and Prockop (1983) found deletion of about 500 bp in the gene for pro-alpha-1(I). See also Chu et al. (1983). This was probably the first characterization of a collagen gene defect. The deletion left coding sequences in register on either side. As a result, the mutant allele was expressed and half the pro-alpha-1 chains synthesized by fibroblasts were shortened by about 80 amino acids. Three-fourths of the procollagen trimers synthesized by fibroblasts contained either 1 or 2 shortened pro-alpha chains. The shortening was such that the presence of even 1 of the mutant pro-alpha-1 chains in a procollagen molecule prevented it from folding into a triple-helical configuration. Trimers containing 1 or 2 mutant pro-alpha-1 chains were rapidly degraded. Prockop (1984) called this 'protein suicide.' In further studies Chu et al. (1985) showed that the deletion eliminated 3 exons of the triple helical domain. The termini of the rearrangement were located within 2 short inverted repeats, suggesting that the self-complementary nature of these DNA elements favored formation of an intermediate that was the basis of the deletion. The patient's fibroblasts contained elevated type III collagen (120180) mRNA. The severity of the clinical presentation (with avulsion of the head and an arm during delivery) is explained. A null allele for pro-alpha-2 chains had much less deleterious effect (de Wet et al., 1983). </p><p>Steinmann et al. (1982) and Steinmann et al. (1984) studied material from a male newborn with the lethal perinatal form of OI (and avulsion of an arm). The mother had the Marfan syndrome, as did several other members of the kindred including 2 sibs of the OI proband. The father was healthy and young. The infant's dermis was thinner and collagen fibrils were smaller in diameter than normal and fibroblasts showed dilated endoplasmic reticulum filled with granular material. Cultured fibroblasts synthesized 2 different species of pro-alpha-1(I) chains in about equal amounts. One chain was normal; the other contained cysteine in the triple-helical portion of the COOH-terminal cyanogen bromide peptide alpha-1(I)CB6. Collagen molecules that contained 2 copies of the mutant chain formed alpha-1(I)-dimers linked through interchain disulfide bonds. Molecules containing either 1 or 2 mutant chains were delayed in secretion and underwent excessive posttranslational modification with resulting increased lysyl hydroxylation and hydroxylysyl glycosylation. Delay in triple-helix formation seemed to be responsible for the increased modification. Neither parent had a demonstrable abnormality of collagen. The authors suspected a point mutation with substitution of cysteine for glycine. This may have been the first known example of a point mutation in a collagen gene (Steinmann, 1983). The role of the mother's Marfan syndrome is unclear; the molecular defect underlying the Marfan syndrome in this family had not been determined and it was not known whether the infant inherited the Marfan gene from the mother. The triple-helical domain of type I collagen contains no cysteine. It is made up of repeating triplets of amino acids Gly-X-Y where X and Y are any amino acid except tryptophan, tyrosine, and cysteine and most commonly proline and hydroxyproline, respectively. The fact that type III collagen contains cysteine (and tyrosine) in its triple-helical domain may indicate that its substitution for X or Y in type I collagen would not have as disruptive effects as observed here. In the lethal case thought by Steinmann et al. (1984) to represent a point mutation, Cohn et al. (1986) indeed found substitution of cysteine for glycine at position 988 of the triple-helical portion of half of the alpha-1(I) chains of type I collagen (120150.0018). The mutation disrupted the (G-X-Y)n pattern necessary for formation of the triple helix. This experiment of nature established the minimal mutation capable of producing lethal disease, and the lethality indicated the selective mechanism for stringent maintenance of collagen gene structure. A possibly high mutation rate for the OI II phenotype, which may be at least as frequent as 1 in 60,000 births, can be explained, even if most of them are dominants of the type described here. The COL1A1 gene may present a large target for lethal mutations because any change in the first 2 positions of the repeated GGN-NNN-NNN nucleotide sequence that encodes the triple-helical tripeptide Gly-X-Y is likely to be lethal if it occurs in the part of the gene encoding the carboxy-terminal half of the triple helix. </p><p>Since the substitution of cysteine for glycine at position 988 of COL1A1 (120150.0018) was in the critical first position of the G-X-Y triplet, the mutation in the heterozygous state caused a lethal clinical picture. Sequence data confirmed that the mutation was a single base G-to-T change (Cohn et al., 1986). Conversely, Steinmann et al. (1986) found that the substitution of cysteine in the same domain of the alpha-1 chain in another family resulted in mild autosomal dominant OI (166200). The difference resulted from the fact that the substitution of cysteine was for X or Y rather than for G in the G-X-Y triplet. </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>Bodian et al. (2009) screened DNA samples from 62 unrelated individuals with the perinatal lethal form of OI and identified COL1A1 or COL1A2 mutations in 59 samples and CRTAP or LEPRE1 (610339) mutations in 3 samples. The authors identified 61 distinct heterozygous mutations in the COL1A1 and COL1A2 genes, including 5 nonsynonymous rare variants of unknown significance. Sixty SNPs in the COL1A1 gene (including 17 novel variants) and 82 SNPs in COL1A2 (including 18 novel variants) were reported. Their findings suggested a frequency of 5% for CRTAP and LEPRE1 recessive mutations in severe/lethal OI. A computer model for predicting the outcome of glycine substitutions within the triple-helical domain of COL1A1 chains predicted lethality with 90% accuracy (26 of 29 mutations). </p><p>Takagi et al. (2011) studied 4 Japanese patients, including 2 unrelated patients with what the authors called 'classic OI IIC' (see HISTORY) and 2 sibs with features of 'OI IIC' but less distortion of the tubular bones (OI dense bone variant). No consanguinity was reported in their parents. In both sibs and 1 sporadic patient, they identified heterozygous mutations in the C-propeptide region of COL1A1 (120150.0069 and 120150.0070, respectively), whereas no mutation in this region was identified in the other sporadic patient. Familial gene analysis revealed somatic mosaicism of the mutation in the clinically unaffected father of the sibs, whereas their mother and healthy older sister did not have the mutation. Histologic examination in the 2 sporadic cases showed a network of broad, interconnected cartilaginous trabeculae with thin osseous seams in the metaphyseal spongiosa. Thick, cartilaginous trabeculae (cartilaginous cores) were also found in the diaphyseal spongiosa. Chondrocyte columnization appeared somewhat irregular. These changes differed from the narrow and short metaphyseal trabeculae found in other lethal or severe cases of OI. Takagi et al. (2011) concluded that heterozygous C-propeptide mutations in the COL1A1 gene may result in OI IIC with or without twisting of the long bones and that OI IIC appears to be inherited as an autosomal dominant trait. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Nomenclature</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>The autosomal recessive form of lethal OI designated OI VII (610682) had previously been designated OI IIB (OI2B). For a short time, the autosomal dominant form of lethal OI (OI II; OI2) was designated OI IIA (OI2A).</p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>History</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Sillence et al. (1984) reviewed 48 cases of the perinatal lethal form of OI (OI type II) and subclassified them into 3 categories on the basis of radiologic features: group A (38 cases)--short, broad, 'crumpled' long bones, angulation of tibias and continuously beaded ribs; group B (6 cases)--short, broad, crumpled femurs, angulation of tibias but normal ribs or ribs with incomplete beading; and group C (4 cases)--long, thin, inadequately modeled long bones with multiple fractures and thin beaded ribs. Information for segregation analysis was available on 33 families. Two or more sibs were affected in 6 of the families; 3 of these 6 families were examined by the authors and found to fall into group A, 2 into group B, and 1 into group C. The parents were related in 1 family of type A and 1 family of type C. Mean paternal age was not increased. For all these reasons, Sillence et al. (1984) concluded that most cases of OI II represent an autosomal recessive disorder. There is, however, clearly an autosomal dominant form as indicated by biochemical evidence provided by the studies of Barsh and Byers (1981) that there are 2 types of collagen I alpha-1 chains synthesized by fibroblasts. </p><p>Commenting on the paper of Sillence et al. (1984), Spranger (1984) stated that 'Type IIC poses no major nosologic problems' because of the radiologic distinctiveness. </p><p>On radiographic grounds, Tsipouras et al. (1985) suggested that 5 types of type II OI could be distinguished. Five patients in 3 families appeared to have type 5, the least severe form. The parents of these 5 patients were consanguineous, and Tsipouras et al. (1985) suggested that the inheritance of type 5 may be autosomal recessive.</p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Heterogeneity</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Aitchison et al. (1988) studied a child with type II OI of Sillence subclassification B who was the product of consanguineous Pakistani parents. A brother and sister of the proband's mother, also the product of a consanguineous mating, had died with OI in the perinatal period. The proband was heterozygous for COL1A1 and COL1A2 genotypes, suggesting that the mutation causing the disease in this child was not at either of the structural genes for type I collagen. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Animal Model</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Stacey et al. (1988) reproduced the OI II phenotype in transgenic mice carrying a mutant alpha-1(I) collagen gene into which specific glycine substitutions had been engineered. The experiments reproduced the findings in patients in whom a single point mutation resulted in OIC: substitution of glycine by arginine at position 391 (Bateman et al., 1987) or substitution of glycine by cysteine at position 988 (Cohn et al., 1986). Constantinou et al. (1989) described a lethal variant of OI in which a G-to-T substitution converted glycine to cysteine at position 904 of the COL1A1 gene. In addition, the proband may have inherited a second mutation from her asymptomatic mother that produced an overmodified and thermally unstable species of type I procollagen. Her mother was somewhat short and had slightly blue sclerae. Lamande et al. (1989) used the method of Cotton et al. (1988) to identify single base changes in the subunits of type I collagen in 5 patients with OIC. In 4 cases, the substitution was found in the alpha-1 subunit, and in 1 it was located in the alpha-2 chain. In all 5 cases, the first glycine in the amino acid triplet was replaced: gly-973 and gly-1006 to val, gly-928 to ala, and gly-976 to arg in the alpha-1 chain and gly-865 to ser in the alpha-2 chain. These mutations emphasize the importance of the Gly-X-Y repeating amino acid triplet for normal collagen helix formation and function. The method of Cotton et al. (1988) exploits the increased chemical modification of cytosines by hydroxylamine and of thymines by osmium tetroxide, when they are not paired with their complementary base. The DNA chain is then cleaved at the modified bases with piperidine. The use of radioactively end-labeled DNA probes allows the position of the mismatched cytosines and thymines in the probe to be determined by electrophoresis of the cleavage products. Cole et al. (1992) described the occurrence of premature birth in OIC due to precocious rupture of membranes and antepartum hemorrhage. </p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>See Also:</strong>
</span>
</h4>
<span class="mim-text-font">
Bateman et al. (1984); Braga and Passarge (1981); Goldfarb and Ford
(1954); Goldman et al. (1980); Horan and Beighton (1975); Ibsen
(1967); Pihlajaniemi et al. (1984); Schroder (1964); Stephens et al.
(1983); Wilson (1974); Zeitoun et al. (1963)
</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">
Aitchison, K., Ogilvie, D., Honeyman, M., Thompson, E., Sykes, B.
<strong>Homozygous osteogenesis imperfecta unlinked to collagen I genes.</strong>
Hum. Genet. 78: 233-236, 1988.
[PubMed: 2894346]
[Full Text: https://doi.org/10.1007/BF00291667]
</p>
</li>
<li>
<p class="mim-text-font">
Awwaad, S., Reda, M.
<strong>Osteogenesis imperfecta: review of literature and a report on three cases.</strong>
Arch. Pediat. 77: 280-290, 1960.
</p>
</li>
<li>
<p class="mim-text-font">
Barnes, A. M., Chang, W., Morello, R., Cabral, W. A., Weis, M., Eyre, D. R., Leikin, S., Makareeva, E., Kuznetsova, N., Uveges, T. E., Ashok, A., Flor, A. W., Mulvihill, J. J., Wilson, P. L., Sundaram, U. T., Lee, B., Marini, J. C.
<strong>Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta.</strong>
New Eng. J. Med. 355: 2757-2764, 2006.
[PubMed: 17192541]
[Full Text: https://doi.org/10.1056/NEJMoa063804]
</p>
</li>
<li>
<p class="mim-text-font">
Barsh, G. S., Byers, P. H.
<strong>Reduced secretion of structurally abnormal type I procollagen in a form of osteogenesis imperfecta.</strong>
Proc. Nat. Acad. Sci. 78: 5142-5146, 1981.
[PubMed: 6946461]
[Full Text: https://doi.org/10.1073/pnas.78.8.5142]
</p>
</li>
<li>
<p class="mim-text-font">
Bateman, J. F., Chan, D., Walker, I. D., Rogers, J. G., Cole, W. G.
<strong>Lethal perinatal osteogenesis imperfecta due to the substitution of arginine for glycine at residue 391 of the alpha-1(I) chain of type I collagen.</strong>
J. Biol. Chem. 262: 7021-7027, 1987.
[PubMed: 3108247]
</p>
</li>
<li>
<p class="mim-text-font">
Bateman, J. F., Mascara, T., Chan, D., Cole, W. G.
<strong>Abnormal type I collagen metabolism by cultured fibroblasts in lethal perinatal osteogenesis imperfecta.</strong>
Biochem. J. 217: 103-115, 1984.
[PubMed: 6421277]
[Full Text: https://doi.org/10.1042/bj2170103]
</p>
</li>
<li>
<p class="mim-text-font">
Bodian, D. L., Chan, T.-F., Poon, A., Schwarze, U., Yang, K., Byers, P. H., Kwok, P.-Y., Klein, T. E.
<strong>Mutation and polymorphism spectrum in osteogenesis imperfecta type II: implications for genotype-phenotype relationships.</strong>
Hum. Molec. Genet. 18: 463-471, 2009. Note: Erratum: Hum. Molec. Genet. 18: 1893-1895, 2009.
[PubMed: 18996919]
[Full Text: https://doi.org/10.1093/hmg/ddn374]
</p>
</li>
<li>
<p class="mim-text-font">
Bonadio, J., Ramirez, F., Barr, M.
<strong>An intron mutation in the human alpha-1(I) collagen gene alters the efficiency of pre-mRNA splicing and is associated with osteogenesis imperfecta type II.</strong>
J. Biol. Chem. 265: 2262-2268, 1990.
[PubMed: 2298750]
</p>
</li>
<li>
<p class="mim-text-font">
Bonadio, J.
<strong>Personal Communication.</strong>
Ann Arbor, Mich. 3/1990.
</p>
</li>
<li>
<p class="mim-text-font">
Bonadio, J.
<strong>Personal Communication.</strong>
Ann Arbor, Mich. 2/7/1992.
</p>
</li>
<li>
<p class="mim-text-font">
Braga, S., Passarge, E.
<strong>Congenital osteogenesis imperfecta in three sibs.</strong>
Hum. Genet. 58: 441-443, 1981.
[PubMed: 7327569]
[Full Text: https://doi.org/10.1007/BF00282834]
</p>
</li>
<li>
<p class="mim-text-font">
Buyse, M., Bull, M. J.
<strong>A syndrome of osteogenesis imperfecta, microcephaly, and cataracts.</strong>
Birth Defects Orig. Art. Ser. XIV(6B): 95-98, 1978.
</p>
</li>
<li>
<p class="mim-text-font">
Byers, P. H., Bonadio, J. F., Steinmann, B.
<strong>Osteogenesis imperfecta: update and perspective. (Editorial)</strong>
Am. J. Med. Genet. 17: 429-435, 1984.
[PubMed: 6702896]
[Full Text: https://doi.org/10.1002/ajmg.1320170206]
</p>
</li>
<li>
<p class="mim-text-font">
Byers, P. H., Krakow, D., Nunes, M. E., Pepin, M.
<strong>Genetic evaluation of suspected osteogenesis imperfecta (OI).</strong>
Genet. Med. 8: 383-388, 2006.
[PubMed: 16778601]
[Full Text: https://doi.org/10.1097/01.gim.0000223557.54670.aa]
</p>
</li>
<li>
<p class="mim-text-font">
Byers, P. H., Tsipouras, P., Bonadio, J. F., Starman, B. J., Schwartz, R. C.
<strong>Perinatal lethal osteogenesis imperfecta (OI type II): a biochemically heterogeneous disorder usually due to new mutations in the genes for type I collagen.</strong>
Am. J. Hum. Genet. 42: 237-248, 1988.
[PubMed: 3341380]
</p>
</li>
<li>
<p class="mim-text-font">
Chu, M.-L., Gargiulo, V., Williams, C. J., Ramirez, F.
<strong>Multiexon deletion in an osteogenesis imperfecta variant with increased type III collagen mRNA.</strong>
J. Biol. Chem. 260: 691-694, 1985.
[PubMed: 2981843]
</p>
</li>
<li>
<p class="mim-text-font">
Chu, M.-L., Williams, C. J., Pepe, G., Hirsch, J. L., Prockop, D. J., Ramirez, F.
<strong>Internal deletion in a collagen gene in a perinatal lethal form of osteogenesis imperfecta.</strong>
Nature 304: 78-80, 1983.
[PubMed: 6191221]
[Full Text: https://doi.org/10.1038/304078a0]
</p>
</li>
<li>
<p class="mim-text-font">
Cohn, D. H., Byers, P. H., Steinmann, B., Gelinas, R. E.
<strong>Lethal osteogenesis imperfecta resulting from a single nucleotide change in one human pro-alpha-1(I) collagen allele.</strong>
Proc. Nat. Acad. Sci. 83: 6045-6047, 1986.
[PubMed: 3016737]
[Full Text: https://doi.org/10.1073/pnas.83.16.6045]
</p>
</li>
<li>
<p class="mim-text-font">
Cohn, D. H., Starman, B. J., Blumberg, B., Byers, P. H.
<strong>Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a dominant mutation in a human type I collagen gene (COL1A1).</strong>
Am. J. Hum. Genet. 46: 591-601, 1990.
[PubMed: 2309707]
</p>
</li>
<li>
<p class="mim-text-font">
Cole, W. G., Dalgleish, R.
<strong>Perinatal lethal osteogenesis imperfecta.</strong>
J. Med. Genet. 32: 284-289, 1995.
[PubMed: 7643358]
[Full Text: https://doi.org/10.1136/jmg.32.4.284]
</p>
</li>
<li>
<p class="mim-text-font">
Cole, W. G., Patterson, E., Bonadio, J., Campbell, P. E., Fortune, D. W.
<strong>The clinicopathological features of three babies with osteogenesis imperfecta resulting from the substitution of glycine by valine in the pro-alpha-1(I) chain of type I procollagen.</strong>
J. Med. Genet. 29: 112-118, 1992.
[PubMed: 1613761]
[Full Text: https://doi.org/10.1136/jmg.29.2.112]
</p>
</li>
<li>
<p class="mim-text-font">
Constantinou, C. D., Nielsen, K. B., Prockop, D. J.
<strong>A lethal variant of osteogenesis imperfecta has a single base mutation that substitutes cysteine for glycine 904 of the alpha-1(I) chain of type I procollagen: the asymptomatic mother has an unidentified mutation producing an overmodified and unstable type I procollagen.</strong>
J. Clin. Invest. 83: 574-584, 1989.
[PubMed: 2913053]
[Full Text: https://doi.org/10.1172/JCI113920]
</p>
</li>
<li>
<p class="mim-text-font">
Cotton, R. G. H., Rodrigues, N. R., Campbell, R. D.
<strong>Reactivity of cytosine and thymine in single-base-pair mismatches with hydroxylamine and osmium tetroxide and its application to the study of mutations.</strong>
Proc. Nat. Acad. Sci. 85: 4397-4401, 1988.
[PubMed: 3260032]
[Full Text: https://doi.org/10.1073/pnas.85.12.4397]
</p>
</li>
<li>
<p class="mim-text-font">
Daw, S. C. M., Gibbs, D. A., Nicholls, A. C., Hall, E. C., Siggers, D. C., Pope, F. M.
<strong>Lethal osteogenesis imperfecta: a family with 6 affected sibs heterozygous for a type I collagen mutation. (Abstract)</strong>
J. Med. Genet. 27: 206, 1990.
</p>
</li>
<li>
<p class="mim-text-font">
de Wet, W. J., Pihlajaniemi, T., Myers, J. C., Kelly, T. E., Prockop, D. J.
<strong>Synthesis of a shortened pro-alpha-2(I) chain and decreased synthesis of pro-alpha-2(I) chains in a patient with osteogenesis imperfecta.</strong>
J. Biol. Chem. 258: 7721-7727, 1983.
[PubMed: 6863261]
</p>
</li>
<li>
<p class="mim-text-font">
Delvin, E. E., Glorieux, F. H., Lopez, E.
<strong>In vitro sulfate turnover in osteogenesis imperfecta congenita and tarda.</strong>
Am. J. Med. Genet. 4: 349-355, 1979.
[PubMed: 539603]
[Full Text: https://doi.org/10.1002/ajmg.1320040406]
</p>
</li>
<li>
<p class="mim-text-font">
Edwards, M. J., Wenstrup, R. J., Byers, P. H., Cohn, D. H.
<strong>Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a mutation in the COL1A2 gene of type I collagen: the mosaic parent exhibits phenotypic features of a mild form of the disease.</strong>
Hum. Mutat. 1: 47-54, 1992.
[PubMed: 1301191]
[Full Text: https://doi.org/10.1002/humu.1380010108]
</p>
</li>
<li>
<p class="mim-text-font">
Elejalde, B. R., de Elejalde, M. M.
<strong>Prenatal diagnosis of perinatally lethal osteogenesis imperfecta.</strong>
Am. J. Med. Genet. 14: 353-359, 1983.
[PubMed: 6837630]
[Full Text: https://doi.org/10.1002/ajmg.1320140215]
</p>
</li>
<li>
<p class="mim-text-font">
Francis, M. J. O., Williams, K. J., Sykes, B. C., Smith, R.
<strong>The relative amounts of the collagen chains alpha-1(I), alpha-2 and alpha-1(III) in the skin of 31 patients with osteogenesis imperfecta.</strong>
Clin. Sci. (Lond.) 60: 617-623, 1981.
[PubMed: 6788428]
[Full Text: https://doi.org/10.1042/cs0600617]
</p>
</li>
<li>
<p class="mim-text-font">
Freund, R., Lehmacher, K.
<strong>Beitrag zur Vererbung der Osteogenesis imperfecta.</strong>
Geburtsh. Frauenheilk. 14: 171-177, 1954.
[PubMed: 13151389]
</p>
</li>
<li>
<p class="mim-text-font">
Goldfarb, A. A., Ford, D., Jr.
<strong>Osteogenesis imperfecta congenita in consecutive siblings.</strong>
J. Pediat. 44: 264-268, 1954.
[PubMed: 13143452]
[Full Text: https://doi.org/10.1016/s0022-3476(54)80315-5]
</p>
</li>
<li>
<p class="mim-text-font">
Goldman, A. B., Davidson, D., Pavlov, H., Bullough, P. G.
<strong>&#x27;Popcorn&#x27; calcifications: a prognostic sign in osteogenesis imperfecta.</strong>
Radiology 136: 351-358, 1980.
[PubMed: 7403509]
[Full Text: https://doi.org/10.1148/radiology.136.2.7403509]
</p>
</li>
<li>
<p class="mim-text-font">
Hanhart, E.
<strong>Ueber eine neue Form von Osteopsathyrosis congenita mit einfach-rezessivem, sowie 4 neue Sippen mit dominantem Erbgang und die Frage der Vererbung der sog. Osteogenesis imperfecta.</strong>
Arch. Klaus Stift. Vererbungsforsch. 26: 426-437, 1951.
</p>
</li>
<li>
<p class="mim-text-font">
Heller, R. H., Winn, K. J., Heller, R. M.
<strong>The prenatal diagnosis of osteogenesis imperfecta congenita.</strong>
Am. J. Obstet. Gynec. 121: 572-573, 1975.
[PubMed: 1146889]
[Full Text: https://doi.org/10.1016/0002-9378(75)90101-5]
</p>
</li>
<li>
<p class="mim-text-font">
Horan, F., Beighton, P.
<strong>Autosomal recessive inheritance of osteogenesis imperfecta.</strong>
Clin. Genet. 8: 107-111, 1975.
[PubMed: 1175315]
[Full Text: https://doi.org/10.1111/j.1399-0004.1975.tb04398.x]
</p>
</li>
<li>
<p class="mim-text-font">
Horwitz, A. L., Lazda, V., Byers, P. H.
<strong>Recurrent type II (lethal) osteogenesis imperfecta: apparent dominant inheritance. (Abstract)</strong>
Am. J. Hum. Genet. 37: A59, 1985.
</p>
</li>
<li>
<p class="mim-text-font">
Ibsen, K. H.
<strong>Distinct varieties of osteogenesis imperfecta.</strong>
Clin. Orthop. 50: 279-290, 1967.
[PubMed: 5339474]
</p>
</li>
<li>
<p class="mim-text-font">
Kaplan, M., Baldino, C.
<strong>Dysplasie periostale paraissant familiale et transmise suivant le mode Mendelien recessif.</strong>
Arch. Franc. Pediat. 10: 943-950, 1953.
[PubMed: 13125648]
</p>
</li>
<li>
<p class="mim-text-font">
Kaplan, M., Laplane, M. R., Debray, P., Lasfargues, G.
<strong>Sur l&#x27;heredite de la dysplasie periostale complement a la communication de M. Kaplan et C. Baldino.</strong>
Arch. Franc. Pediat. 15: 1097-1101, 1958.
[PubMed: 13595987]
</p>
</li>
<li>
<p class="mim-text-font">
Lamande, S. R., Dahl, H.-H. M., Cole, W. G., Bateman, J. F.
<strong>Characterization of point mutations in the collagen COL1A1 and COL1A2 genes causing lethal perinatal osteogenesis imperfecta.</strong>
J. Biol. Chem. 264: 15809-15812, 1989.
[PubMed: 2777764]
</p>
</li>
<li>
<p class="mim-text-font">
Laplane, M. R., Lasfargues, G., Debray, P.
<strong>Essai de classification genetique des osteogeneses imparfaites.</strong>
Presse Med. 67: 893-895, 1959.
</p>
</li>
<li>
<p class="mim-text-font">
Levin, L. S., Rosenbaum, K. N., Brady, J. M., Dorst, J. P.
<strong>Osteogenesis imperfecta lethal in infancy: case report and scanning electron microscopic studies of the deciduous teeth.</strong>
Am. J. Med. Genet. 13: 359-368, 1982.
[PubMed: 7158636]
[Full Text: https://doi.org/10.1002/ajmg.1320130403]
</p>
</li>
<li>
<p class="mim-text-font">
McKusick, V. A.
<strong>Medical genetics 1961.</strong>
J. Chronic Dis. 15: 417-572, 1962. Fig. 50.
</p>
</li>
<li>
<p class="mim-text-font">
McKusick, V. A.
<strong>Heritable Disorders of Connective Tissue. (4th ed.)</strong>
St. Louis: C. V. Mosby (pub.) 1972.
</p>
</li>
<li>
<p class="mim-text-font">
Meyer, H. J.
<strong>Atypical osteogenesis imperfecta: Lobstein&#x27;s disease.</strong>
Arch. Pediat. 72: 182-186, 1955.
[PubMed: 13249697]
</p>
</li>
<li>
<p class="mim-text-font">
Orioli, I. M., Castilla, E. E., Scarano, G., Mastroiacovo, P.
<strong>Effect of paternal age in achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta.</strong>
Am. J. Med. Genet. 59: 209-217, 1995.
[PubMed: 8588588]
[Full Text: https://doi.org/10.1002/ajmg.1320590218]
</p>
</li>
<li>
<p class="mim-text-font">
Penttinen, R. P., Lichtenstein, J. R., Martin, G. R., McKusick, V. A.
<strong>Abnormal collagen metabolism in cultured cells in osteogenesis imperfecta.</strong>
Proc. Nat. Acad. Sci. 72: 586-589, 1975.
[PubMed: 1054840]
[Full Text: https://doi.org/10.1073/pnas.72.2.586]
</p>
</li>
<li>
<p class="mim-text-font">
Pihlajaniemi, T., Dickson, L. A., Pope, F. M., Korhonen, V. M., Nicholls, A., Prockop, D. J., Myers, J. C.
<strong>Osteogenesis imperfecta: cloning of a pro-alpha-2(I) collagen gene with a frameshift mutation.</strong>
J. Biol. Chem. 259: 12941-12944, 1984.
[PubMed: 6092353]
</p>
</li>
<li>
<p class="mim-text-font">
Prockop, D. J.
<strong>Osteogenesis imperfecta: phenotypic heterogeneity, protein suicide, short and long collagen.</strong>
Am. J. Hum. Genet. 36: 499-505, 1984.
[PubMed: 6375355]
</p>
</li>
<li>
<p class="mim-text-font">
Remigio, P. A., Grinvalsky, H. T.
<strong>Osteogenesis imperfecta congenita: association with conspicuous extraskeletal connective tissue dysplasia.</strong>
Am. J. Dis. Child. 119: 524-528, 1970.
[PubMed: 5443340]
</p>
</li>
<li>
<p class="mim-text-font">
Rohwedder, H. J.
<strong>Ein Beitrag zur Frage des Erbganges der Osteogenesis imperfecta Vrolik.</strong>
Arch. Kinderheilk. 147: 256-262, 1953.
[PubMed: 13139510]
</p>
</li>
<li>
<p class="mim-text-font">
Schroder, G.
<strong>Eine klinisch-erbbiologische Untersuchung des Krankengutes in Westfalen. Schaetzung der Mutationsraten fuer den Regierungsbezirk Munster (Westfalen).</strong>
Z. Menschl. Vererb. Konstitutionsl. 37: 632-676, 1964.
</p>
</li>
<li>
<p class="mim-text-font">
Shapiro, J. E., Phillips, J. A., Byers, P. H., Sanders, R., Holbrook, K. A., Levin, L. S., Dorst, J., Barsh, G. S., Peterson, K. E., Goldstein, P.
<strong>Prenatal diagnosis of lethal perinatal osteogenesis imperfecta (OI type II).</strong>
J. Pediat. 100: 127-133, 1982.
[PubMed: 7057300]
[Full Text: https://doi.org/10.1016/s0022-3476(82)80252-7]
</p>
</li>
<li>
<p class="mim-text-font">
Sillence, D. O., Barlow, K. K., Garber, A. P., Hall, J. G., Rimoin, D. L.
<strong>Osteogenesis imperfecta type II: delineation of the phenotype with reference to genetic heterogeneity.</strong>
Am. J. Med. Genet. 17: 407-423, 1984.
[PubMed: 6702894]
[Full Text: https://doi.org/10.1002/ajmg.1320170204]
</p>
</li>
<li>
<p class="mim-text-font">
Sillence, D. O., Senn, A., Danks, D. M.
<strong>Genetic heterogeneity in osteogenesis imperfecta.</strong>
J. Med. Genet. 16: 101-116, 1979.
[PubMed: 458828]
[Full Text: https://doi.org/10.1136/jmg.16.2.101]
</p>
</li>
<li>
<p class="mim-text-font">
Smars, G., Beckman, L., Book, J. A.
<strong>Osteogenesis imperfecta and blood groups.</strong>
Acta Genet. Statist. Med. 11: 133-136, 1961.
</p>
</li>
<li>
<p class="mim-text-font">
Spranger, J.
<strong>Osteogenesis imperfecta: a pasture for splitters and lumpers. (Editorial)</strong>
Am. J. Med. Genet. 17: 425-428, 1984.
[PubMed: 6702895]
[Full Text: https://doi.org/10.1002/ajmg.1320170205]
</p>
</li>
<li>
<p class="mim-text-font">
Stacey, A., Bateman, J., Choi, T., Mascara, T., Cole, W., Jaenisch, R.
<strong>Perinatal lethal osteogenesis imperfecta in transgenic mice bearing an engineered mutant pro-alpha-1(I) collagen gene.</strong>
Nature 332: 131-136, 1988.
[PubMed: 2450280]
[Full Text: https://doi.org/10.1038/332131a0]
</p>
</li>
<li>
<p class="mim-text-font">
Steinmann, B., Nicholls, A., Pope, F. M.
<strong>Clinical variability of osteogenesis imperfecta reflecting molecular heterogeneity: cysteine substitutions in the alpha-1(I) collagen chain producing lethal and mild forms.</strong>
J. Biol. Chem. 261: 8958-8964, 1986.
[PubMed: 3722184]
</p>
</li>
<li>
<p class="mim-text-font">
Steinmann, B., Rao, V. H., Vogel, A., Bruckner, P., Gitzelmann, R., Byers, P. H.
<strong>Cysteine in the triple-helical domain of one allelic product of the alpha-1(I) gene of type I collagen produces a lethal form of osteogenesis imperfecta.</strong>
J. Biol. Chem. 259: 11129-11138, 1984.
[PubMed: 6469997]
</p>
</li>
<li>
<p class="mim-text-font">
Steinmann, B., Rao, V. H., Vogel, A., Gitzelmann, R., Byers, P. H.
<strong>A new structural mutation in the alpha-1(I) collagen chain from a patient with type II osteogenesis imperfecta (OI). (Abstract)</strong>
Europ. J. Pediat. 139: 317, 1982.
</p>
</li>
<li>
<p class="mim-text-font">
Steinmann, B. U., Martin, G. R., Baum, B. I., Crystal, R. G.
<strong>Synthesis and degradation of collagen by skin fibroblasts from controls and from patients with osteogenesis imperfecta.</strong>
FEBS Lett. 101: 269-272, 1979.
[PubMed: 446751]
[Full Text: https://doi.org/10.1016/0014-5793(79)81023-6]
</p>
</li>
<li>
<p class="mim-text-font">
Steinmann, B.
<strong>Personal Communication.</strong>
Zurich, Switzerland 12/19/1983.
</p>
</li>
<li>
<p class="mim-text-font">
Stephens, J. D., Filly, R. A., Callen, P. W., Golbus, M. S.
<strong>Prenatal diagnosis of osteogenesis imperfecta type II by real-time ultrasound.</strong>
Hum. Genet. 64: 191-193, 1983.
[PubMed: 6885059]
[Full Text: https://doi.org/10.1007/BF00327125]
</p>
</li>
<li>
<p class="mim-text-font">
Takagi, M., Hori, N., Chinen, Y., Kurosawa, K., Tanaka, Y., Oku, K., Sakata, H., Fukuzawa, R., Nishimura, G., Spranger, J., Hasegawa, T.
<strong>Heterozygous C-propeptide mutations in COL1A1: osteogenesis imperfecta type IIC and dense bone variant.</strong>
Am. J. Med. Genet. 155A: 2269-2273, 2011.
[PubMed: 21834035]
[Full Text: https://doi.org/10.1002/ajmg.a.34152]
</p>
</li>
<li>
<p class="mim-text-font">
Thompson, E. M., Young, I. D., Hall, C. M., Pembrey, M. E.
<strong>Recurrence risks and prognosis in severe sporadic osteogenesis imperfecta.</strong>
J. Med. Genet. 24: 390-405, 1987.
[PubMed: 3612715]
[Full Text: https://doi.org/10.1136/jmg.24.7.390]
</p>
</li>
<li>
<p class="mim-text-font">
Trelstad, R. L., Rubin, D., Gross, J.
<strong>Osteogenesis imperfecta congenita: evidence for a generalized molecular disorder of collagen.</strong>
Lab. Invest. 36: 501-508, 1977.
[PubMed: 865078]
</p>
</li>
<li>
<p class="mim-text-font">
Tsipouras, P., Bonadio, J. F., Schwartz, R. C., Horwitz, A., Byers, P. H.
<strong>Osteogenesis imperfecta type II is usually due to new dominant mutations. (Abstract)</strong>
Am. J. Hum. Genet. 37: A79, 1985.
</p>
</li>
<li>
<p class="mim-text-font">
Turakainen, H., Larjava, H., Saarni, H., Penttinen, R.
<strong>Synthesis of hyaluronic acid and collagen in skin fibroblasts cultured from patients with osteogenesis imperfecta.</strong>
Biochim. Biophys. Acta 628: 388-397, 1980.
[PubMed: 6768402]
[Full Text: https://doi.org/10.1016/0304-4165(80)90388-8]
</p>
</li>
<li>
<p class="mim-text-font">
Williams, C. J., Prockop, D. J.
<strong>Synthesis and processing of a type I procollagen containing shortened pro-alpha-1(I) chains by fibroblasts from a patient with osteogenesis imperfecta.</strong>
J. Biol. Chem. 258: 5915-5921, 1983.
[PubMed: 6304100]
</p>
</li>
<li>
<p class="mim-text-font">
Wilson, M. G.
<strong>Congenital osteogenesis imperfecta.In: Bergsma, D. : Skeletal Dysplasias.</strong>
Amsterdam: Excerpta Medica (pub.) 1974. Pp. 296-298.
</p>
</li>
<li>
<p class="mim-text-font">
Young, I. D., Harper, P. S.
<strong>Recurrence risk in osteogenesis imperfecta congenita. (Letter)</strong>
Lancet 315: 432 only, 1980. Note: Originally Volume I.
[PubMed: 6101893]
[Full Text: https://doi.org/10.1016/s0140-6736(80)90988-5]
</p>
</li>
<li>
<p class="mim-text-font">
Young, I. D., Thompson, E. M., Hall, C. M., Pembrey, M. E.
<strong>Osteogenesis imperfecta type IIA: evidence for dominant inheritance.</strong>
J. Med. Genet. 24: 386-389, 1987.
[PubMed: 3612714]
[Full Text: https://doi.org/10.1136/jmg.24.7.386]
</p>
</li>
<li>
<p class="mim-text-font">
Zeitoun, M. M., Ibrahim, A. H., Kassem, A. S.
<strong>Osteogenesis imperfecta congenita in dizygotic twins.</strong>
Arch. Dis. Child. 38: 289-291, 1963.
[PubMed: 14003395]
[Full Text: https://doi.org/10.1136/adc.38.199.289]
</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">
Nara Sobreira - updated : 4/2/2013<br>George E. Tiller - updated : 7/31/2009<br>Ada Hamosh - updated : 7/25/2007<br>Victor A. McKusick - updated : 11/24/1998
</span>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Creation Date:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Victor A. McKusick : 6/2/1986
</span>
</div>
</div>
</div>
<div>
<br />
</div>
<div>
<div class="row">
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
<span class="text-nowrap mim-text-font">
Edit History:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
carol : 01/18/2023<br>carol : 01/17/2023<br>carol : 05/02/2022<br>carol : 07/09/2016<br>carol : 12/7/2015<br>carol : 4/2/2013<br>terry : 8/31/2012<br>carol : 10/6/2011<br>carol : 10/6/2011<br>terry : 9/21/2010<br>carol : 9/21/2010<br>wwang : 8/13/2009<br>terry : 7/31/2009<br>terry : 2/4/2009<br>alopez : 8/2/2007<br>terry : 7/25/2007<br>alopez : 3/19/2007<br>alopez : 3/16/2007<br>alopez : 3/16/2007<br>alopez : 3/16/2007<br>carol : 7/26/1999<br>carol : 11/24/1998<br>terry : 6/4/1996<br>mark : 5/22/1995<br>mimadm : 12/2/1994<br>terry : 7/29/1994<br>pfoster : 4/25/1994<br>carol : 6/24/1992<br>carol : 5/4/1992
</span>
</div>
</div>
</div>
<div>
<br />
</div>
</div>
</div>
</div>
</div>
<div id="mimFooter">
<div class="container ">
<div class="row">
<br />
<br />
</div>
</div>
<div class="hidden-print mim-footer">
<div class="container">
<div class="row">
<p />
</div>
<div class="row text-center small">
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
<br />
OMIM<sup>&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 5, 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