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Entry
- #309900 - MUCOPOLYSACCHARIDOSIS, TYPE II; MPS2
- OMIM
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<span class="h4">#309900</span>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/309900"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS607014"> <strong>Phenotypic Series</strong> </a>
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<a href="#inheritance">Inheritance</a>
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<a href="#mapping">Mapping</a>
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<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>
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=18824&Typ=Pat" title="Mucopolysaccharidosis type 2, severe form" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Mucopolysaccharidosis type…&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=18825&Typ=Pat" title="Mucopolysaccharidosis type 2, attenuated form" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Mucopolysaccharidosis type…&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=131&Typ=Pat" title="Mucopolysaccharidosis type 2" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Mucopolysaccharidosis type…&nbsp;</a></div>
</div>
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1274/" 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="#mimMedlinePlusGeneticsFold" id="mimMedlinePlusGeneticsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Consumer-friendly information about the effects of genetic variation on human health."><span id="mimMedlinePlusGeneticsToggleTriangle" class="small" style="margin-left: -0.8em;">&#9658;</span>MedlinePlus Genetics</div>
<div id="mimMedlinePlusGeneticsFold" class="collapse">
<div style="margin-left: 0.5em;"><a href="https://medlineplus.gov/genetics/condition/mucopolysaccharidosis-type-ii" title="Mucopolysaccharidosis type II" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">Mucopolysaccharidosis type…&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://medlineplus.gov/genetics/gene/ids" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">IDS gene&nbsp;</a></div>
</div>
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=309900[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=217085" title="Mucopolysaccharidosis type 2, severe form" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Mucopolysaccharidosis type…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=217093" title="Mucopolysaccharidosis type 2, attenuated form" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Mucopolysaccharidosis type…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=580" title="Mucopolysaccharidosis type 2" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Mucopolysaccharidosis type…</a></div>
</div>
<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/0f3e59bf-e1b8-4a71-87b9-144e6cc5de40/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="mimVariation">
<span class="panel-title">
<span class="small">
<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">&#9658;</span> Variation
</a>
</span>
</span>
</div>
<div id="mimVariationLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="http://www.LOVD.nl/IDS" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
</div>
</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:12799" 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/309900" 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/OMIA001317/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
</div>
</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:309900" 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> 70737009<br />
<strong>ICD10CM:</strong> E76.1<br />
<strong>ORPHA:</strong> 217085, 217093, 580<br />
<strong>DO:</strong> 12799<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>
309900
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
MUCOPOLYSACCHARIDOSIS, TYPE II; MPS2
</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">
MPS II<br />
HUNTER SYNDROME<br />
IDURONATE 2-SULFATASE DEFICIENCY<br />
IDS DEFICIENCY<br />
SULFOIDURONATE SULFATASE DEFICIENCY<br />
SIDS DEFICIENCY
</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/X/783?start=-3&limit=10&highlight=783">
Xq28
</a>
</span>
</td>
<td>
<span class="mim-font">
Mucopolysaccharidosis II
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/309900"> 309900 </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">
IDS
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300823"> 300823 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/309900" 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/PS607014" 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')">
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<span class="sr-only">Toggle Dropdown</span>
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&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/309900" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/309900" 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">
- X-linked recessive <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845977&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845977</a>, <a href="https://bioportal.bioontology.org/search?q=C1279481&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1279481</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001419" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001419</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001419" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001419</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">
- Dwarfism, mild <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3151876&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3151876</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422065006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422065006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237836003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237836003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237837007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237837007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E34.31" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E34.31</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003510</a>]</span><br /> -
Adult height 120-150cm <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839692&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839692</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> Head </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Scaphocephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/109418001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">109418001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.01" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.01</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0265534&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265534</a>, <a href="https://bioportal.bioontology.org/search?q=C0432123&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0432123</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030799" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030799</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0004442" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004442</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030799" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030799</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=b49d4ad3bcb5a39e5263c4f1d7454a3e" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Dolichocephaly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=b49d4ad3bcb5a39e5263c4f1d7454a3e&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Macrocephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12138000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12138000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1145403003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1145403003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221355&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221355</a>, <a href="https://bioportal.bioontology.org/search?q=C2243051&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2243051</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000256</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001355</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000256</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=dd989bb153739761147ef05dc870b050" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Macrocephaly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=dd989bb153739761147ef05dc870b050&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Face </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Coarse facies <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845847&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845847</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000280</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000280</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Ears </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hearing loss <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/103276001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">103276001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/343087000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">343087000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15188001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15188001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H91.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H91.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/389.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/389" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011053&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011053</a>, <a href="https://bioportal.bioontology.org/search?q=C0018772&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018772</a>, <a href="https://bioportal.bioontology.org/search?q=C1384666&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1384666</a>, <a href="https://bioportal.bioontology.org/search?q=C3887873&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3887873</a>, <a href="https://bioportal.bioontology.org/search?q=C2029884&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2029884</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000365</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000365</a>]</span><br /> -
Recurrent otitis media <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0747085&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0747085</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000403" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000403</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000403" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000403</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- No corneal opacities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839693&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839693</a>]</span><br /> -
Papilledema <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/423341008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">423341008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248487006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248487006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/73221001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">73221001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H46.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H46.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.10</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/377.31" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.31</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/377.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/377.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0030353&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0030353</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001085" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001085</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001085" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001085</a>]</span><br /> -
Retinal pigmentation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151892&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151892</a>]</span><br /> -
Ptosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/11934000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">11934000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29696001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29696001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.409" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.409</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/374.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.3</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/374.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.30</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0005745&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0005745</a>, <a href="https://bioportal.bioontology.org/search?q=C0033377&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0033377</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Ptosis-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><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">
- Mucoid nasal discharge <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839694&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839694</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Mouth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Macroglossia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25273001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25273001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/270516002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">270516002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K14.8" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K14.8</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q38.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q38.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/750.15" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">750.15</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0024421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0024421</a>, <a href="https://bioportal.bioontology.org/search?q=C0009677&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009677</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000158" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000158</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000158" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000158</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=ac5acf24e74116d49a4df85084887155" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Tongue,Large-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=ac5acf24e74116d49a4df85084887155&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Full lips <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248177001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248177001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836543&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836543</a>, <a href="https://bioportal.bioontology.org/search?q=C0424485&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424485</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012471" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012471</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012471" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012471</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Teeth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Delayed tooth eruption <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/5639000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">5639000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239174&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239174</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000684" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000684</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000684" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000684</a>]</span><br /> -
Widely spaced teeth <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1844813&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1844813</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000687" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000687</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000687" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000687</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=5df0e44305e6ff6a9784b3b2408e902a" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Teeth,Widely_Spaced-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=5df0e44305e6ff6a9784b3b2408e902a&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Neck </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Short neck <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95427009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95427009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0521525&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0521525</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000470" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000470</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000470" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000470</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=5edf45ce6835f32360d28d26249e2531" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Neck,Short-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=5edf45ce6835f32360d28d26249e2531&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><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">
- Valvular heart disease <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/368009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">368009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018824&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018824</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001654" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001654</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001654" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001654</a>]</span><br /> -
Ischemic heart disease <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/297242006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">297242006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/414545008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">414545008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/414795007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">414795007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I20-I25" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I20-I25</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/410-414.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">410-414.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1313980&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1313980</a>, <a href="https://bioportal.bioontology.org/search?q=C0151744&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151744</a>]</span><br /> -
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> Airways </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Tracheobronchomalacia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/233788001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">233788001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0340231&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0340231</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002786" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002786</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002786" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002786</a>]</span><br /> -
Obstructive sleep apnea <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/78275009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">78275009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G47.33" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G47.33</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/327.23" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">327.23</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0520679&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0520679</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002870" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002870</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002870" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002870</a>]</span><br /> -
Asthma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/195967001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">195967001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/J45.909" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">J45.909</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/J45" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">J45</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/J45.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">J45.90</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/493.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">493.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/493" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">493</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0004096&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0004096</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002099" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002099</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002099" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002099</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> External Features </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Inguinal hernia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/396232000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">396232000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K40.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K40.90</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/550" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">550</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019294&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019294</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000023" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000023</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000023" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000023</a>]</span><br /> -
Umbilical hernia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/396347007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">396347007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K42" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K42</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K42.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K42.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/553.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">553.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019322&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019322</a>, <a href="https://bioportal.bioontology.org/search?q=C0041636&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0041636</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001537" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001537</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001537" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001537</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Liver </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hepatomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80515008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80515008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019209&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019209</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Spleen </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Splenomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16294009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16294009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038002&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038002</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001744" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001744</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001744" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001744</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Diarrhea <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267060006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267060006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/62315008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">62315008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R19.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R19.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/787.91" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.91</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011991&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011991</a>, <a href="https://bioportal.bioontology.org/search?q=C2169706&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2169706</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002014" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002014</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002014" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002014</a>]</span><br /> -
Intestinal pseudo-obstruction <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/235825006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">235825006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0021847&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0021847</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004389" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004389</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004389" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004389</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">
- Dysostosis multiplex <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/254069004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">254069004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5848292&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5848292</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000943" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000943</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000943" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000943</a>]</span><br />
</span>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Spine </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Kyphosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/71311003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">71311003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/414564002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">414564002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/413428007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">413428007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M40.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M40.20</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q76.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q76.41</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/737.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">737.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0265673&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265673</a>, <a href="https://bioportal.bioontology.org/search?q=C0022821&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022821</a>, <a href="https://bioportal.bioontology.org/search?q=C2115817&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2115817</a>, <a href="https://bioportal.bioontology.org/search?q=C0022822&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022822</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002808" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002808</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002808" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002808</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">
- Flexion contractures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/88565003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">88565003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/203598005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">203598005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/785817002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">785817002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/385522000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">385522000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M21.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M21.2</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M21.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M21.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0333068&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0333068</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001371" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001371</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001371" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001371</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Hands </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Claw hand <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/367393006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">367393006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/299034005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">299034005</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/736.06" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">736.06</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0158470&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0158470</a>, <a href="https://bioportal.bioontology.org/search?q=C5550991&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5550991</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Feet </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Pes cavus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/205091006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">205091006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/36755004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">36755004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86900005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86900005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/736.73" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">736.73</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/754.71" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.71</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0728829&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0728829</a>, <a href="https://bioportal.bioontology.org/search?q=C0039273&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0039273</a>, <a href="https://bioportal.bioontology.org/search?q=C2239098&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2239098</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001761" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001761</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001761" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001761</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=2ad12e53b20f47e5685234fa29da6610" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Pes_Cavus-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=2ad12e53b20f47e5685234fa29da6610&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><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">
- Pebbly skin lesions on back, upper arms, and thigh <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3806810&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3806810</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Hair </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hypertrichosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29966009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29966009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/271607001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">271607001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L68" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L68</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/L68.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L68.3</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/L68.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L68.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020555&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020555</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000998" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000998</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000998" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000998</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Neurodegeneration leading to profound mental retardation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839689&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839689</a>]</span><br /> -
Cervical cord compression <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0852866&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0852866</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002341" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002341</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002341" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002341</a>]</span><br /> -
Hydrocephalus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/230745008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">230745008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G91" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G91</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G91.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G91.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020255&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020255</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000238" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000238</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000238" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000238</a>]</span><br /> -
Normal intelligence in IIB <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839690&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839690</a>]</span><br /> -
Seizures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> VOICE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Hoarse voice <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/50219008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">50219008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R49.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R49.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019825&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019825</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001609" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001609</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001609" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001609</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Iduronate sulfatase deficiency in fibroblasts, amniocytes and white blood cells <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839695&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839695</a>]</span><br /> -
Dermatan and heparan sulfate excretion in urine <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839696&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839696</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Onset 2-4 years of age in IIA<br /> -
Two forms: IIA (severe) and IIB (mild)<br /> -
Death before age 15 in IIA<br /> -
Survival to 20s-60s in IIB<br /> -
Prenatal diagnosis available<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 iduronate-2-sulfatase gene (IDS, <a href="/entry/300823#0001">300823.0001</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>
Mucopolysaccharidoses
- <a href="/phenotypicSeries/PS607014">PS607014</a>
- 13 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/3/149?start=-3&limit=10&highlight=149"> 3p22.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/253010"> Mucopolysaccharidosis type IVB (Morquio) </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/253010"> 253010 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611458"> GLB1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611458"> 611458 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/337?start=-3&limit=10&highlight=337"> 3p21.31 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601492"> Mucopolysaccharidosis 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/601492"> 601492 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607071"> HYAL1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607071"> 607071 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/22?start=-3&limit=10&highlight=22"> 4p16.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607014"> Mucopolysaccharidosis Ih </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/607014"> 607014 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252800"> IDUA </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252800"> 252800 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/22?start=-3&limit=10&highlight=22"> 4p16.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607016"> Mucopolysaccharidosis Is </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/607016"> 607016 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252800"> IDUA </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252800"> 252800 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/22?start=-3&limit=10&highlight=22"> 4p16.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607015"> Mucopolysaccharidosis Ih/s </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/607015"> 607015 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252800"> IDUA </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252800"> 252800 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/282?start=-3&limit=10&highlight=282"> 5q14.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/253200"> Mucopolysaccharidosis type VI (Maroteaux-Lamy) </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/253200"> 253200 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611542"> ARSB </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611542"> 611542 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/330?start=-3&limit=10&highlight=330"> 5q15 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619698"> Mucopolysaccharidosis, 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/619698"> 619698 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610011"> ARSK </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610011"> 610011 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/297?start=-3&limit=10&highlight=297"> 7q11.21 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/253220"> Mucopolysaccharidosis 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/253220"> 253220 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611499"> GUSB </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611499"> 611499 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/8/244?start=-3&limit=10&highlight=244"> 8p11.21-p11.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252930"> Mucopolysaccharidosis type IIIC (Sanfilippo C) </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/252930"> 252930 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610453"> HGSNAT </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610453"> 610453 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/16/739?start=-3&limit=10&highlight=739"> 16q24.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/253000"> Mucopolysaccharidosis IVA </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/253000"> 253000 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612222"> GALNS </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612222"> 612222 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/579?start=-3&limit=10&highlight=579"> 17q21.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252920"> Mucopolysaccharidosis type IIIB (Sanfilippo B) </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/252920"> 252920 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609701"> NAGLU </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609701"> 609701 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/1017?start=-3&limit=10&highlight=1017"> 17q25.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252900"> Mucopolysaccharidosis type IIIA (Sanfilippo A) </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/252900"> 252900 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605270"> SGSH </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605270"> 605270 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/X/783?start=-3&limit=10&highlight=783"> Xq28 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/309900"> Mucopolysaccharidosis II </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/309900"> 309900 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300823"> IDS </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300823"> 300823 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
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<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
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<p>A number sign (#) is used with this entry because mucopolysaccharidosis type II (MPS2), also known as Hunter syndrome, is caused by mutation in the gene encoding iduronate 2-sulfatase (IDS; <a href="/entry/300823">300823</a>) on chromosome Xq28.</p>
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<p>Mucopolysaccharidosis II (MPS2) is a rare X-linked recessive disorder caused by deficiency of the lysosomal enzyme iduronate sulfatase, leading to progressive accumulation of glycosaminoglycans in nearly all cell types, tissues, and organs. Patients with MPS II excrete excessive amounts of chondroitin sulfate B (dermatan sulfate) and heparitin sulfate (heparan sulfate) in the urine (<a href="#55" class="mim-tip-reference" title="McKusick, V. A. &lt;strong&gt;The Mucopolysaccharidoses. Heritable Disorders of Connective Tissue. (4th ed.)&lt;/strong&gt; St. Louis: C. V. Mosby (pub.) 1972. Pp. 556-574."None>McKusick, 1972</a>; <a href="#101" class="mim-tip-reference" title="Wraith, J. E., Scarpa, M., Beck, M., Bodamer, O. A., De Meirleir, L., Guffon, N., Lund, A. M., Malm, G., Van der Ploeg, A. T., Zeman, J. &lt;strong&gt;Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy.&lt;/strong&gt; Europ. J. Pediat. 167: 267-277, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18038146/&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;18038146&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=18038146[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/10.1007/s00431-007-0635-4&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="18038146">Wraith et al., 2008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18038146" 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>
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<p>MPS II is a multisystem disorder. Clinical manifestations include severe airway obstruction, skeletal deformities, cardiomyopathy, and, in most patients, neurologic decline. Death usually occurs in the second decade of life, although some patients with less severe disease have survived into their fifth or sixth decade (summary by <a href="#101" class="mim-tip-reference" title="Wraith, J. E., Scarpa, M., Beck, M., Bodamer, O. A., De Meirleir, L., Guffon, N., Lund, A. M., Malm, G., Van der Ploeg, A. T., Zeman, J. &lt;strong&gt;Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy.&lt;/strong&gt; Europ. J. Pediat. 167: 267-277, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18038146/&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;18038146&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=18038146[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/10.1007/s00431-007-0635-4&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="18038146">Wraith et al., 2008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18038146" 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="#55" class="mim-tip-reference" title="McKusick, V. A. &lt;strong&gt;The Mucopolysaccharidoses. Heritable Disorders of Connective Tissue. (4th ed.)&lt;/strong&gt; St. Louis: C. V. Mosby (pub.) 1972. Pp. 556-574."None>McKusick (1972)</a> recognized 2 clinically distinguishable forms of MPS II: a severe form (called MPS IIA) with progressive mental retardation and physical disability and death before age 15 years in most cases, and a mild form (called MPS IIB; see later) compatible with survival to adulthood in which reproduction is known to have occurred (<a href="#28" class="mim-tip-reference" title="DiFerrante, N. M., Nichols, B. L., Jr. &lt;strong&gt;A case of the Hunter syndrome with progeny.&lt;/strong&gt; Johns Hopkins Med. J. 130: 325-328, 1972.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4622960/&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;4622960&lt;/a&gt;]" pmid="4622960">DiFerrante and Nichols, 1972</a>) and in which intellect is impaired minimally, if at all. <a href="#55" class="mim-tip-reference" title="McKusick, V. A. &lt;strong&gt;The Mucopolysaccharidoses. Heritable Disorders of Connective Tissue. (4th ed.)&lt;/strong&gt; St. Louis: C. V. Mosby (pub.) 1972. Pp. 556-574."None>McKusick (1972)</a> noted a lack of corneal clouding in the X-linked form of MPS as opposed to the autosomal forms (see MPS I-H, <a href="/entry/607014">607014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4622960" 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="#101" class="mim-tip-reference" title="Wraith, J. E., Scarpa, M., Beck, M., Bodamer, O. A., De Meirleir, L., Guffon, N., Lund, A. M., Malm, G., Van der Ploeg, A. T., Zeman, J. &lt;strong&gt;Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy.&lt;/strong&gt; Europ. J. Pediat. 167: 267-277, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18038146/&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;18038146&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=18038146[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/10.1007/s00431-007-0635-4&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="18038146">Wraith et al. (2008)</a> stated that MPS II should be regarded as a continuum between 2 extremes (severe and attenuated). They noted that although the clinical course for the more severely affected patients is relatively predictable, there is considerable variability in the clinical phenotype and progression of the more attenuated form of the disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18038146" 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="Danes, B. S., Bearn, A. G. &lt;strong&gt;Hurler&#x27;s syndrome: demonstration of an inherited disorder of connective tissue in cell culture.&lt;/strong&gt; Science 149: 987-989, 1965.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4953285/&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;4953285&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/science.149.3687.987&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="4953285">Danes and Bearn (1965)</a> found that fibroblasts from patients with this disorder show metachromatic cytoplasmic inclusions and that about half the fibroblasts of heterozygotes show such inclusions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4953285" 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="#71" class="mim-tip-reference" title="Sapadin, A. N., Friedman, I. S. &lt;strong&gt;Extensive Mongolian spots associated with Hunter syndrome.&lt;/strong&gt; J. Am. Acad. Derm. 39: 1013-1015, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9843019/&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;9843019&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0190-9622(98)70280-4&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="9843019">Sapadin and Friedman (1998)</a> noted extensive Mongolian spots in a 4.5-year-old African American boy with Hunter syndrome. These patches were present at birth over the buttocks and lumbar sacral area. Other patches continued to appear over the paraspinal area of the entire back, and smaller lesions occurred on the anterior trunk. 'Pebbly' skin first appeared on the proximal arms, soon after became visible on the scapulas and thighs, and later in the pectoral areas. The other features were typical of Hunter syndrome, which was confirmed by enzyme assay. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9843019" 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="#63" class="mim-tip-reference" title="Ochiai, T., Ito, K., Okada, T., Chin, M., Shichino, H., Mugishima, H. &lt;strong&gt;Significance of extensive Mongolian spots in Hunter&#x27;s syndrome.&lt;/strong&gt; Brit. J. Derm. 148: 1173-1178, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12828746/&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;12828746&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1046/j.1365-2133.2003.05317.x&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="12828746">Ochiai et al. (2003)</a> investigated the occurrence of Mongolian spots in 7 Japanese infants with Hunter syndrome before and after hematopoietic stem cell transplantation (HSCT). Pre-HSCT observation revealed that all the patients had extensive Mongolian spots that were present at birth and showed no signs of resolution during the post-HSCT period. Electron microscopic findings showed that pigment-bearing dermal melanocytes contained many free melanosomes in stage IV. These were surrounded by extracellular sheaths and encircled by elastic fibers. The results of <a href="#63" class="mim-tip-reference" title="Ochiai, T., Ito, K., Okada, T., Chin, M., Shichino, H., Mugishima, H. &lt;strong&gt;Significance of extensive Mongolian spots in Hunter&#x27;s syndrome.&lt;/strong&gt; Brit. J. Derm. 148: 1173-1178, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12828746/&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;12828746&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1046/j.1365-2133.2003.05317.x&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="12828746">Ochiai et al. (2003)</a> indicated a strong clinical correlation between extensive Mongolian spots and Hunter syndrome, and ultrastructural findings suggested that the hyperpigmentation is a long-lasting symptom. <a href="#63" class="mim-tip-reference" title="Ochiai, T., Ito, K., Okada, T., Chin, M., Shichino, H., Mugishima, H. &lt;strong&gt;Significance of extensive Mongolian spots in Hunter&#x27;s syndrome.&lt;/strong&gt; Brit. J. Derm. 148: 1173-1178, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12828746/&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;12828746&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1046/j.1365-2133.2003.05317.x&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="12828746">Ochiai et al. (2003)</a> concluded that recognition of extensive Mongolian spots is essential as it may lead to early diagnosis in patients with mild forms of Hunter syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12828746" 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="#39" class="mim-tip-reference" title="Huang, C.-T., Chu, S.-Y., Lee, Y.-C. &lt;strong&gt;Optical coherence tomography of chorioretinopathy caused by mucopolysaccharidoses.&lt;/strong&gt; Ophthalmology 122: 1535-1537, 2015.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25864794/&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;25864794&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ophtha.2015.01.015&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="25864794">Huang et al. (2015)</a> described chorioretinopathy in 5 patients with Hunter syndrome. In 2 patients (aged 9 and 20 years) with multifocal depigmented retinopathy, spectral-domain optical coherence tomography (SD-OCT) showed focal choroidal thinning in the pigmentary retinopathy areas. A mild, fuzzy, and thickened external limiting membrane (ELM), widening of the distance between the retinal pigment epithelium and ellipsoid zone at the fovea, and disruption of the ellipsoid zone at the extrafoveal area were also noted. In an 18-year-old man with a history of retinoschisis, SD-OCT showed mild retinal folds, a fuzzy and thickened ELM at the fovea, and some small cystic changes. In 2 patients (aged 10 and 14 years) with retinopathy resembling retinitis pigmentosa, SD-OCT showed some cystic spaces, a fuzzy ELM, disrupted ellipsoid zone, and diffuse loss of choriocapillaris. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25864794" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Attenuated Mucopolysaccharidosis Type II (MPS IIB)</em></strong></p><p>
<a href="#37" class="mim-tip-reference" title="Hobolth, N., Pedersen, C. &lt;strong&gt;Six cases of a mild form of the Hunter syndrome in five generations: three affected males with progeny. (Abstract)&lt;/strong&gt; Clin. Genet. 13: 121 only, 1978."None>Hobolth and Pedersen (1978)</a> described a kindred with 6 cases of mild Hunter syndrome additionally remarkable for survival to ages 65 and 87 in 2 of the cases and for progeny from 3 affected males.</p><p><a href="#86" class="mim-tip-reference" title="Tsuzaki, S., Matsuo, N., Nagai, T., Osano, M., Orii, T. &lt;strong&gt;An unusually mild variant of Hunter&#x27;s syndrome in a 14-year-old boy: normal growth and development.&lt;/strong&gt; Acta Paediat. Scand. 76: 844-846, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3116824/&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;3116824&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1651-2227.1987.tb10577.x&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="3116824">Tsuzaki et al. (1987)</a> described an unusually mild form of Hunter syndrome. At 14 years of age, their patient had normal growth and development. He had mild dysostosis radiologically, coarse facial features, flexion contractures of the elbows and shoulder joints, and moderate hepatosplenomegaly. At age 8 he had the murmur of aortic regurgitation, and at age 12 angiocardiography was said to have shown grade 4 aortic regurgitation. The mother was a healthy carrier. <a href="#4" class="mim-tip-reference" title="Ballenger, C. E., Swift, T. R., Leshner, R. T., El Gammal, T. A., McDonald, T. F. &lt;strong&gt;Myelopathy in mucopolysaccharidosis type II (Hunter syndrome).&lt;/strong&gt; Ann. Neurol. 7: 382-385, 1980.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6769383/&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;6769383&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.410070418&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="6769383">Ballenger et al. (1980)</a> described spastic quadriplegia in a 24-year-old man due to impingement of the thickened meninges on the cervical spinal cord. Tracheal narrowing required tracheostomy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6769383+3116824" 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="#105" class="mim-tip-reference" title="Yund, B., Rudser, K., Ahmed, A., Kovac, V., Nestrasil, I., Raiman, J., Mamak, E., Harmatz, P., Steiner, R., Lau, H., Vekaria, P., Wozniak, J. R., Lim, K. O., Delaney, K., Whitley, C., Shapiro, E. G. &lt;strong&gt;Cognitive, medical, and neuroimaging characteristics of attenuated mucopolysaccharidosis type II.&lt;/strong&gt; Molec. Genet. Metab. 114: 170-177, 2015.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25541100/&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;25541100&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=25541100[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/10.1016/j.ymgme.2014.12.299&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="25541100">Yund et al. (2015)</a> studied the association of brain volumes and somatic disease burden with neuropsychologic outcomes, including measures of intelligence, memory, and attention in 20 patients with attenuated MPS II with a mean age of 15.8 years. MRI volumes were compared to 55 normal controls. IQ and memory were average, but measures of attention were 1 SD below the average range. Corpus callosum volumes were significantly different from age-matched controls, differing by 22%. Normal age-related volume increases in white matter were not seen in MPS II patients as they were in controls. Somatic disease burden and white matter and corpus callosum volumes were significantly associated with attention deficits. Neither age at evaluation nor age at starting treatment predicted attention outcomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25541100" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Clinical Variability</em></strong></p><p>
Patients with complete deletion of the IDS locus often have atypical phenotypes, including ptosis, obstructive sleep apnea, and seizures (<a href="#100" class="mim-tip-reference" title="Wraith, J. E., Cooper, A., Thornley, M., Wilson, P. J., Nelson, P. V., Morris, C. P., Hopwood, J. J. &lt;strong&gt;The clinical phenotype of two patients with a complete deletion of the iduronate-2-sulphatase gene (mucopolysaccharidosis II--Hunter syndrome).&lt;/strong&gt; Hum. Genet. 87: 205-206, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1906048/&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;1906048&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00204183&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="1906048">Wraith et al., 1991</a>; <a href="#29" class="mim-tip-reference" title="Froissart, R., Blond, J.-L., Maire, I., Guibaud, P., Hopwood, J. J., Mathieu, M., Bozon, D. &lt;strong&gt;Hunter syndrome: gene deletions and rearrangements.&lt;/strong&gt; Hum. Mutat. 2: 138-140, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8318991/&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;8318991&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.1380020214&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="8318991">Froissart et al., 1993</a>). <a href="#75" class="mim-tip-reference" title="Steen-Bondeson, M.-L., Dahl, N., Tonnesen, T., Kleijer, W. J., Seidlitz, G., Gustavson, K.-H., Wilson, P. J., Morris, C. P., Hopwood, J. J., Pettersson, U. &lt;strong&gt;Molecular analysis of patients with Hunter syndrome: implication of a region prone to structural alterations within the IDS gene.&lt;/strong&gt; Hum. Molec. Genet. 1: 195-198, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1303177/&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;1303177&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/1.3.195&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="1303177">Steen-Bondeson et al. (1992)</a> and others have suggested that some of these atypical features in Hunter syndrome patients may be caused by deletion of additional genes in the region of IDS; see MOLECULAR GENETICS section. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1303177+1906048+8318991" 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>
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<a id="inheritance" class="mim-anchor"></a>
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<strong>Inheritance</strong>
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<p>Hunter syndrome is an X-linked recessive disorder (<a href="#55" class="mim-tip-reference" title="McKusick, V. A. &lt;strong&gt;The Mucopolysaccharidoses. Heritable Disorders of Connective Tissue. (4th ed.)&lt;/strong&gt; St. Louis: C. V. Mosby (pub.) 1972. Pp. 556-574."None>McKusick, 1972</a>). The disorder is expected to be found only in males, but some females have been reported.</p><p><a href="#13" class="mim-tip-reference" title="Broadhead, D. M., Kirk, J. M., Burt, A. J., Gupta, V., Ellis, P. M., Besley, G. T. N. &lt;strong&gt;Full expression of Hunter&#x27;s disease in a female with an X-chromosome deletion leading to non-random inactivation.&lt;/strong&gt; Clin. Genet. 30: 392-398, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3100113/&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;3100113&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1986.tb01896.x&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="3100113">Broadhead et al. (1986)</a> described a 2.5-year-old girl with typical full expression of MPS II. Chromosome studies showed partial deletion of the long arm of one X chromosome; band Xq25 was thought to be missing. Studies using BrdU indicated that the deleted X chromosome was consistently late replicating and, as a result, the Hunter gene presumed to be present on the other X chromosome was fully expressed. There were no other cases of Hunter syndrome known in the family; however, the mother had a partial deficiency (43%) of serum iduronate-2-sulfate sulfatase. The father's serum enzyme activity was in the control range. Hence, caution must obviously be exercised in interpreting the findings of X/autosome translocations as indication of an X-linked trait at the site of the breakpoint on the X chromosome, when there is no way to identify carrier status in the mother. In such instances, the full expression of the disorder in a female may merely be the result of nonrandom inactivation of the abnormal X chromosome uncovering the mutant gene on the other X chromosome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3100113" 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="Clarke, J. T. R., Pearce, R. D., Greer, W. L., Strasberg, P., Ray, P. N. &lt;strong&gt;Hunter disease (MPS, type II) in a karyotypically normal girl associated with selective X-chromosome inactivation. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 47 (suppl.): A52 only, 1990."None>Clarke et al. (1990)</a> described clinically and biochemically typical Hunter syndrome in a karyotypically normal girl. Cross-correction with fibroblasts of a classic male patient did not occur. In a second report, <a href="#20" class="mim-tip-reference" title="Clarke, J. T. R., Pearce, R. D., Greer, W. L., Strasberg, P., Ray, P. N. &lt;strong&gt;Hunter disease (MPS, type II) in a karyotypically normal girl associated with selective X-chromosome inactivation. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 47 (suppl.): A52 only, 1990."None>Clarke et al. (1990)</a> presented evidence they interpreted as indicating that in this patient the maternal X chromosome was selectively inactivated, whereas presumably the paternal X chromosome carried a mutation for this disorder. The critical evidence was provided by somatic cell hybrid clones produced by fusion of the patient's fibroblasts with HPRT-negative hamster fibroblasts and grown in HAT-ouabain medium to select for hybrids containing at least one active human X chromosome. <a href="#19" class="mim-tip-reference" title="Clarke, J. T. R., Greer, W. L., Strasberg, P. M., Pearce, R. D., Skomorowski, M. A., Ray, P. N. &lt;strong&gt;Hunter disease (mucopolysaccharidosis type II) associated with unbalanced inactivation of the X chromosomes in a karyotypically normal girl.&lt;/strong&gt; Am. J. Hum. Genet. 49: 289-297, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1678247/&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;1678247&lt;/a&gt;]" pmid="1678247">Clarke et al. (1991)</a> presented further evidence in support of this hypothesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1678247" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Clarke, J. T. R., Wilson, P. J., Morris, C. P., Hopwood, J. J., Richards, R. I., Sutherland, G. R., Ray, P. N. &lt;strong&gt;Characterization of a deletion at Xq27-q28 associated with unbalanced inactivation of the nonmutant X chromosome.&lt;/strong&gt; Am. J. Hum. Genet. 51: 316-322, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1642233/&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;1642233&lt;/a&gt;]" pmid="1642233">Clarke et al. (1992)</a> reported molecular characterization of the mutation associated with marked unbalanced expression of the mutant X chromosome in the karyotypically normal girl with Hunter syndrome reported by Clarke et al. (<a href="#20" class="mim-tip-reference" title="Clarke, J. T. R., Pearce, R. D., Greer, W. L., Strasberg, P., Ray, P. N. &lt;strong&gt;Hunter disease (MPS, type II) in a karyotypically normal girl associated with selective X-chromosome inactivation. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 47 (suppl.): A52 only, 1990."None>1990</a>, <a href="#19" class="mim-tip-reference" title="Clarke, J. T. R., Greer, W. L., Strasberg, P. M., Pearce, R. D., Skomorowski, M. A., Ray, P. N. &lt;strong&gt;Hunter disease (mucopolysaccharidosis type II) associated with unbalanced inactivation of the X chromosomes in a karyotypically normal girl.&lt;/strong&gt; Am. J. Hum. Genet. 49: 289-297, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1678247/&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;1678247&lt;/a&gt;]" pmid="1678247">1991</a>). Southern analysis of DNA extracted from somatic cell hybrids containing only the mutant X chromosome showed deletion of several Xq27.3-q28 loci including FRAXA (<a href="/entry/309550">309550</a>) and the 3-prime end of the IDS gene. Three flanking loci, including DXS52, were intact. On the basis of these results, <a href="#22" class="mim-tip-reference" title="Clarke, J. T. R., Wilson, P. J., Morris, C. P., Hopwood, J. J., Richards, R. I., Sutherland, G. R., Ray, P. N. &lt;strong&gt;Characterization of a deletion at Xq27-q28 associated with unbalanced inactivation of the nonmutant X chromosome.&lt;/strong&gt; Am. J. Hum. Genet. 51: 316-322, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1642233/&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;1642233&lt;/a&gt;]" pmid="1642233">Clarke et al. (1992)</a> concluded that the mutation was a simple deletion extending a maximum of 3-5 cM to the centromeric side of the IDS gene. Their studies indicated that the telomeric terminus of the deletion was located near the middle of the coding sequence of the gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1678247+1642233" 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="#99" class="mim-tip-reference" title="Winchester, B., Young, E., Geddes, S., Genet, S., Hurst, J., Middleton-Price, H., Williams, N., Webb, M., Habel, A., Malcolm, S. &lt;strong&gt;Female twin with Hunter disease due to nonrandom inactivation of the X-chromosome: a consequence of twinning.&lt;/strong&gt; Am. J. Med. Genet. 44: 834-838, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1481858/&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;1481858&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320440625&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="1481858">Winchester et al. (1992)</a> reported the occurrence of Hunter syndrome in a karyotypically normal girl who was 1 of identical twins. Molecular studies showed nonrandom X inactivation in both her fibroblasts and her lymphocytes, while her normal twin showed equal usage of the 2 X chromosomes. In view of previous reports of 7 pairs of identical female twins in which 1 had Duchenne muscular dystrophy, <a href="#99" class="mim-tip-reference" title="Winchester, B., Young, E., Geddes, S., Genet, S., Hurst, J., Middleton-Price, H., Williams, N., Webb, M., Habel, A., Malcolm, S. &lt;strong&gt;Female twin with Hunter disease due to nonrandom inactivation of the X-chromosome: a consequence of twinning.&lt;/strong&gt; Am. J. Med. Genet. 44: 834-838, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1481858/&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;1481858&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320440625&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="1481858">Winchester et al. (1992)</a> suggested that twinning may be strongly associated with nonrandom X inactivation. In some cases of twins discordant for DMD, symmetric nonrandom X inactivation was found with each twin showing a nonrandom pattern but in opposite directions. In at least one case (<a href="#53" class="mim-tip-reference" title="Lupski, J. R., Garcia, C. A., Zoghbi, H. Y., Hoffman, E. P., Fenwick, R. G. &lt;strong&gt;Discordance of muscular dystrophy in monozygotic female twins: evidence supporting asymmetric splitting of the inner cell mass in a manifesting carrier of Duchenne dystrophy.&lt;/strong&gt; Am. J. Med. Genet. 40: 354-364, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1683155/&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;1683155&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320400323&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="1683155">Lupski et al., 1991</a>), however, 1 girl showed an apparently random pattern and the affected girl a nonrandom pattern. The patient with Hunter syndrome reported by <a href="#99" class="mim-tip-reference" title="Winchester, B., Young, E., Geddes, S., Genet, S., Hurst, J., Middleton-Price, H., Williams, N., Webb, M., Habel, A., Malcolm, S. &lt;strong&gt;Female twin with Hunter disease due to nonrandom inactivation of the X-chromosome: a consequence of twinning.&lt;/strong&gt; Am. J. Med. Genet. 44: 834-838, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1481858/&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;1481858&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320440625&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="1481858">Winchester et al. (1992)</a> was of the latter type. <a href="#34" class="mim-tip-reference" title="Goldenfum, S. L., Young, E., Michelakakis, H., Tsagarakis, S., Winchester, B. &lt;strong&gt;Mutation analysis in 20 patients with Hunter disease.&lt;/strong&gt; Hum. Mutat. 7: 76-78, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8664909/&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;8664909&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1098-1004(1996)7:1&lt;76::AID-HUMU14&gt;3.0.CO;2-P&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="8664909">Goldenfum et al. (1996)</a> demonstrated that both twins reported by <a href="#99" class="mim-tip-reference" title="Winchester, B., Young, E., Geddes, S., Genet, S., Hurst, J., Middleton-Price, H., Williams, N., Webb, M., Habel, A., Malcolm, S. &lt;strong&gt;Female twin with Hunter disease due to nonrandom inactivation of the X-chromosome: a consequence of twinning.&lt;/strong&gt; Am. J. Med. Genet. 44: 834-838, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1481858/&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;1481858&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320440625&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="1481858">Winchester et al. (1992)</a> were heterozygous for a 1-bp deletion of cytosine at position 123 of their cDNA. The asymptomatic cotwin showed random X inactivation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8664909+1683155+1481858" 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 analyzing 5 samples of families with MPS II, with a total of 158 cases, <a href="#54" class="mim-tip-reference" title="Machill, G., Barbujani, G., Danieli, G. A., Herrmann, F. H. &lt;strong&gt;Segregation and sporadic cases in families with Hunter&#x27;s syndrome.&lt;/strong&gt; J. Med. Genet. 28: 398-401, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1908009/&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;1908009&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.28.6.398&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="1908009">Machill et al. (1991)</a> found that the mutant allele segregated in agreement with mendelian expectations for an X-linked recessive disorder, but the proportion of sporadic cases was significantly lower than expected under mutation-selection equilibrium. Heterogeneity among the samples was evident but was caused entirely by a sample of Ashkenazi families, in which the segregation pattern had previously been interpreted as suggesting prenatal selection in favor of the pathologic allele. In their analysis of the 5 samples by a maximum likelihood approach, <a href="#54" class="mim-tip-reference" title="Machill, G., Barbujani, G., Danieli, G. A., Herrmann, F. H. &lt;strong&gt;Segregation and sporadic cases in families with Hunter&#x27;s syndrome.&lt;/strong&gt; J. Med. Genet. 28: 398-401, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1908009/&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;1908009&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.28.6.398&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="1908009">Machill et al. (1991)</a> found no suggestion of segregation distortion. The apparent deficiency of sporadic cases might be due to ascertainment bias. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1908009" 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 Ashkenazi Jews in Israel, <a href="#109" class="mim-tip-reference" title="Zlotogora, J., Schaap, T., Zeigler, M., Bach, G. &lt;strong&gt;Hunter syndrome among Ashkenazi Jews in Israel; evidence for prenatal selection favoring the Hunter allele.&lt;/strong&gt; Hum. Genet. 71: 329-332, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3935563/&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;3935563&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00388459&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="3935563">Zlotogora et al. (1985)</a> found no new mutations among the mothers of probands. Furthermore, they found a striking deviation in segregation of the Hunter and normal alleles in heterozygous females, with favoring of the former. In non-Ashkenazi populations, the rate of new mutations and the segregation ratio have been close to those expected (<a href="#1" class="mim-tip-reference" title="Archer, I. M., Young, I. D., Rees, D. W., Oladimeji, A., Wusteman, F. S., Harper, P. S. &lt;strong&gt;Carrier detection in Hunter syndrome.&lt;/strong&gt; Am. J. Med. Genet. 16: 61-69, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6227239/&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;6227239&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320160111&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="6227239">Archer et al., 1983</a>; <a href="#85" class="mim-tip-reference" title="Tonnesen, T. &lt;strong&gt;The use of fructose 1-phosphate to detect Hunter heterozygotes in fibroblast cultures from high-risk carriers.&lt;/strong&gt; Hum. Genet. 66: 212-216, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6425196/&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;6425196&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00286603&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="6425196">Tonnesen, 1984</a>). <a href="#110" class="mim-tip-reference" title="Zlotogora, J., Schaap, T., Zeigler, M., Bach, G. &lt;strong&gt;Hunter syndrome in Jews in Israel: further evidence for prenatal selection favoring the Hunter allele.&lt;/strong&gt; Hum. Genet. 86: 531-533, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1901828/&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;1901828&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00194650&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="1901828">Zlotogora et al. (1991)</a> reported that 10 of the 12 Jewish families with Hunter syndrome in Israel were of Ashkenazi or Moroccan origin. They provided further evidence that in these families there is a paucity of new mutations and they confirmed the significant deviation of the segregation ratio between the Hunter gene and the normal allele among the offspring of heterozygous mothers and among the sibs of affected children. Selection in favor of the X chromosome carrying the Hunter allele was suggested. It has apparently not been observed in other ethnic groups. The explanation may lie in another closely linked gene such that the phenomenon is particular to the Jewish population. Another possibility is that the mutation itself gives an advantage to that chromosome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1901828+3935563+6227239+6425196" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Froissart, R., Maire, I., Bonnet, V., Levade, T., Bozon, D. &lt;strong&gt;Germline and somatic mosaicism in a female carrier of Hunter disease.&lt;/strong&gt; J. Med. Genet. 34: 137-140, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9039991/&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;9039991&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.34.2.137&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="9039991">Froissart et al. (1997)</a> found evidence of germline and somatic mosaicism in the mother of a boy with an arg443-to-ter mutation (<a href="/entry/300823#0001">300823.0001</a>). The mutation was found in a varying proportion of tissues tested (7% in leukocytes, lymphocytes and lymphoblastoid cells, and 22% in fibroblasts). The proband's sister carried the 'at risk' allele (as determined by haplotype analysis), but not the mutation. In sporadic cases of X-linked diseases, germline mosaicism of the proband's mother is difficult to exclude and should be considered in genetic counseling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9039991" 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="#76" class="mim-tip-reference" title="Sukegawa, K., Matsuzaki, T., Fukuda, S., Masuno, M., Fukao, T., Kokuryu, M., Iwata, S., Tomatsu, S., Orii, T., Kondo, N. &lt;strong&gt;Brother/sister siblings affected with Hunter disease: evidence for skewed X chromosome inactivation.&lt;/strong&gt; Clin. Genet. 53: 96-101, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9611068/&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;9611068&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1998.tb02654.x&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="9611068">Sukegawa et al. (1998)</a> reported a brother/sister pair with Hunter syndrome. Both had normal karyotypes. The sister was heterozygous for the R468L mutation (<a href="/entry/300823#0015">300823.0015</a>) in genomic DNA, but homozygous for the allele in fibroblasts and lymphoblasts, resulting in relatively severe manifestations of the disease. Analysis of methylation patterns of the androgen receptor gene showed skewed X-chromosome inactivation of the paternal allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9611068" 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>
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<p><a href="#6" class="mim-tip-reference" title="Berg, K., Danes, B. S., Bearn, A. G. &lt;strong&gt;The linkage relation of the loci for the Xm serum system and the X-linked form of Hurler&#x27;s syndrome (Hunter&#x27;s syndrome).&lt;/strong&gt; Am. J. Hum. Genet. 20: 398-401, 1968.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4969416/&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;4969416&lt;/a&gt;]" pmid="4969416">Berg et al. (1968)</a> concluded that the Hunter locus and the Xm locus (<a href="/entry/314900">314900</a>) are within measurable distance of each other on Xq28, the best estimate of the recombination fraction being 0.09. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4969416" 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="#57" class="mim-tip-reference" title="Mossman, J., Blunt, S., Stephens, R., Jones, E. E., Pembrey, M. &lt;strong&gt;Hunter&#x27;s disease in a girl: association with X:5 chromosomal translocation disrupting the Hunter gene.&lt;/strong&gt; Arch. Dis. Child. 58: 911-915, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6418082/&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;6418082&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/adc.58.11.911&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="6418082">Mossman et al. (1983)</a> described a 3-year-old girl with typical Hunter syndrome. She had an apparently balanced reciprocal translocation between chromosomes X and 5 with the break in the former being between q26 and q27. The parents' karyotypes were normal. Pedigree analysis and normal enzyme levels in the mother's fibroblasts, serum, and hair roots indicated that the child had a new mutation. Location of the Hunter gene in the q26-q27 region and disruption of this gene in the origination of the translocation in this girl was proposed. The principle here is the same as that used to assign regionally the DMD locus (<a href="/entry/300377">300377</a>) and several others; the translocation chromosome is presumably the active one. Roberts et al. (<a href="#68" class="mim-tip-reference" title="Roberts, S. H., Upadhyaya, M., Sarfarazi, M., Harper, P. S. &lt;strong&gt;Further evidence localizing the gene for Hunter syndrome to the most distal band of the X chromosome long arm. (Abstract)&lt;/strong&gt; Cytogenet. Cell Genet. 46: 682 only, 1987."None>1987</a>, <a href="#69" class="mim-tip-reference" " title="Roberts, S. H., Upadhyaya, M., Sarfarazi, M., Harper, P. S. &lt;strong&gt;Further evidence localising the gene for Hunter syndrome to Xq28. (Abstract)&lt;/strong&gt; J. Med. Genet. 25: 280 only, 1988."None>1988</a>, <a href="#70" class="mim-tip-reference" title="Roberts, S. H., Upadhyaya, M., Sarfarazi, M., Harper, P. S. &lt;strong&gt;Further evidence localising the gene for Hunter&#x27;s syndrome to the distal region of the X chromosome long arm.&lt;/strong&gt; J. Med. Genet. 26: 309-313, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2499679/&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;2499679&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.26.5.309&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="2499679">1989</a>) reexamined the case of <a href="#57" class="mim-tip-reference" title="Mossman, J., Blunt, S., Stephens, R., Jones, E. E., Pembrey, M. &lt;strong&gt;Hunter&#x27;s disease in a girl: association with X:5 chromosomal translocation disrupting the Hunter gene.&lt;/strong&gt; Arch. Dis. Child. 58: 911-915, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6418082/&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;6418082&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/adc.58.11.911&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="6418082">Mossman et al. (1983)</a> cytogenetically and concluded that the breakpoint was in Xq28 rather than being more proximal, as previously suggested. This finding is more in keeping with the linkage studies with DNA markers, which suggest location of the locus at Xq28. Furthermore, replication studies indicated that the normal X in this patient was preferentially inactivated. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2499679+6418082" 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="#18" class="mim-tip-reference" title="Chase, D. S., Morris, A. H., Ballabio, A., Pepper, S., Giannelli, F., Adinolfi, M. &lt;strong&gt;Genetics of Hunter syndrome: carrier detection, new mutations, segregation and linkage analysis.&lt;/strong&gt; Ann. Hum. Genet. 50: 349-360, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3126700/&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;3126700&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1469-1809.1986.tb01756.x&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="3126700">Chase et al. (1986)</a> concluded that the Hunter locus is distal to the factor IX locus (<a href="/entry/300746">300746</a>) inasmuch as the maximum lod score for the linkage of these loci was 0.424 at theta = 0.25, whereas that for the linkage of the Hunter syndrome and DX13 was 3.01 at theta = 0.1. DX13 maps to Xq28. From studies with DNA probes, Upadhyaya et al. (<a href="#87" class="mim-tip-reference" title="Upadhyaya, M., Bamforth, S., Harper, P. S., Sarfarazi, M., Thomas, N. S. T., Shaw, D. J., Meredith, A. L., Rees, D., Davies, K., Young, I. D. &lt;strong&gt;Localization of Hunter syndrome gene by genetic linkage analysis. (Abstract)&lt;/strong&gt; Cytogenet. Cell Genet. 40: 765 only, 1985."None>1985</a>, <a href="#89" class="mim-tip-reference" title="Upadhyaya, M., Sarfarazi, M., Bamforth, J. S., Thomas, N. S. T., Oberle, I., Young, I., Harper, P. S. &lt;strong&gt;Localisation of the gene for Hunter syndrome on the long arm of X chromosome.&lt;/strong&gt; Hum. Genet. 74: 391-398, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2878868/&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;2878868&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00280492&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="2878868">1986</a>) suggested that the Hunter locus may be close to that for the fragile site at Xq27. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2878868+3126700" 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="#49" class="mim-tip-reference" title="Le Guern, E., Couillin, P., Oberle, I., Ravise, N., Boue, J. &lt;strong&gt;More precise localization of the gene for Hunter syndrome.&lt;/strong&gt; Genomics 7: 358-362, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2114352/&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;2114352&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0888-7543(90)90169-u&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="2114352">Le Guern et al. (1990)</a> did a family linkage study using 4 polymorphic markers from the Xq27-q28 region. A maximum lod score of 6.57 at theta = 0.0 was obtained with DXS304. Furthermore, they showed, consistent with the finding of others, that the breakpoint of the X;5 translocation described by <a href="#57" class="mim-tip-reference" title="Mossman, J., Blunt, S., Stephens, R., Jones, E. E., Pembrey, M. &lt;strong&gt;Hunter&#x27;s disease in a girl: association with X:5 chromosomal translocation disrupting the Hunter gene.&lt;/strong&gt; Arch. Dis. Child. 58: 911-915, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6418082/&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;6418082&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/adc.58.11.911&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="6418082">Mossman et al. (1983)</a> is distal to DXS98 and proximal to DXS304. <a href="#79" class="mim-tip-reference" title="Thomas, N. S. T., Roberts, S. H., Upadhyaya, M., Knight, S., Harper, P. S. &lt;strong&gt;Physical localization of the X;autosomal translocation breakpoint from a girl expressing Hunter syndrome using Xq27-q28 DNA markers. (Abstract)&lt;/strong&gt; Cytogenet. Cell Genet. 51: 1090 only, 1989."None>Thomas et al. (1989)</a> extended studies of the X;5 translocation by study of cell hybrids containing the derivative X as their only human X chromosome material. By study of DNA markers and of a hybrid clone that apparently had undergone a secondary DNA rearrangement, they concluded that the 'IDS and FRAXA are probably located in the same subregion around Xq27.3.' <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2114352+6418082" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Couillin, P., Le Guern, E., Ravise, N., Grisard, M.-C., Oostra, B. A., Boue, A. &lt;strong&gt;Strategy for constructing somatic hybrids isolating the two derivative chromosomes in X;autosome translocations: application to a female patient t(X;5) with Hunter syndrome.&lt;/strong&gt; Ann. Genet. 33: 196-207, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2128908/&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;2128908&lt;/a&gt;]" pmid="2128908">Couillin et al. (1990)</a> described a method for isolating the 2 X;5 translocated derivative chromosomes in separate rodent-human cell hybrids. The method was based mainly on immunofluorescent screening using MIC2 (<a href="/entry/313470">313470</a>) and MIC5 (<a href="/entry/308840">308840</a>) antigenic markers. The MIC5 gene was found to be between IDS and G6PD (<a href="/entry/305900">305900</a>). <a href="#23" class="mim-tip-reference" title="Couillin, P., Le Guern, E., Ravise, N., Grisard, M.-C., Oostra, B. A., Boue, A. &lt;strong&gt;Strategy for constructing somatic hybrids isolating the two derivative chromosomes in X;autosome translocations: application to a female patient t(X;5) with Hunter syndrome.&lt;/strong&gt; Ann. Genet. 33: 196-207, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2128908/&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;2128908&lt;/a&gt;]" pmid="2128908">Couillin et al. (1990)</a> concluded that the fragile X site is proximal to IDS. <a href="#98" class="mim-tip-reference" title="Wilson, P. J., Suthers, G. K., Callen, D. F., Baker, E., Nelson, P. V., Cooper, A., Wraith, J. E., Sutherland, G. R., Morris, C. P., Hopwood, J. J. &lt;strong&gt;Frequent deletions at Xq28 indicate genetic heterogeneity in Hunter syndrome.&lt;/strong&gt; Hum. Genet. 86: 505-508, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1901826/&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;1901826&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00194643&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="1901826">Wilson et al. (1991)</a> used an IDS cDNA clone to localize the gene to Xq28, distal to the fragile X site. The cDNA clone was also shown to span the X chromosome breakpoint in a female Hunter syndrome patient with an X;autosome translocation (<a href="#78" class="mim-tip-reference" title="Suthers, G. K., Callen, D. F., Hyland, V. J., Kozman, H. M., Baker, E., Eyre, H., Harper, P. S., Roberts, S. H., Hors-Cayla, M. C., Davies, K. E., Bell, M. V., Sutherland, G. R. &lt;strong&gt;A new DNA marker tightly linked to the fragile X locus (FRAXA).&lt;/strong&gt; Science 246: 1298-1300, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2573953/&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;2573953&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/science.2573953&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="2573953">Suthers et al., 1989</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1901826+2573953+2128908" 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>
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<a id="diagnosis" class="mim-anchor"></a>
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<strong>Diagnosis</strong>
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<p><a href="#83" class="mim-tip-reference" title="Tonnesen, T., Guttler, F., Lykkelund, C. &lt;strong&gt;Reliability of the use of fructose 1-phosphate to detect Hunter cells in fibroblast-cultures of obligate carriers of the Hunter syndrome.&lt;/strong&gt; Hum. Genet. 64: 371-375, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6225723/&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;6225723&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00292369&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="6225723">Tonnesen et al. (1983)</a> found that cross-correction between the 2 cell populations of the Hunter syndrome heterozygote is inhibited by fructose 1-phosphate or mannose 6-phosphate. Intercellular uptake of lysosomal enzymes in cultured fibroblasts is prevented by addition of either mannose-6-phosphate or fructose-1-phosphate to the culture medium. They studied 25 obligatory carriers to determine the usefulness of fructose 1-phosphate as a means of carrier detection. In 23 carriers, (35)S-sulfate incorporation was significantly increased. In 1 carrier, incorporation was already increased before addition of fructose and in 1 carrier it was normal both before and after fructose. <a href="#85" class="mim-tip-reference" title="Tonnesen, T. &lt;strong&gt;The use of fructose 1-phosphate to detect Hunter heterozygotes in fibroblast cultures from high-risk carriers.&lt;/strong&gt; Hum. Genet. 66: 212-216, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6425196/&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;6425196&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00286603&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="6425196">Tonnesen (1984)</a> identified Hunter carriers by studying (35)S-sulfate accumulation in the presence and absence of fructose-1-phosphate. <a href="#66" class="mim-tip-reference" title="Petruschka, L., Machill, G., Wehnert, M., Seidlitz, G., Knapp, A. &lt;strong&gt;Reliability of the Tonnesen technique for the identification of Hunter carriers.&lt;/strong&gt; Hum. Genet. 64: 404-406, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6413387/&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;6413387&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00292377&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="6413387">Petruschka et al. (1983)</a> tested the Tonnesen technique by studying various mixtures of normal and Hunter cells in culture as well as obligatory carriers. They concluded that the method 'seems to be suitable for carrier detection.' <a href="#1" class="mim-tip-reference" title="Archer, I. M., Young, I. D., Rees, D. W., Oladimeji, A., Wusteman, F. S., Harper, P. S. &lt;strong&gt;Carrier detection in Hunter syndrome.&lt;/strong&gt; Am. J. Med. Genet. 16: 61-69, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6227239/&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;6227239&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320160111&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="6227239">Archer et al. (1983)</a> concluded that carrier detection was best when hair-root analysis and serum enzyme levels were taken together. <a href="#26" class="mim-tip-reference" title="Daniele, A., Di Natale, P. &lt;strong&gt;Hunter syndrome: presence of material cross-reacting with antibodies against iduronate sulfatase.&lt;/strong&gt; Hum. Genet. 75: 234-238, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3104200/&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;3104200&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00281065&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="3104200">Daniele and Di Natale (1987)</a> demonstrated crossreacting material in the serum and fibroblasts of Hunter patients. <a href="#108" class="mim-tip-reference" title="Zlotogora, J., Bach, G. &lt;strong&gt;Hunter syndrome: prenatal diagnosis in maternal serum.&lt;/strong&gt; Am. J. Hum. Genet. 38: 253-260, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3080875/&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;3080875&lt;/a&gt;]" pmid="3080875">Zlotogora and Bach (1986)</a> proposed that prenatal diagnosis of Hunter syndrome may be possible by measurement of iduronate sulfatase in the mother's serum. The level of IDS consistently rises in the serum of pregnant women. In pregnancies with Hunter-affected male fetuses, serum enzyme levels did not change. The normal increase occurs usually by the sixth to twelfth week. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6227239+6425196+6225723+6413387+3080875+3104200" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Bakker, E., Kneppers, A., Deutz-Terlouw, P., Goor, J., Poorthuis, B., Kleyer, W., Niermeijer, M., Kamp, J., Hopwood, J., Ommen, G. &lt;strong&gt;Partial gene deletions in 3 out of 12 Dutch Hunter patients: direct and indirect carrier detection by DNA-analysis. (Abstract)&lt;/strong&gt; Cytogenet. Cell Genet. 58: 2055-2056, 1991."None>Bakker et al. (1991)</a> found that the IDS cDNA probe was partially deleted in 3 of 12 Dutch patients with Hunter syndrome. In 2 of the 3 patients, Southern blots showed the presence of a deletion junction fragment which could be used for highly reliable direct carrier detection in their families. <a href="#74" class="mim-tip-reference" title="Schroder, W., Petruschka, L., Wehnert, M., Zschiesche, M., Seidlitz, G., Hopwood, J. J., Herrmann, F. H. &lt;strong&gt;Carrier detection of Hunter syndrome (MPS II) by biochemical and DNA techniques in families at risk.&lt;/strong&gt; J. Med. Genet. 30: 210-213, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8097259/&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;8097259&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.30.3.210&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="8097259">Schroder et al. (1993)</a> used different carrier detection tests, i.e., IDS activity in serum, sulfate incorporation in cultured skin fibroblasts, and RFLP analysis, in 13 unrelated families with 16 patients and 36 females at risk for MPS II. Twenty-nine females were confirmed as carriers, and in 5 women, the heterozygous state was excluded. The use of the intragenic IDS cDNA probes and flanking probes provided accuracy in carrier detection that was equal to or better than biochemical methods. Structural alterations were found in the DNA of 2 patients: one showed a major deletion including the whole coding sequence of the IDS gene; an aberrant Southern fragment occurred in the HindIII/pc2S15 blot of the other patient, suggesting a new HindIII restriction site by point mutation in an IDS gene intron. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8097259" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Ben Simon-Schiff, E., Bach, G., Zlotogora, J., Abeliovich, D. &lt;strong&gt;Combined enzymatic and linkage analysis for heterozygote detection in Hunter syndrome: identification of an apparent case of germinal mosaicism.&lt;/strong&gt; Am. J. Med. Genet. 47: 837-842, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7904121/&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;7904121&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320470608&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="7904121">Ben Simon-Schiff et al. (1993)</a> confirmed the reliability of the serum assay of IDS activity in the identification of heterozygotes; the serum test correctly detected 11 of 12 of the first-degree relatives tested by the serum assay, 6 of 7 carriers, and 5 of 5 noncarriers. The only case with an apparent false negative result in the serum test was thought to represent an instance of germinal mosaicism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7904121" 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 family in which there was no surviving affected individual, <a href="#81" class="mim-tip-reference" title="Timms, K. M., Edwards, F. J., Belmont, J. W., Yates, J. R. W., Gibbs, R. A. &lt;strong&gt;Reassessment of biochemically determined Hunter syndrome carrier status by DNA testing.&lt;/strong&gt; J. Med. Genet. 35: 646-649, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9719370/&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;9719370&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.35.8.646&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="9719370">Timms et al. (1998)</a> described carrier testing using direct dye primer sequencing of PCR products to identify mixed bases in an obligate carrier. Two mixed bases were observed within exon 8 of the IDS gene. These resulted in a missense mutation and a nonsense mutation. Four additional female family members were screened for the same mutations, and none were found in any of these additional subjects, including in 1 who had been identified previously as a carrier by skin biopsy. <a href="#81" class="mim-tip-reference" title="Timms, K. M., Edwards, F. J., Belmont, J. W., Yates, J. R. W., Gibbs, R. A. &lt;strong&gt;Reassessment of biochemically determined Hunter syndrome carrier status by DNA testing.&lt;/strong&gt; J. Med. Genet. 35: 646-649, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9719370/&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;9719370&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.35.8.646&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="9719370">Timms et al. (1998)</a> concluded that this approach can be used to provide unambiguous information about a subject's carrier status, even in families in which the disorder is mild. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9719370" 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>As a means of molecular diagnosis, <a href="#42" class="mim-tip-reference" title="Jonsson, J. J., Aronovich, E. L., Braun, S. E., Whitley, C. B. &lt;strong&gt;Molecular diagnosis of mucopolysaccharidosis type II (Hunter syndrome) by automated sequencing and computer-assisted interpretation: toward mutation mapping of the iduronate-2-sulfatase gene.&lt;/strong&gt; Am. J. Hum. Genet. 56: 597-607, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7887413/&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;7887413&lt;/a&gt;]" pmid="7887413">Jonsson et al. (1995)</a> developed a rapid method to sequence the entire iduronate 2-sulfatase coding region: PCR amplicons representing the IDS cDNA were sequenced with an automatic machine, and output was analyzed by computer-assisted interpretation of tracings. Mutations were found in 10 of 11 patients studied. Unique missense mutations were identified in 5 patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7887413" 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>
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<a id="clinicalManagement" class="mim-anchor"></a>
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<strong>Clinical Management</strong>
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<p><a href="#12" class="mim-tip-reference" title="Braun, S. E., Aronovich, E. L., Anderson, R. A., Crotty, P. L., McIvor, R. S., Whitley, C. B. &lt;strong&gt;Metabolic correction and cross-correction of mucopolysaccharidosis type II (Hunter syndrome) by retroviral-mediated gene transfer and expression of human iduronate-2-sulfatase.&lt;/strong&gt; Proc. Nat. Acad. Sci. 90: 11830-11834, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8265633/&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;8265633&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.90.24.11830&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="8265633">Braun et al. (1993)</a> tested in vitro the correction of the enzyme defect in the Hunter syndrome, using an amphotropic retroviral vector containing the human IDS coding sequence. Lymphoblastoid cell lines from patients with Hunter syndrome were transduced with the vector and expressed high levels of IDS enzyme activity, 10- to 70-fold higher than normal human peripheral blood leukocytes or lymphoblastoid cell lines. The transduced cells failed to show accumulation of (35)SO4 into glycosaminoglycan, indicating that recombinant IDS enzyme participated in glycosaminoglycan metabolism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8265633" 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="#91" class="mim-tip-reference" title="Vellodi, A., Young, E., Cooper, A., Lidchi, V., Winchester, B., Wraith, J. E. &lt;strong&gt;Long-term follow-up following bone marrow transplantation for Hunter disease.&lt;/strong&gt; J. Inherit. Metab. Dis. 22: 638-648, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10399096/&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;10399096&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1005525931994&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="10399096">Vellodi et al. (1999)</a> reported the results of bone marrow transplantation performed in 10 patients with Hunter disease. The donor was an HLA-identical sib in 2 cases, an HLA-nonidentical relative in 6 cases, and a volunteer unrelated donor in 1 case. Details were not available in the last case. Only 3 patients had survived for more than 7 years post bone marrow transplant; of those, 1 died 11 years after bone marrow transplant. The authors suggested that this high mortality probably resulted from poor donor selection. In 2 who had survived long-term, there had been a steady progression of physical disability and mental handicap. One patient had maintained normal intellectual development, with only mild physical disability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10399096" 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="#93" class="mim-tip-reference" title="Wang, R. Y., Cambray-Forker, E. J., Ohanian, K., Karlin, D. S., Covault, K. K., Schwartz, P. H., Abdenur, J. E. &lt;strong&gt;Treatment reduces or stabilizes brain imaging abnormalities in patients with MPS I and II.&lt;/strong&gt; Molec. Genet. Metab. 98: 406-411, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19748810/&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;19748810&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2009.07.015&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="19748810">Wang et al. (2009)</a> reported 2 unrelated boys with MPS II diagnosed at ages 3 years 9 months and 4 years 7 months, respectively. One had moderate mental retardation and aggressive behavior, whereas the other was cognitively normal without behavioral problems. Both also had white matter abnormalities and ventricular dilatation on brain MRI, which did not correlate with cognitive function. Treatment with intravenous enzyme replacement therapy (ERT) resulted in no change in brain MRI findings in either patient, indicating lack of progression. The findings suggested that ERT may halt or possibly improve brain MRI abnormalities in patients with MPS, even though ERT had previously been thought not to cross into the brain. <a href="#93" class="mim-tip-reference" title="Wang, R. Y., Cambray-Forker, E. J., Ohanian, K., Karlin, D. S., Covault, K. K., Schwartz, P. H., Abdenur, J. E. &lt;strong&gt;Treatment reduces or stabilizes brain imaging abnormalities in patients with MPS I and II.&lt;/strong&gt; Molec. Genet. Metab. 98: 406-411, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19748810/&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;19748810&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2009.07.015&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="19748810">Wang et al. (2009)</a> offered some explanations, including lessening of somatic GAG accumulation, repair of damaged brain endothelium, and possibly small amounts of enzyme being able to permeate the brain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19748810" 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="#101" class="mim-tip-reference" title="Wraith, J. E., Scarpa, M., Beck, M., Bodamer, O. A., De Meirleir, L., Guffon, N., Lund, A. M., Malm, G., Van der Ploeg, A. T., Zeman, J. &lt;strong&gt;Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy.&lt;/strong&gt; Europ. J. Pediat. 167: 267-277, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18038146/&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;18038146&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=18038146[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/10.1007/s00431-007-0635-4&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="18038146">Wraith et al. (2008)</a> and <a href="#58" class="mim-tip-reference" title="Muenzer, J., Beck, M., Eng, C. M., Escolar, M. L., Giugliani, R., Guffon, N. H., Harmatz, P., Kamin, W., Kampmann, C., Koseoglu, S. T., Link, B., Martin, R. A., Molter, D. W., Munoz Rojas, M. V., Ogilvie, J. W., Parini, R., Ramaswami, U., Scarpa, M., Schwartz, I. V., Wood, R. E., Wraith, E. &lt;strong&gt;Multidisciplinary management of Hunter syndrome.&lt;/strong&gt; Pediatrics 124: e1228-e1239, 2009. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19901005/&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;19901005&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1542/peds.2008-0999&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="19901005">Muenzer et al. (2009)</a> reviewed the clinical management of patients with MPS II. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18038146+19901005" 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="#92" class="mim-tip-reference" title="Wang, R. Y., Bodamer, O. A., Watson, M. S., Wilcox, W. R. &lt;strong&gt;Lysosomal storage diseases: diagnostic confirmation and management of presymptomatic individuals.&lt;/strong&gt; Genet. Med. 13: 457-484, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21502868/&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;21502868&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/GIM.0b013e318211a7e1&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="21502868">Wang et al. (2011)</a> described the ACMG standards and guidelines for the diagnostic confirmation and management of presymptomatic individuals with lysosomal storage diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21502868" 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="#96" class="mim-tip-reference" title="Wikman-Jorgensen, P. E., Lopez Amoros, A., Peris Garcia, J., Esteve Atienzar, P. J., Canizares Navarro, R., Arsenio Tomas, M. L., Segui Ripoll, J. M., Bonet, D., Esteban-Giner, M. J., Robert, J., Giner-Galvan, V. &lt;strong&gt;Enzyme replacement therapy for the treatment of Hunter disease: a systematic review with narrative synthesis and meta-analysis.&lt;/strong&gt; Molec. Genet. Metab. 131: 206-210, 2020.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/32773276/&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;32773276&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2020.07.005&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="32773276">Wikman-Jorgensen et al. (2020)</a> performed a literature review to assess the safety and efficacy of ERT for the treatment of Hunter syndrome. The review included 42 articles, including 8 clinical trials, 21 observational studies, 12 clinical case reports, and 1 case-control study. All of the articles reported reduced urinary GAG content with ERT, and a dose response gradient was seen in the 3 studies in which different doses were evaluated. In 12 studies that evaluated the effect of ERT on distance walked on the 6 minute walk test, 8 reported an improvement in children and adults. Other findings with ERT included reduced liver and spleen size in 18 of 18 studies in which this outcome was reported, increased forced vital capacity on pulmonary function testing, reduction in the left ventricular mass index, and reduction in mortality. In all of the studies, improved quality of life with ERT was reported; however, a metaanalysis of the results was not possible due to the heterogeneous methodology across the studies. A clear effect of ERT was not observed on cognitive deterioration or growth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32773276" 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>
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<a id="populationGenetics" class="mim-anchor"></a>
<h4 href="#mimPopulationGeneticsFold" id="mimPopulationGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>Population Genetics</strong>
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<p><a href="#72" class="mim-tip-reference" title="Schaap, T., Bach, G. &lt;strong&gt;Incidence of mucopolysaccharidoses in Israel: is Hunter disease a &#x27;Jewish disease&#x27;?&lt;/strong&gt; Hum. Genet. 56: 221-223, 1980.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6821579/&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;6821579&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00295699&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="6821579">Schaap and Bach (1980)</a> reported a frequency of approximately 1 in 34,000 males born in Israel between 1967 and 1975. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6821579" 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 questionnaire study in the United Kingdom, <a href="#104" class="mim-tip-reference" title="Young, I. D., Harper, P. S. &lt;strong&gt;Incidence of Hunter&#x27;s syndrome. (Letter)&lt;/strong&gt; Hum. Genet. 60: 391-392, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6809596/&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;6809596&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00569230&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="6809596">Young and Harper (1982)</a> estimated the frequency of the Hunter syndrome as about 1 in 132,000 male births. The severe form was 3.38 times more frequent than the mild form. No increased incidence in Jews was noted. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6809596" 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 British Columbia, 6 cases of the Hunter syndrome were born between 1952 and 1986, giving a frequency of 1 in 110,950 live male births (<a href="#52" class="mim-tip-reference" title="Lowry, R. B., Applegarth, D. A., Toone, J. R., MacDonald, E., Thunem, N. Y. &lt;strong&gt;An update on the frequency of mucopolysaccharide syndromes in British Columbia.&lt;/strong&gt; Hum. Genet. 85: 389-390, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2118475/&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;2118475&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00206770&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="2118475">Lowry et al., 1990</a>). <a href="#17" class="mim-tip-reference" title="Chakravarti, A., Bale, S. J. &lt;strong&gt;Differences in the frequency of X-linked deleterious genes in human populations.&lt;/strong&gt; Am. J. Hum. Genet. 35: 1252-1257, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6418001/&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;6418001&lt;/a&gt;]" pmid="6418001">Chakravarti and Bale (1983)</a> concluded that the high frequency of Hunter disease in Israeli Jews (<a href="#35" class="mim-tip-reference" title="Goodman, R. M. &lt;strong&gt;Genetic Disorders among the Jewish People.&lt;/strong&gt; Baltimore: Johns Hopkins Univ. Press (pub.) 1979. Pp. 458-470."None>Goodman, 1979</a>) is compatible with genetic drift. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2118475+6418001" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using multiple ascertainment sources, <a href="#59" class="mim-tip-reference" title="Nelson, J., Crowhurst, J., Carey, B., Greed, L. &lt;strong&gt;Incidence of the mucopolysaccharidoses in western Australia.&lt;/strong&gt; Am. J. Med. Genet. 123A: 310-313, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14608657/&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;14608657&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.20314&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="14608657">Nelson et al. (2003)</a> estimated the incidence rate for mucopolysaccharidoses in western Australia for the period 1969 to 1996. An incidence of approximately 1 in 320,000 live births (1 in 165,000 male live births) was obtained for Hunter syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14608657" 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="#51" class="mim-tip-reference" title="Lin, H.-Y., Lin, S.-P., Chuang, C.-K., Niu, D.-M., Chen, M.-R., Tsai, F.-J., Chao, M.-C., Chiu, P.-C., Lin, S.-J., Tsai, L.-P., Hwu, W.-L., Lin, J.-L. &lt;strong&gt;Incidence of the mucopolysaccharidoses in Taiwan, 1984-2004.&lt;/strong&gt; Am. J. Med. Genet. 149A: 960-964, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19396827/&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;19396827&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.32781&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="19396827">Lin et al. (2009)</a> analyzed the incidence of MPS in Taiwan between 1984 and 2004 and found that the combined birth incidence for all MPS cases was 2.04 per 100,000 live births. MPS II (Hunter syndrome) had the highest calculated birth incidence (1.07 per 100,000 live births), comprising 52% of all MPS cases diagnosed. Although the overall incidence of MPS in Taiwan was consistent with reports from Western populations, <a href="#51" class="mim-tip-reference" title="Lin, H.-Y., Lin, S.-P., Chuang, C.-K., Niu, D.-M., Chen, M.-R., Tsai, F.-J., Chao, M.-C., Chiu, P.-C., Lin, S.-J., Tsai, L.-P., Hwu, W.-L., Lin, J.-L. &lt;strong&gt;Incidence of the mucopolysaccharidoses in Taiwan, 1984-2004.&lt;/strong&gt; Am. J. Med. Genet. 149A: 960-964, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19396827/&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;19396827&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.32781&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="19396827">Lin et al. (2009)</a> noted that in contrast to reports of a higher incidence of MPS I in most Western populations, their study showed a higher incidence of MPS II in Taiwan. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19396827" 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="Khan, S. A., Peracha, H., Ballhausen, D., Wiesbauer, A., Rohrbach, M., Gautschi, M., Mason, R. W., Giugliani, R., Suzuki, Y., Orii, K. E., Orii, T., Tomatsu, S. &lt;strong&gt;Epidemiology of mucopolysaccharidoses.&lt;/strong&gt; Molec. Genet. Metab. 121: 227-240, 2017.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/28595941/&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;28595941&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=28595941[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/10.1016/j.ymgme.2017.05.016&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="28595941">Khan et al. (2017)</a> analyzed the epidemiology of the mucopolysaccharidoses in Japan and Switzerland and compared them to similar data from other countries. Information for Japan was collected between 1982 and 2009, and 467 cases with MPS were identified. The combined birth prevalence was 1.53 per 100,000 live births. The highest birth prevalence was 0.84 for MPS II, accounting for 55% of all MPS. MPS I (see <a href="/entry/607014">607014</a>), III (see <a href="/entry/252900">252900</a>), and IV (see <a href="/entry/253000">253000</a>) accounted for 15%, 16%, and 10%, respectively. MPS VI (<a href="/entry/253200">253200</a>) and VII (<a href="/entry/253220">253220</a>) were more rare and accounted for 1.7% and 1.3%, respectively. A retrospective epidemiologic data collection was performed in Switzerland between 1975 and 2008 (34 years), and 41 living MPS patients were identified. The combined birth prevalence was 1.56 per 100,000 live births. The highest birth prevalence was 0.46 for MPS II, accounting for 29% of all MPS. MPS I, III, and IV accounted for 12%, 24%, and 24%, respectively. As seen in the Japanese population, MPS VI and VII were more rare and accounted for 7.3% and 2.4%, respectively. The high birth prevalence of MPS II in Japan was comparable to that seen in other East Asian countries where this MPS accounted for approximately 50% of all forms of MPS. Birth prevalence was also similar in some European countries (Germany, Northern Ireland, Portugal and the Netherlands) although the prevalence of other forms of MPS was also reported to be higher in these countries. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28595941" 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="#47" class="mim-tip-reference" title="Koto, Y., Sakai, N., Lee, Y., Kakee, N., Matsuda, J., Tsuboi, K., Shimozawa, N., Okuyama, T., Nakamura, K., Narita, A., kobayashi, H., Uehara, R., Nakamura, Y., Kato, K., Eto, Y. &lt;strong&gt;Prevalence of patients with lysosomal storage disorders and peroxisomal disorders: a nationwide survey in Japan.&lt;/strong&gt; Molec. Genet. Metab. 133: 277-288, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/34090759/&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;34090759&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2021.05.004&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="34090759">Koto et al. (2021)</a> surveyed hospitals in Japan for information about patients with lysosomal storage diseases (LSDs) treated between 2013-2016 and 2018-2019. MPS II was the second most common LSD after Fabry disease (<a href="/entry/301500">301500</a>), with 103 patients identified, of whom 31.1% had the severe form, 20.4% had the attenuated form, and 48.5% had an unknown form. When these data were extrapolated across Japan, <a href="#47" class="mim-tip-reference" title="Koto, Y., Sakai, N., Lee, Y., Kakee, N., Matsuda, J., Tsuboi, K., Shimozawa, N., Okuyama, T., Nakamura, K., Narita, A., kobayashi, H., Uehara, R., Nakamura, Y., Kato, K., Eto, Y. &lt;strong&gt;Prevalence of patients with lysosomal storage disorders and peroxisomal disorders: a nationwide survey in Japan.&lt;/strong&gt; Molec. Genet. Metab. 133: 277-288, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/34090759/&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;34090759&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2021.05.004&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="34090759">Koto et al. (2021)</a> estimated that there were 275 patients with MPS II. They calculated a birth prevalence in Japan of 0.38 per 100,000. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34090759" 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>
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<a id="molecularGenetics" class="mim-anchor"></a>
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>Molecular Genetics</strong>
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<p><a href="#98" class="mim-tip-reference" title="Wilson, P. J., Suthers, G. K., Callen, D. F., Baker, E., Nelson, P. V., Cooper, A., Wraith, J. E., Sutherland, G. R., Morris, C. P., Hopwood, J. J. &lt;strong&gt;Frequent deletions at Xq28 indicate genetic heterogeneity in Hunter syndrome.&lt;/strong&gt; Hum. Genet. 86: 505-508, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1901826/&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;1901826&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00194643&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="1901826">Wilson et al. (1991)</a> found a deletion or gene rearrangement in 7 of 23 Hunter patients of Australian and British origin. In 2 of 14 unrelated German MPS II patients, structural alteration of the IDS gene was found by Southern analysis using an IDS cDNA clone as a probe. In one of these patients, a severely affected male, no Southern fragments were detected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1901826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated patients with complete deletion of the IDS gene, <a href="#100" class="mim-tip-reference" title="Wraith, J. E., Cooper, A., Thornley, M., Wilson, P. J., Nelson, P. V., Morris, C. P., Hopwood, J. J. &lt;strong&gt;The clinical phenotype of two patients with a complete deletion of the iduronate-2-sulphatase gene (mucopolysaccharidosis II--Hunter syndrome).&lt;/strong&gt; Hum. Genet. 87: 205-206, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1906048/&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;1906048&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00204183&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="1906048">Wraith et al. (1991)</a> reported that the phenotype was that of very severe Hunter syndrome. In addition, both had features not commonly seen in MPS II, namely, early onset of seizures in one patient and ptosis in the other. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1906048" 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 12 patients, <a href="#15" class="mim-tip-reference" title="Bunge, S., Steglich, C., Beck, M., Rosenkranz, W., Schwinger, E., Hopwood, J. J., Gal, A. &lt;strong&gt;Mutation analysis of the iduronate-2-sulfatase gene in patients with mucopolysaccharidosis type II (Hunter syndrome).&lt;/strong&gt; Hum. Molec. Genet. 1: 335-339, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1303211/&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;1303211&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/1.5.335&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="1303211">Bunge et al. (1992)</a> used single-strand conformation polymorphism analysis for mutation analysis. Missense or nonsense mutations and deletions or insertions of a small number of basepairs were found in most; probably only about 20% of Hunter patients have complete deletion or gross structural alteration of the IDS gene. The broad clinical variability among Hunter patients is apparently a reflection of extensive molecular heterogeneity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1303211" 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="Palmieri, G., Capra, V., Romano, G., D&#x27;Urso, M., Johnson, S., Schlessinger, D., Morris, P., Hopwood, J., Di Natale, P., Gatti, R., Ballabio, A. &lt;strong&gt;The iduronate sulfatase gene: isolation of a 1.2-Mb YAC contig spanning the entire gene and identification of heterogeneous deletions in patients with Hunter syndrome.&lt;/strong&gt; Genomics 12: 52-57, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1733863/&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;1733863&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0888-7543(92)90405-h&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="1733863">Palmieri et al. (1992)</a> isolated a 1.2-Mb YAC contig spanning the IDS gene. Several putative CpG islands were identified in the region, suggesting the presence of other genes. Southern analysis of DNA from 25 unrelated Italian MPS II patients uncovered 4 with deletions or rearrangements in the IDS gene. DNA from a patient with a translocation breakpoint in the gene permitted orientation of the contig in relation to the centromere. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1733863" 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="#75" class="mim-tip-reference" title="Steen-Bondeson, M.-L., Dahl, N., Tonnesen, T., Kleijer, W. J., Seidlitz, G., Gustavson, K.-H., Wilson, P. J., Morris, C. P., Hopwood, J. J., Pettersson, U. &lt;strong&gt;Molecular analysis of patients with Hunter syndrome: implication of a region prone to structural alterations within the IDS gene.&lt;/strong&gt; Hum. Molec. Genet. 1: 195-198, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1303177/&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;1303177&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/1.3.195&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="1303177">Steen-Bondeson et al. (1992)</a> investigated the occurrence of rearrangements and deletions of the IDS gene in a Southern analysis of 46 unrelated MPS2 patients of different ethnic origins using a cDNA clone containing the entire IDS gene as a probe. Structural alterations were found in DNA from 9 patients, 2 of whom showed large deletions including all coding sequences of the gene. The distal and proximal breakpoints of these deletions were determined by hybridization of markers flanking the IDS gene. Seven of the observed alterations constituted major rearrangements of the gene. Six of these rearrangements showed similar or identical patterns by Southern analysis, suggestive of a region prone to structural alterations within the IDS gene. <a href="#75" class="mim-tip-reference" title="Steen-Bondeson, M.-L., Dahl, N., Tonnesen, T., Kleijer, W. J., Seidlitz, G., Gustavson, K.-H., Wilson, P. J., Morris, C. P., Hopwood, J. J., Pettersson, U. &lt;strong&gt;Molecular analysis of patients with Hunter syndrome: implication of a region prone to structural alterations within the IDS gene.&lt;/strong&gt; Hum. Molec. Genet. 1: 195-198, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1303177/&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;1303177&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/1.3.195&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="1303177">Steen-Bondeson et al. (1992)</a> also demonstrated the potential use of the IDS probe for carrier detection in families with a rearranged IDS gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1303177" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#29" class="mim-tip-reference" title="Froissart, R., Blond, J.-L., Maire, I., Guibaud, P., Hopwood, J. J., Mathieu, M., Bozon, D. &lt;strong&gt;Hunter syndrome: gene deletions and rearrangements.&lt;/strong&gt; Hum. Mutat. 2: 138-140, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8318991/&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;8318991&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.1380020214&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="8318991">Froissart et al. (1993)</a> described 2 patients who appeared to have complete deletion of the IDS gene. It appeared that these patients had a more severe form of Hunter syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8318991" 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 a study of a total of 26 cases, <a href="#16" class="mim-tip-reference" title="Bunge, S., Steglich, C., Zuther, C., Beck, M., Morris, C. P., Schwinger, E., Schinzel, A., Hopwood, J. J., Gal, A. &lt;strong&gt;Iduronate-2-sulfatase gene mutations in 16 patients with mucopolysaccharidosis type II (Hunter syndrome).&lt;/strong&gt; Hum. Molec. Genet. 2: 1871-1875, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8281149/&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;8281149&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/2.11.1871&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="8281149">Bunge et al. (1993)</a> found that about 20% of patients have deletions of the whole IDS gene or other major structural alterations. In about 23% of cases, deletion of 1, 2, or 3 basepairs was found, while the remaining patients, about 57%, carried point mutations predicting amino acid replacement, premature termination of translation, or aberrant splicing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8281149" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#38" class="mim-tip-reference" title="Hopwood, J. J., Bunge, S., Morris, C. P., Wilson, P. J., Steglich, C., Beck, M., Schwinger, E., Gal, A. &lt;strong&gt;Molecular basis of mucopolysaccharidosis type II: mutations in the iduronate-2-sulphatase gene.&lt;/strong&gt; Hum. Mutat. 2: 435-442, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8111411/&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;8111411&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.1380020603&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="8111411">Hopwood et al. (1993)</a> reviewed mutations in the IDS gene in Hunter syndrome. From the group of 319 patients thus far studied by Southern analysis, 14 had full deletion of the gene and 48 had partial deletion or other gross rearrangements. All patients with full deletions or gross rearrangements had severe clinical presentations. In a total of 32 patients, 29 different 'small' mutations had been characterized: 4 nonsense and 13 missense mutations, 7 different small deletions from 1 to 3 bp, with most leading to a frameshift and premature chain termination, and 5 different splice site mutations also leading to small insertions or deletions in the mRNA. A 60-bp deletion that resulted from the creation of a new donor splice site was observed in 5 unrelated patients with relatively mild clinical phenotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8111411" 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="#77" class="mim-tip-reference" title="Sukegawa, K., Tomatsu, S., Fukao, T., Iwata, H., Song, X.-Q., Yamada, Y., Fukuda, S., Isogai, K., Orii, T. &lt;strong&gt;Mucopolysaccharidosis type II (Hunter disease): identification and characterization of eight point mutations in the iduronate-2-sulfatase gene in Japanese patients.&lt;/strong&gt; Hum. Mutat. 6: 136-143, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7581397/&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;7581397&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.1380060206&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="7581397">Sukegawa et al. (1995)</a> described 8 new examples of point mutations in the IDS gene in Japanese Hunter syndrome patients exhibiting various degrees of severity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7581397" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Bondeson, M.-L., Dahl, N., Malmgren, H., Kleijer, W. J., Tonnesen, T., Carlberg, B.-M., Pettersson, U. &lt;strong&gt;Inversion of the IDS gene resulting from recombination with IDS-related sequences is a common cause of the Hunter syndrome.&lt;/strong&gt; Hum. Molec. Genet. 4: 615-621, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7633410/&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;7633410&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/4.4.615&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="7633410">Bondeson et al. (1995)</a> identified an IDS pseudogene, which they designated IDS2, located within 90 kb telomeric of the IDS gene. They showed that this region is involved in a recombination event with the primary IDS gene in about 13% of patients with the Hunter syndrome. Analysis of the resulting rearrangement at the molecular level showed that these patients had suffered a recombination event that resulted in a disruption of the IDS gene in intron 7 with an inversion of the intervening DNA. All 6 patients with a similar type of rearrangement showed recombination between intron 7 of the IDS gene and sequences close to exon 3 of the IDS2 locus, implying that these regions are hotspots for recombination. Nucleotide sequencing showed that the inversion is caused by recombination between homologous sequences present in the IDS gene and the IDS2 locus. No detectable deletions or insertions were observed as a consequence of the recombination. The IDS2 pseudogene contains sequences that are related to exons 2 and 3 as well as introns 2, 3, and 7 of the IDS gene. An example of a similar inversion caused by homologous recombination is that involving intron 22 of the factor VIII gene (F8; <a href="/entry/300841">300841</a>) causing severe hemophilia A (<a href="/entry/306700">306700</a>). In the case of the F8 gene, the inversions occur almost exclusively in the male germ cells. It has therefore been hypothesized that mispairing leading to inversion is inhibited by pairing of the X chromosomes in the female germ cells. Interestingly, both the F8 gene and the IDS gene are located in Xq28, a distal part of the X chromosome that is generally unpaired in males. <a href="#10" class="mim-tip-reference" title="Bondeson, M.-L., Malmgren, H., Dahl, N., Carlberg, B.-M., Pettersson, U. &lt;strong&gt;Presence of an IDS-related locus (IDS2) in Xq28 complicates the mutational analysis of Hunter syndrome.&lt;/strong&gt; Europ. J. Hum. Genet. 3: 219-227, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8528670/&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;8528670&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1159/000472302&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="8528670">Bondeson et al. (1995)</a> provided additional information concerning the IDS2 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8528670+7633410" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Birot, A.-M., Bouton, O., Froissart, R., Maire, I., Bozon, D. &lt;strong&gt;IDS gene-pseudogene exchange responsible for an intragenic deletion in a Hunter patient.&lt;/strong&gt; Hum. Mutat. 8: 44-50, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8807335/&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;8807335&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1098-1004(1996)8:1&lt;44::AID-HUMU6&gt;3.0.CO;2-P&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="8807335">Birot et al. (1996)</a> described a patient with Hunter syndrome in whom an exchange between the IDS gene and pseudogene through interchromosomal recombination had apparently caused internal deletion of exons 4, 5, 6, and 7. In the rearranged gene, the junction intron contained pseudogene intron 3- and intron 7-related sequences. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8807335" 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="#67" class="mim-tip-reference" title="Rathmann, M., Bunge, S., Beck, M., Kresse, H., Tylki-Szymanska, A., Gal, A. &lt;strong&gt;Mucopolysaccharidosis type II (Hunter syndrome): mutation &#x27;hot spots&#x27; in the iduronate-2-sulfatase gene.&lt;/strong&gt; Am. J. Hum. Genet. 59: 1202-1209, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8940265/&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;8940265&lt;/a&gt;]" pmid="8940265">Rathmann et al. (1996)</a> identified IDS mutations in 31 families/patients with MPS II. Twenty mutations were novel and unique and another was novel but was found in 3 unrelated patients. One of the mutations detected was of special interest as it is an A-to-G substitution in an intron far from the coding region that is deleterious because it creates a new 5-prime splice donor site that results in the inclusion of a 78-bp intronic sequence (<a href="/entry/300823#0014">300823.0014</a>). The authors analyzed a total of 101 point mutations in the coding region and found that they tended to be more frequent in exons 3, 8, and 9. CpG dinucleotides were involved in 47% of the point mutations, of which G:C-to-A:T transitions constituted nearly 80%. Almost all recurrent point mutations involved CpG sites. Analysis of a collection of 50 families studied by this group revealed that mutations occurred more frequently in male meioses; they estimated the male-to-female ratio to be between 3.76 and 6.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8940265" 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="#31" class="mim-tip-reference" title="Froissart, R., Maire, I., Millat, G., Cudry, S., Birot, A.-M., Bonnet, V., Bouton, O., Bozon, D. &lt;strong&gt;Identification of iduronate sulfatase gene alterations in 70 unrelated Hunter patients.&lt;/strong&gt; Clin. Genet. 53: 362-368, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9660053/&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;9660053&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1998.tb02746.x&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="9660053">Froissart et al. (1998)</a> studied 70 unrelated Hunter patients and found a mutation in each. There was striking molecular heterogeneity. Large gene rearrangements were identified in 14 patients. In the 56 other patients, 43 different mutations were identified, and 31 had not previously been described. Since only a few mutations were present in several patients, genotype/phenotype correlations were difficult. The mother was not found to be a carrier in 5 among 44 sporadic cases. Haplotype analysis demonstrated a high frequency of mutations in male meiosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9660053" 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="#41" class="mim-tip-reference" title="Isogai, K., Sukegawa, K., Tomatsu, S., Fukao, T., Song, X.-Q., Yamada, Y., Fukuda, S., Orii, T., Kondo, N. &lt;strong&gt;Mutation analysis in the iduronate-2-sulphatase gene in 43 Japanese patients with mucopolysaccharidosis type II (Hunter disease).&lt;/strong&gt; J. Inherit. Metab. Dis. 21: 60-70, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9501270/&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;9501270&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1005363414792&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="9501270">Isogai et al. (1998)</a> characterized 25 different small mutations in the IDS gene in a series of 43 Japanese patients with Hunter disease. As in other series, 3 different mutations in codon 468 of exon 9 were found: arg468 to trp (<a href="#0012">309900.0012</a>), arg468 to gln (<a href="#0013">309900.0013</a>), arg468 to leu (<a href="#0015">309900.0015</a>). All 3 mutations were associated with a severe phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9501270" 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="#82" class="mim-tip-reference" title="Timms, K. M., Huckett, L. E., Belmont, J. W., Shapira, S. K., Gibbs, R. A. &lt;strong&gt;DNA deletion confined to the iduronate-2-sulfatase promoter abolishes IDS gene expression.&lt;/strong&gt; Hum. Mutat. 11: 121-126, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9482575/&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;9482575&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1098-1004(1998)11:2&lt;121::AID-HUMU4&gt;3.0.CO;2-M&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="9482575">Timms et al. (1998)</a> described a patient with features of moderate to severe Hunter syndrome and a 178-bp deletion upstream of IDS exon 1 spanning a predicted promoter element. Sequencing of all 9 IDS exons failed to show any additional mutations within the coding region or in intron/exon boundaries. The 178-bp deletion was flanked by 2 13-bp direct repeats and potential DNA topoisomerase II recognition sites. These findings suggested to <a href="#82" class="mim-tip-reference" title="Timms, K. M., Huckett, L. E., Belmont, J. W., Shapira, S. K., Gibbs, R. A. &lt;strong&gt;DNA deletion confined to the iduronate-2-sulfatase promoter abolishes IDS gene expression.&lt;/strong&gt; Hum. Mutat. 11: 121-126, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9482575/&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;9482575&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1098-1004(1998)11:2&lt;121::AID-HUMU4&gt;3.0.CO;2-M&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="9482575">Timms et al. (1998)</a> nonhomologous recombination as a possible mechanism for the deletion. Expression studies detected no IDS transcripts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9482575" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study of 31 Spanish families with Hunter disease, <a href="#36" class="mim-tip-reference" title="Gort, L., Chabas, A., Coll, M. J. &lt;strong&gt;Hunter disease in the Spanish population: molecular analysis in 31 families.&lt;/strong&gt; J. Inherit. Metab. Dis. 21: 655-661, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9762601/&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;9762601&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1005432600871&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="9762601">Gort et al. (1998)</a> found 22 novel small mutations (7 reported previously by the same group) and 4 large deletions or rearrangements. This brought the number of separate IDS mutations that had been reported to that time to nearly 150. <a href="#50" class="mim-tip-reference" title="Li, P., Bellows, A. B., Thompson, J. N. &lt;strong&gt;Molecular basis of iduronate-2-sulphatase gene mutations in patients with mucopolysaccharidosis type II (Hunter syndrome).&lt;/strong&gt; J. Med. Genet. 36: 21-27, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9950361/&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;9950361&lt;/a&gt;]" pmid="9950361">Li et al. (1999)</a> provided yet more evidence of the molecular heterogeneity of this condition by identifying 17 mutations in 18 unrelated patients with MPS2. The mutations included 7 missense mutations, 5 small deletions, 2 insertions, 2 splice site mutations, and an intragenic deletion of exons 4, 5, 6, and 7. Nine of the small mutations were novel. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9950361+9762601" 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 36 Russian patients with Hunter syndrome, <a href="#44" class="mim-tip-reference" title="Karsten, S., Voskoboeva, E., Tishkanina, S., Pettersson, U., Krasnopolskaja, X., Bondeson, M.-L. &lt;strong&gt;Mutational spectrum of the iduronate-2-sulfatase (IDS) gene in 36 unrelated Russian MPS II patients.&lt;/strong&gt; Hum. Genet. 103: 732-735, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9921913/&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;9921913&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s004390050901&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="9921913">Karsten et al. (1998)</a> found 25 different mutations, of which 15 were novel. Most of the missense mutations resulted in intermediate or severe phenotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9921913" 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>
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<a id="genotypePhenotypeCorrelations" class="mim-anchor"></a>
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<p>In a review, <a href="#58" class="mim-tip-reference" title="Muenzer, J., Beck, M., Eng, C. M., Escolar, M. L., Giugliani, R., Guffon, N. H., Harmatz, P., Kamin, W., Kampmann, C., Koseoglu, S. T., Link, B., Martin, R. A., Molter, D. W., Munoz Rojas, M. V., Ogilvie, J. W., Parini, R., Ramaswami, U., Scarpa, M., Schwartz, I. V., Wood, R. E., Wraith, E. &lt;strong&gt;Multidisciplinary management of Hunter syndrome.&lt;/strong&gt; Pediatrics 124: e1228-e1239, 2009. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19901005/&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;19901005&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1542/peds.2008-0999&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="19901005">Muenzer et al. (2009)</a> noted that a paucity of common and recurrent mutations in the IDS gene makes genotype/phenotype correlations difficult. They stated that complete deletions and complex rearrangements of the IDS gene always result in a severe phenotype. Although 3 mutations in codon 468 of exon 9 (<a href="/entry/300823#0012">300823.0012</a>, <a href="/entry/300823#0013">300823.0013</a>, <a href="/entry/300823#0015">300823.0015</a>) have been associated with a severe phenotype, each has also been reported in patients with attenuated phenotypes. Similarly, the 1122C-T transition (<a href="/entry/300823#0002">300823.0002</a>), which creates an alternate splice site with the loss of 20 amino acids, is primarily associated with an attenuated phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19901005" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Contiguous Gene Deletion on Xq28 Involving the IDS Gene</em></strong></p><p>
In a patient with classic severe Hunter syndrome who also suffered from epileptic seizures, <a href="#75" class="mim-tip-reference" title="Steen-Bondeson, M.-L., Dahl, N., Tonnesen, T., Kleijer, W. J., Seidlitz, G., Gustavson, K.-H., Wilson, P. J., Morris, C. P., Hopwood, J. J., Pettersson, U. &lt;strong&gt;Molecular analysis of patients with Hunter syndrome: implication of a region prone to structural alterations within the IDS gene.&lt;/strong&gt; Hum. Molec. Genet. 1: 195-198, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1303177/&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;1303177&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/1.3.195&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="1303177">Steen-Bondeson et al. (1992)</a> identified a deletion with a proximal breakpoint between DXS295 and DXS296. They noted that epileptic seizures were also described in 2 patients reported by <a href="#98" class="mim-tip-reference" title="Wilson, P. J., Suthers, G. K., Callen, D. F., Baker, E., Nelson, P. V., Cooper, A., Wraith, J. E., Sutherland, G. R., Morris, C. P., Hopwood, J. J. &lt;strong&gt;Frequent deletions at Xq28 indicate genetic heterogeneity in Hunter syndrome.&lt;/strong&gt; Hum. Genet. 86: 505-508, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1901826/&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;1901826&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00194643&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="1901826">Wilson et al. (1991)</a> and <a href="#100" class="mim-tip-reference" title="Wraith, J. E., Cooper, A., Thornley, M., Wilson, P. J., Nelson, P. V., Morris, C. P., Hopwood, J. J. &lt;strong&gt;The clinical phenotype of two patients with a complete deletion of the iduronate-2-sulphatase gene (mucopolysaccharidosis II--Hunter syndrome).&lt;/strong&gt; Hum. Genet. 87: 205-206, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1906048/&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;1906048&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00204183&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="1906048">Wraith et al. (1991)</a> with a complete deletion of the IDS gene. A comparison of the breakpoints in the 3 patients suggested that a gene or genes located in the vicinity to the IDS gene may be involved in the development of epilepsy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1303177+1906048+1901826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Birot, A. M., Delobel, B., Gronnier, P., Bonnet, V., Maire, I., Bozon, D. &lt;strong&gt;A 5-megabase familial deletion removes the IDS and FMR-1 genes in a male Hunter patient.&lt;/strong&gt; Hum. Mutat. 7: 266-268, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8829661/&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;8829661&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1098-1004(1996)7:3&lt;266::AID-HUMU12&gt;3.0.CO;2-0&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="8829661">Birot et al. (1996)</a> described a family with a cytogenetically evident deletion in Xq27.2-q28 that removed the IDS and FMR1 genes. This was said to be the largest deletion in this region of the X chromosome identified in a male patient, indicating that absence of any of the genes in this region would not be lethal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8829661" 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="#80" class="mim-tip-reference" title="Timms, K. M., Bondeson, M.-L., Ansari-Lari, M. A., Lagerstedt, K., Muzny, D. M., Dugan-Rocha, S. P., Nelson, D. L., Pettersson, U., Gibbs, R. A. &lt;strong&gt;Molecular and phenotypic variation in patients with severe Hunter syndrome.&lt;/strong&gt; Hum. Molec. Genet. 6: 479-486, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9147653/&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;9147653&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/6.3.479&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="9147653">Timms et al. (1997)</a> used genomic DNA sequencing to identify several new genes in the IDS region. DNA deletion patients with atypical symptoms were analyzed to determine whether these atypical symptoms could be due to involvement of these other loci. The occurrence of seizures in 2 individuals correlated with a deletion extending proximal to IDS, up to and including part of the FMR2 locus (<a href="/entry/309548">309548</a>). Other (nonseizure) symptoms were associated with distal deletions. In addition, a group of patients with no variant symptoms, and a characteristic rearrangement involving a recombination between the IDS gene and an adjacent IDS pseudogene, showed normal expression of loci distal to IDS. <a href="#80" class="mim-tip-reference" title="Timms, K. M., Bondeson, M.-L., Ansari-Lari, M. A., Lagerstedt, K., Muzny, D. M., Dugan-Rocha, S. P., Nelson, D. L., Pettersson, U., Gibbs, R. A. &lt;strong&gt;Molecular and phenotypic variation in patients with severe Hunter syndrome.&lt;/strong&gt; Hum. Molec. Genet. 6: 479-486, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9147653/&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;9147653&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/6.3.479&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="9147653">Timms et al. (1997)</a> concluded that together these results identified FMR2 as a candidate gene for seizures, when mutated along with IDS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9147653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#43" class="mim-tip-reference" title="Karsten, S. L., Lagerstedt, K., Carlberg, B.-M., Kleijer, W. J., Zaremba, J., Van Diggelen, O. P., Czartoryska, B., Pettersson, U., Bondeson, M.-L. &lt;strong&gt;Two distinct deletions in the IDS gene and the gene W: a novel type of mutation associated with the Hunter syndrome.&lt;/strong&gt; Genomics 43: 123-129, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9244428/&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;9244428&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1006/geno.1997.4811&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="9244428">Karsten et al. (1997)</a> noted that the region of the IDS gene, in addition to the IDS2 gene that harbors sequences homologous to exons 2 and 3 and introns 2, 3, and 7, contains several novel genes (e.g., genes W, X, and Y). In addition, a neighboring region has undergone a duplication and exists in an inverted version on the telomeric side of IDS. <a href="#43" class="mim-tip-reference" title="Karsten, S. L., Lagerstedt, K., Carlberg, B.-M., Kleijer, W. J., Zaremba, J., Van Diggelen, O. P., Czartoryska, B., Pettersson, U., Bondeson, M.-L. &lt;strong&gt;Two distinct deletions in the IDS gene and the gene W: a novel type of mutation associated with the Hunter syndrome.&lt;/strong&gt; Genomics 43: 123-129, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9244428/&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;9244428&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1006/geno.1997.4811&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="9244428">Karsten et al. (1997)</a> identified 2 distinct deletions separated by 30 kb in a patient with Hunter syndrome. One deletion included exons 5 and 6 of the IDS gene; the second deletion included exons 3 and 4 of the W gene, located telomeric of the IDS gene. Both deletions were the result of nonhomologous (illegitimate) recombination events between short direct repeats at the deletion breakpoints. <a href="#48" class="mim-tip-reference" title="Lagerstedt, K., Carlberg, B.-M., Karimi-Nejad, R., Kleijer, W. J., Bondeson, M.-L. &lt;strong&gt;Analysis of a 43.6 kb deletion in a patient with Hunter syndrome (MPSII): identification of a fusion transcript including sequences from the gene W and the IDS gene.&lt;/strong&gt; Hum. Mutat. 15: 324-331, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10737977/&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;10737977&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1098-1004(200004)15:4&lt;324::AID-HUMU4&gt;3.0.CO;2-5&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="10737977">Lagerstedt et al. (2000)</a> analyzed a 43.6-kb deletion in a patient with Hunter syndrome and found a fusion transcript including sequences from the gene W and the IDS gene. Surprisingly, a similar but longer fusion transcript containing exons 2-4 of gene W and exons 4-9 of the IDS gene could be detected in RNA of normal cell lines originating from various tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10737977+9244428" 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>
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<p><a href="#97" class="mim-tip-reference" title="Wilkerson, M. J., Lewis, D. C., Marks, S. L., Prieur, D. J. &lt;strong&gt;Clinical and morphologic features of mucopolysaccharidosis type II in a dog: naturally occurring model of Hunter syndrome.&lt;/strong&gt; Vet. Path. 35: 230-233, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9598589/&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;9598589&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1177/030098589803500311&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="9598589">Wilkerson et al. (1998)</a> described Hunter syndrome in a Labrador retriever. The findings included coarse facial features, macrodactyly, unilateral corneal dystrophy (an atypical feature for type II mucopolysaccharidosis), generalized osteopenia, progressive neurologic deterioration, and a positive urine spot test for acid mucopolysaccharides. Deficiency in iduronate-2-sulfatase was demonstrated in cultured dermal fibroblasts. Hair root analysis for IDS showed that the dam (mother) was a carrier and that a phenotypically normal male littermate was normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9598589" 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="#32" class="mim-tip-reference" title="Garcia, A. R., Pan, J., Lamsa, J. C., Muenzer, J. &lt;strong&gt;The characterization of a murine model of mucopolysaccharidosis II (Hunter syndrome).&lt;/strong&gt; J. Inherit. Metab. Dis. 30: 924-934, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17876721/&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;17876721&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10545-007-0641-8&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="17876721">Garcia et al. (2007)</a> observed that male Ids-null mice showed increased urinary GAG excretion from 4 weeks of age through their life span. Tissue GAG levels were increased by 7 weeks of age. The mutant mice also showed hepatomegaly, splenomegaly, and enlargement of other organs compared to wildtype mice. Other features included coarse fur and sporadic alopecia, joint limitation, curved digits, abnormal skull development, decreased activity, and significantly decreased life span. Radiographic studies showed sclerosis and enlargement of the skull and appendicular bones. There was periosteal bone formation in the distal tibiae and calcification of the calcaneus tendon. Histologic studies revealed diffuse presence of foamy, vacuolated cell types in multiple organs. <a href="#32" class="mim-tip-reference" title="Garcia, A. R., Pan, J., Lamsa, J. C., Muenzer, J. &lt;strong&gt;The characterization of a murine model of mucopolysaccharidosis II (Hunter syndrome).&lt;/strong&gt; J. Inherit. Metab. Dis. 30: 924-934, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17876721/&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;17876721&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10545-007-0641-8&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="17876721">Garcia et al. (2007)</a> noted the similarities to human disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17876721" 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>
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<strong>History</strong>
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<p><a href="#60" class="mim-tip-reference" title="Neufeld, E. F., Liebaers, I., Epstein, C. J., Yatsiv, S., Milunsky, A., Migeon, B. R. &lt;strong&gt;The Hunter syndrome in females: is there an autosomal recessive form of iduronate sulfatase deficiency?&lt;/strong&gt; Am. J. Hum. Genet. 29: 455-461, 1977.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/409284/&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;409284&lt;/a&gt;]" pmid="409284">Neufeld et al. (1977)</a> described 2 families, each with a girl clinically affected with the Hunter syndrome and with profound deficiency of iduronate 2-sulfatase. The patients were karyotypically normal and had normal fathers. Cloning of the mothers' fibroblasts did not show the mosaicism expected of the X-linked disease. Homozygosity for a previously unsuspected autosomal recessive gene for iduronate sulfatase was considered the most likely explanation, although heterozygosity for the X-linked gene and subsequent selection could not be completely excluded. Studies of the enzyme at the molecular level and of complementation in somatic cell hybrids are required to distinguish between these possibilities. The mutation in the 2 families was presumably different (although perhaps allelic) because it took the severe form in one family and the mild form in the other. Strong support for autosomal recessive inheritance came from the fact that the parents were first cousins in one family and had ancestors from the same ethnic group and same small town in the other family. <a href="#61" class="mim-tip-reference" title="Neufeld, E. F. &lt;strong&gt;Personal Communication.&lt;/strong&gt; Bethesda, Md. 3/8/1981."None>Neufeld (1981)</a> suggested that these cases may have been instances of multiple sulfatase deficiency (<a href="/entry/272200">272200</a>) in which the deficiency of iduronate sulfatase is particularly striking. In 1 of the families, however, this did not appear to be the explanation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=409284" 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>
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<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>See Also:</strong>
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<a href="#Bach1973" class="mim-tip-reference" title="Bach, G., Eisenberg, F., Jr., Cantz, M., Neufeld, E. F. &lt;strong&gt;The defect in the Hunter syndrome: deficiency of sulfoiduronate sulfatase.&lt;/strong&gt; Proc. Nat. Acad. Sci. 70: 2134-2138, 1973.">Bach et al. (1973)</a>; <a href="#Booth1974" class="mim-tip-reference" title="Booth, C. W., Nadler, H. L. &lt;strong&gt;Demonstration of the heterozygous state in Hunter&#x27;s syndrome.&lt;/strong&gt; Pediatrics 53: 396-399, 1974.">Booth and Nadler (1974)</a>; <a href="#Brown1982" class="mim-tip-reference" title="Brown, F. R., III, Hall, C. W., Neufeld, E. F., Munoz, L. L., Braine, H., Andrzejewski, S., Camargo, E. E., Mark, S. A., Richard, J. M., Moser, H. W. &lt;strong&gt;Administration of iduronate sulfatase by plasma exchange to patients with the Hunter syndrome: a clinical study.&lt;/strong&gt; Am. J. Med. Genet. 13: 309-318, 1982.">Brown et al. (1982)</a>; <a href="#Clarke1990" class="mim-tip-reference" title="Clarke, J. T. R., Willard, H. F., Teshima, I., Chang, P. L., Skomorowski, M. A. &lt;strong&gt;Hunter disease (mucopolysaccharidosis type II) in a karyotypically normal girl.&lt;/strong&gt; Clin. Genet. 37: 355-362, 1990.">Clarke et al. (1990)</a>; <a href="#Danes1967" class="mim-tip-reference" title="Danes, B. S., Bearn, A. G. &lt;strong&gt;Hurler&#x27;s syndrome: a genetic study of clones in cell culture with particular reference to the Lyon hypothesis.&lt;/strong&gt; J. Exp. Med. 126: 509-522, 1967.">Danes and Bearn (1967)</a>; <a href="#Dean1979" class="mim-tip-reference" title="Dean, M. F., Stevens, R. L., Muir, H., Benson, P. F., Button, L. A., Anderson, R. L., Boylston, A., Mowbray, J. &lt;strong&gt;Enzyme replacement therapy by fibroblast transplantation: long term biochemical study in three cases of Hunter&#x27;s syndrome.&lt;/strong&gt; J. Clin. Invest. 63: 138-145, 1979.">Dean et al. (1979)</a>; <a href="#Gerich1969" class="mim-tip-reference" title="Gerich, J. E. &lt;strong&gt;Hunter&#x27;s syndrome: beta-galactosidase deficiency in skin.&lt;/strong&gt; New Eng. J. Med. 280: 799-802, 1969.">Gerich (1969)</a>; <a href="#Hunter1917" class="mim-tip-reference" title="Hunter, C. &lt;strong&gt;A rare disease in two brothers.&lt;/strong&gt; Proc. R. Soc. Med. 10: 104-106, 1917.">Hunter (1917)</a>; <a href="#Kleijer1979" class="mim-tip-reference" title="Kleijer, W. J., Mooy, P. D., Liebaers, I., van de Kamp, J. J. P., Niermeijer, M. F. &lt;strong&gt;Prenatal monitoring for the Hunter syndrome: the heterozygous female fetus.&lt;/strong&gt; Clin. Genet. 15: 113-117, 1979.">Kleijer et al. (1979)</a>; <a href="#Migeon1977" class="mim-tip-reference" title="Migeon, B. R., Sprenkle, J. A., Liebaers, I., Scott, J. F., Neufeld, E. F. &lt;strong&gt;X-linked Hunter syndrome: the heterozygous phenotype in cell culture.&lt;/strong&gt; Am. J. Hum. Genet. 29: 448-454, 1977.">Migeon et al.
(1977)</a>; <a href="#Nwokoro1979" class="mim-tip-reference" title="Nwokoro, N., Neufeld, E. F. &lt;strong&gt;Detection of Hunter heterozygotes by enzymatic analysis of hair roots.&lt;/strong&gt; Am. J. Hum. Genet. 31: 42-49, 1979.">Nwokoro and Neufeld (1979)</a>; <a href="#Ockerman1968" class="mim-tip-reference" title="Ockerman, P. A., Kohlin, P. &lt;strong&gt;Glycosidases in skin and plasma in Hunter&#x27;s syndrome: abnormality of a beta-galactosidase in skin.&lt;/strong&gt; Acta Paediat. Scand. 57: 281-284, 1968.">Ockerman and Kohlin (1968)</a>; <a href="#Schachern1984" class="mim-tip-reference" title="Schachern, P. A., Shea, D. A., Paparella, M. M. &lt;strong&gt;Mucopolysaccharidosis I-H (Hurler&#x27;s syndrome) and human temporal bone histopathology.&lt;/strong&gt; Ann. Otol. Rhinol. Laryng. 93: 65-69, 1984.">Schachern et al. (1984)</a>; <a href="#Tonnesen1982" class="mim-tip-reference" title="Tonnesen, T., Lykkelund, C., Guttler, F. &lt;strong&gt;Diagnosis of Hunter&#x27;s syndrome carriers; radioactive sulphate incorporation into fibroblasts in the presence of fructose 1-phosphate.&lt;/strong&gt; Hum. Genet. 60: 167-171, 1982.">Tonnesen et al. (1982)</a>; <a href="#Upadhyaya1985" class="mim-tip-reference" title="Upadhyaya, M., Bamforth, S., Young, I., Thomas, N., Sarfarazi, M., Davies, K., Harper, P. S. &lt;strong&gt;Hunter&#x27;s syndrome: evidence supporting a location on the distal part of the X chromosome long arm. (Abstract)&lt;/strong&gt; J. Med. Genet. 22: 394-395, 1985.">Upadhyaya et al.
(1985)</a>; <a href="#Van1960" class="mim-tip-reference" title="Van Pelt, J. F. &lt;strong&gt;Gargoylism.&lt;/strong&gt; Thesis: Nijmegen (pub.) 1960.">Van Pelt (1960)</a>; <a href="#Wehnert1992" class="mim-tip-reference" title="Wehnert, M., Hopwood, J. J., Schroder, W., Herrmann, F. H. &lt;strong&gt;Structural gene aberrations in mucopolysaccharidosis II (Hunter).&lt;/strong&gt; Hum. Genet. 89: 430-432, 1992.">Wehnert et al. (1992)</a>; <a href="#Wiesmann1980" class="mim-tip-reference" title="Wiesmann, U. N., Spycher, M. A., Meier, C., Liebaers, I., Herschkowitz, N. &lt;strong&gt;Prenatal mucopolysaccharidosis II (Hunter): a pathogenetic study.&lt;/strong&gt; Pediat. Res. 14: 749-756, 1980.">Wiesmann et al.
(1980)</a>; <a href="#Yatziv1977" class="mim-tip-reference" title="Yatziv, S., Erickson, R. P., Epstein, C. J. &lt;strong&gt;Mild and severe Hunter syndrome (MPS II) within the same sibships.&lt;/strong&gt; Clin. Genet. 11: 319-326, 1977.">Yatziv et al. (1977)</a>; <a href="#Young1979" class="mim-tip-reference" title="Young, I. D., Harper, P. S. &lt;strong&gt;Long-term complications in Hunter&#x27;s syndrome.&lt;/strong&gt; Clin. Genet. 16: 125-132, 1979.">Young and Harper (1979)</a>; <a href="#Yutaka1978" class="mim-tip-reference" title="Yutaka, T., Fluharty, A. L., Stevens, R. L., Kihara, H. &lt;strong&gt;Iduronate sulfatase analysis of hair roots for identification of Hunter syndrome heterozygotes.&lt;/strong&gt; Am. J. Hum. Genet. 30: 575-582, 1978.">Yutaka et al.
(1978)</a>; <a href="#Zlotogora1984" class="mim-tip-reference" title="Zlotogora, J., Bach, G. &lt;strong&gt;Heterozygote detection in Hunter syndrome.&lt;/strong&gt; Am. J. Med. Genet. 17: 661-665, 1984.">Zlotogora and Bach (1984)</a>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
<a id="Archer1983" class="mim-anchor"></a>
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Archer, I. M., Young, I. D., Rees, D. W., Oladimeji, A., Wusteman, F. S., Harper, P. S.
<strong>Carrier detection in Hunter syndrome.</strong>
Am. J. Med. Genet. 16: 61-69, 1983.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6227239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6227239</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6227239" 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.1320160111" target="_blank">Full Text</a>]
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<a id="Bach1973" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bach, G., Eisenberg, F., Jr., Cantz, M., Neufeld, E. F.
<strong>The defect in the Hunter syndrome: deficiency of sulfoiduronate sulfatase.</strong>
Proc. Nat. Acad. Sci. 70: 2134-2138, 1973.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4269173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4269173</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4269173" 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.70.7.2134" target="_blank">Full Text</a>]
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<a id="Bakker1991" class="mim-anchor"></a>
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Bakker, E., Kneppers, A., Deutz-Terlouw, P., Goor, J., Poorthuis, B., Kleyer, W., Niermeijer, M., Kamp, J., Hopwood, J., Ommen, G.
<strong>Partial gene deletions in 3 out of 12 Dutch Hunter patients: direct and indirect carrier detection by DNA-analysis. (Abstract)</strong>
Cytogenet. Cell Genet. 58: 2055-2056, 1991.
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<a id="Ballenger1980" class="mim-anchor"></a>
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Ballenger, C. E., Swift, T. R., Leshner, R. T., El Gammal, T. A., McDonald, T. F.
<strong>Myelopathy in mucopolysaccharidosis type II (Hunter syndrome).</strong>
Ann. Neurol. 7: 382-385, 1980.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6769383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6769383</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6769383" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ana.410070418" target="_blank">Full Text</a>]
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<a id="Ben Simon-Schiff1993" class="mim-anchor"></a>
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Ben Simon-Schiff, E., Bach, G., Zlotogora, J., Abeliovich, D.
<strong>Combined enzymatic and linkage analysis for heterozygote detection in Hunter syndrome: identification of an apparent case of germinal mosaicism.</strong>
Am. J. Med. Genet. 47: 837-842, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7904121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7904121</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7904121" 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.1320470608" target="_blank">Full Text</a>]
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<a id="Berg1968" class="mim-anchor"></a>
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Berg, K., Danes, B. S., Bearn, A. G.
<strong>The linkage relation of the loci for the Xm serum system and the X-linked form of Hurler's syndrome (Hunter's syndrome).</strong>
Am. J. Hum. Genet. 20: 398-401, 1968.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4969416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4969416</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4969416" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Birot1996" class="mim-anchor"></a>
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Birot, A. M., Delobel, B., Gronnier, P., Bonnet, V., Maire, I., Bozon, D.
<strong>A 5-megabase familial deletion removes the IDS and FMR-1 genes in a male Hunter patient.</strong>
Hum. Mutat. 7: 266-268, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8829661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8829661</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8829661" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/(SICI)1098-1004(1996)7:3&lt;266::AID-HUMU12&gt;3.0.CO;2-0" target="_blank">Full Text</a>]
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<a id="Birot1996" class="mim-anchor"></a>
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Birot, A.-M., Bouton, O., Froissart, R., Maire, I., Bozon, D.
<strong>IDS gene-pseudogene exchange responsible for an intragenic deletion in a Hunter patient.</strong>
Hum. Mutat. 8: 44-50, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8807335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8807335</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8807335" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/(SICI)1098-1004(1996)8:1&lt;44::AID-HUMU6&gt;3.0.CO;2-P" target="_blank">Full Text</a>]
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<a id="Bondeson1995" class="mim-anchor"></a>
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Bondeson, M.-L., Dahl, N., Malmgren, H., Kleijer, W. J., Tonnesen, T., Carlberg, B.-M., Pettersson, U.
<strong>Inversion of the IDS gene resulting from recombination with IDS-related sequences is a common cause of the Hunter syndrome.</strong>
Hum. Molec. Genet. 4: 615-621, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7633410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7633410</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7633410" 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/4.4.615" target="_blank">Full Text</a>]
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<li>
<a id="10" class="mim-anchor"></a>
<a id="Bondeson1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bondeson, M.-L., Malmgren, H., Dahl, N., Carlberg, B.-M., Pettersson, U.
<strong>Presence of an IDS-related locus (IDS2) in Xq28 complicates the mutational analysis of Hunter syndrome.</strong>
Europ. J. Hum. Genet. 3: 219-227, 1995.
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[<a href="https://doi.org/10.1159/000472302" target="_blank">Full Text</a>]
</p>
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<a id="11" class="mim-anchor"></a>
<a id="Booth1974" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Booth, C. W., Nadler, H. L.
<strong>Demonstration of the heterozygous state in Hunter's syndrome.</strong>
Pediatrics 53: 396-399, 1974.
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</p>
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<li>
<a id="12" class="mim-anchor"></a>
<a id="Braun1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Braun, S. E., Aronovich, E. L., Anderson, R. A., Crotty, P. L., McIvor, R. S., Whitley, C. B.
<strong>Metabolic correction and cross-correction of mucopolysaccharidosis type II (Hunter syndrome) by retroviral-mediated gene transfer and expression of human iduronate-2-sulfatase.</strong>
Proc. Nat. Acad. Sci. 90: 11830-11834, 1993.
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[<a href="https://doi.org/10.1073/pnas.90.24.11830" target="_blank">Full Text</a>]
</p>
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<a id="13" class="mim-anchor"></a>
<a id="Broadhead1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Broadhead, D. M., Kirk, J. M., Burt, A. J., Gupta, V., Ellis, P. M., Besley, G. T. N.
<strong>Full expression of Hunter's disease in a female with an X-chromosome deletion leading to non-random inactivation.</strong>
Clin. Genet. 30: 392-398, 1986.
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[<a href="https://doi.org/10.1111/j.1399-0004.1986.tb01896.x" target="_blank">Full Text</a>]
</p>
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<a id="14" class="mim-anchor"></a>
<a id="Brown1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Brown, F. R., III, Hall, C. W., Neufeld, E. F., Munoz, L. L., Braine, H., Andrzejewski, S., Camargo, E. E., Mark, S. A., Richard, J. M., Moser, H. W.
<strong>Administration of iduronate sulfatase by plasma exchange to patients with the Hunter syndrome: a clinical study.</strong>
Am. J. Med. Genet. 13: 309-318, 1982.
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[<a href="https://doi.org/10.1002/ajmg.1320130314" target="_blank">Full Text</a>]
</p>
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<a id="Bunge1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bunge, S., Steglich, C., Beck, M., Rosenkranz, W., Schwinger, E., Hopwood, J. J., Gal, A.
<strong>Mutation analysis of the iduronate-2-sulfatase gene in patients with mucopolysaccharidosis type II (Hunter syndrome).</strong>
Hum. Molec. Genet. 1: 335-339, 1992.
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[<a href="https://doi.org/10.1093/hmg/1.5.335" target="_blank">Full Text</a>]
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<a id="16" class="mim-anchor"></a>
<a id="Bunge1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bunge, S., Steglich, C., Zuther, C., Beck, M., Morris, C. P., Schwinger, E., Schinzel, A., Hopwood, J. J., Gal, A.
<strong>Iduronate-2-sulfatase gene mutations in 16 patients with mucopolysaccharidosis type II (Hunter syndrome).</strong>
Hum. Molec. Genet. 2: 1871-1875, 1993.
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[<a href="https://doi.org/10.1093/hmg/2.11.1871" target="_blank">Full Text</a>]
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<a id="Chakravarti1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Chakravarti, A., Bale, S. J.
<strong>Differences in the frequency of X-linked deleterious genes in human populations.</strong>
Am. J. Hum. Genet. 35: 1252-1257, 1983.
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<a id="Chase1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Chase, D. S., Morris, A. H., Ballabio, A., Pepper, S., Giannelli, F., Adinolfi, M.
<strong>Genetics of Hunter syndrome: carrier detection, new mutations, segregation and linkage analysis.</strong>
Ann. Hum. Genet. 50: 349-360, 1986.
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[<a href="https://doi.org/10.1111/j.1469-1809.1986.tb01756.x" target="_blank">Full Text</a>]
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<a id="Clarke1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Clarke, J. T. R., Greer, W. L., Strasberg, P. M., Pearce, R. D., Skomorowski, M. A., Ray, P. N.
<strong>Hunter disease (mucopolysaccharidosis type II) associated with unbalanced inactivation of the X chromosomes in a karyotypically normal girl.</strong>
Am. J. Hum. Genet. 49: 289-297, 1991.
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<a id="Clarke1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Clarke, J. T. R., Pearce, R. D., Greer, W. L., Strasberg, P., Ray, P. N.
<strong>Hunter disease (MPS, type II) in a karyotypically normal girl associated with selective X-chromosome inactivation. (Abstract)</strong>
Am. J. Hum. Genet. 47 (suppl.): A52 only, 1990.
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<div class="">
<p class="mim-text-font">
Clarke, J. T. R., Willard, H. F., Teshima, I., Chang, P. L., Skomorowski, M. A.
<strong>Hunter disease (mucopolysaccharidosis type II) in a karyotypically normal girl.</strong>
Clin. Genet. 37: 355-362, 1990.
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[<a href="https://doi.org/10.1111/j.1399-0004.1990.tb03519.x" target="_blank">Full Text</a>]
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<a id="Clarke1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Clarke, J. T. R., Wilson, P. J., Morris, C. P., Hopwood, J. J., Richards, R. I., Sutherland, G. R., Ray, P. N.
<strong>Characterization of a deletion at Xq27-q28 associated with unbalanced inactivation of the nonmutant X chromosome.</strong>
Am. J. Hum. Genet. 51: 316-322, 1992.
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<a id="Couillin1990" class="mim-anchor"></a>
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<p class="mim-text-font">
Couillin, P., Le Guern, E., Ravise, N., Grisard, M.-C., Oostra, B. A., Boue, A.
<strong>Strategy for constructing somatic hybrids isolating the two derivative chromosomes in X;autosome translocations: application to a female patient t(X;5) with Hunter syndrome.</strong>
Ann. Genet. 33: 196-207, 1990.
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</p>
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<a id="Danes1965" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Danes, B. S., Bearn, A. G.
<strong>Hurler's syndrome: demonstration of an inherited disorder of connective tissue in cell culture.</strong>
Science 149: 987-989, 1965.
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[<a href="https://doi.org/10.1126/science.149.3687.987" target="_blank">Full Text</a>]
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<a id="Danes1967" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Danes, B. S., Bearn, A. G.
<strong>Hurler's syndrome: a genetic study of clones in cell culture with particular reference to the Lyon hypothesis.</strong>
J. Exp. Med. 126: 509-522, 1967.
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[<a href="https://doi.org/10.1084/jem.126.3.509" target="_blank">Full Text</a>]
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<a id="Daniele1987" class="mim-anchor"></a>
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<p class="mim-text-font">
Daniele, A., Di Natale, P.
<strong>Hunter syndrome: presence of material cross-reacting with antibodies against iduronate sulfatase.</strong>
Hum. Genet. 75: 234-238, 1987.
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[<a href="https://doi.org/10.1007/BF00281065" target="_blank">Full Text</a>]
</p>
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<a id="Dean1979" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Dean, M. F., Stevens, R. L., Muir, H., Benson, P. F., Button, L. A., Anderson, R. L., Boylston, A., Mowbray, J.
<strong>Enzyme replacement therapy by fibroblast transplantation: long term biochemical study in three cases of Hunter's syndrome.</strong>
J. Clin. Invest. 63: 138-145, 1979.
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[<a href="https://doi.org/10.1172/JCI109267" target="_blank">Full Text</a>]
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<a id="DiFerrante1972" class="mim-anchor"></a>
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DiFerrante, N. M., Nichols, B. L., Jr.
<strong>A case of the Hunter syndrome with progeny.</strong>
Johns Hopkins Med. J. 130: 325-328, 1972.
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<a id="Froissart1993" class="mim-anchor"></a>
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Froissart, R., Blond, J.-L., Maire, I., Guibaud, P., Hopwood, J. J., Mathieu, M., Bozon, D.
<strong>Hunter syndrome: gene deletions and rearrangements.</strong>
Hum. Mutat. 2: 138-140, 1993.
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[<a href="https://doi.org/10.1002/humu.1380020214" target="_blank">Full Text</a>]
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<a id="Froissart1997" class="mim-anchor"></a>
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Froissart, R., Maire, I., Bonnet, V., Levade, T., Bozon, D.
<strong>Germline and somatic mosaicism in a female carrier of Hunter disease.</strong>
J. Med. Genet. 34: 137-140, 1997.
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[<a href="https://doi.org/10.1136/jmg.34.2.137" target="_blank">Full Text</a>]
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<div class="">
<p class="mim-text-font">
Froissart, R., Maire, I., Millat, G., Cudry, S., Birot, A.-M., Bonnet, V., Bouton, O., Bozon, D.
<strong>Identification of iduronate sulfatase gene alterations in 70 unrelated Hunter patients.</strong>
Clin. Genet. 53: 362-368, 1998.
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[<a href="https://doi.org/10.1111/j.1399-0004.1998.tb02746.x" target="_blank">Full Text</a>]
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Garcia, A. R., Pan, J., Lamsa, J. C., Muenzer, J.
<strong>The characterization of a murine model of mucopolysaccharidosis II (Hunter syndrome).</strong>
J. Inherit. Metab. Dis. 30: 924-934, 2007.
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[<a href="https://doi.org/10.1007/s10545-007-0641-8" target="_blank">Full Text</a>]
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<a id="Gerich1969" class="mim-anchor"></a>
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Gerich, J. E.
<strong>Hunter's syndrome: beta-galactosidase deficiency in skin.</strong>
New Eng. J. Med. 280: 799-802, 1969.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4975290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4975290</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4975290" 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/NEJM196904102801502" target="_blank">Full Text</a>]
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<a id="Goldenfum1996" class="mim-anchor"></a>
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[<a href="https://doi.org/10.1002/(SICI)1098-1004(1996)7:1&lt;76::AID-HUMU14&gt;3.0.CO;2-P" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1023/a:1005432600871" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.ophtha.2015.01.015" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1023/a:1005363414792" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1006/geno.1997.4811" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s004390050901" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2017.05.016" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.1979.tb01749.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2021.05.004" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/(SICI)1098-1004(200004)15:4&lt;324::AID-HUMU4&gt;3.0.CO;2-5" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0888-7543(90)90169-u" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1542/peds.2008-0999" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00292377" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.26.5.309" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0190-9622(98)70280-4" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00295699" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00292369" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00569706" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00286603" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1651-2227.1987.tb10577.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00280492" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1023/a:1005525931994" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1097/GIM.0b013e318211a7e1" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2009.07.015" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00194316" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1203/00006450-198005000-00008" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1177/030098589803500311" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00194643" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.1320440625" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00204183" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s00431-007-0635-4" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.1977.tb01323.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.1979.tb00861.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00569230" target="_blank">Full Text</a>]
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<strong>Heterozygote detection in Hunter syndrome.</strong>
Am. J. Med. Genet. 17: 661-665, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6424473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6424473</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6424473" 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.1320170317" target="_blank">Full Text</a>]
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<a id="Zlotogora1986" class="mim-anchor"></a>
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Zlotogora, J., Bach, G.
<strong>Hunter syndrome: prenatal diagnosis in maternal serum.</strong>
Am. J. Hum. Genet. 38: 253-260, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3080875/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3080875</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3080875" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
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<a id="109" class="mim-anchor"></a>
<a id="Zlotogora1985" class="mim-anchor"></a>
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Zlotogora, J., Schaap, T., Zeigler, M., Bach, G.
<strong>Hunter syndrome among Ashkenazi Jews in Israel; evidence for prenatal selection favoring the Hunter allele.</strong>
Hum. Genet. 71: 329-332, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3935563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3935563</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3935563" 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/BF00388459" target="_blank">Full Text</a>]
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<a id="Zlotogora1991" class="mim-anchor"></a>
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Zlotogora, J., Schaap, T., Zeigler, M., Bach, G.
<strong>Hunter syndrome in Jews in Israel: further evidence for prenatal selection favoring the Hunter allele.</strong>
Hum. Genet. 86: 531-533, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1901828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1901828</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1901828" 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/BF00194650" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 09/13/2021
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Hilary J. Vernon - updated : 04/06/2021<br>Ada Hamosh - updated : 05/29/2018<br>Jane Kelly - updated : 4/18/2016<br>Ada Hamosh - updated : 2/25/2015<br>Ada Hamosh - updated : 10/4/2012<br>Cassandra L. Kniffin - updated : 8/16/2010<br>Marla J. F. O'Neill - updated : 10/30/2009<br>Cassandra L. Kniffin - updated : 2/29/2008<br>Victor A. McKusick - updated : 6/15/2004<br>Victor A. McKusick - updated : 1/5/2004<br>Gary A. Bellus - updated : 9/4/2003<br>Victor A. McKusick - updated : 6/23/2003<br>Victor A. McKusick - updated : 1/14/2002<br>Victor A. McKusick - updated : 4/19/2000<br>Ada Hamosh - updated : 7/15/1999<br>Victor A. McKusick - updated : 6/17/1999<br>Michael J. Wright - updated : 2/12/1999<br>Victor A. McKusick - updated : 1/21/1999<br>Michael J. Wright - updated : 11/16/1998<br>Victor A. McKusick - updated : 10/13/1998<br>Victor A. McKusick - updated : 9/15/1998<br>Ada Hamosh - updated : 8/13/1998<br>Victor A. McKusick - updated : 6/12/1998<br>Victor A. McKusick - updated : 3/26/1998<br>Victor A. McKusick - updated : 11/26/1997<br>Victor A. McKusick - updated : 8/26/1997<br>Victor A. McKusick - updated : 4/15/1997<br>Victor A. McKusick - updated : 3/6/1997<br>Victor A. McKusick - updated : 2/18/1997<br>Victor A. McKusick - updated : 2/7/1997
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Creation Date:
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Victor A. McKusick : 6/4/1986
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carol : 01/13/2023
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carol : 02/22/2022<br>carol : 09/13/2021<br>carol : 04/07/2021<br>carol : 04/06/2021<br>carol : 07/12/2019<br>carol : 05/31/2018<br>carol : 05/30/2018<br>alopez : 05/29/2018<br>alopez : 05/29/2018<br>alopez : 05/29/2018<br>carol : 10/17/2016<br>carol : 04/19/2016<br>carol : 4/18/2016<br>alopez : 2/25/2015<br>alopez : 2/25/2015<br>carol : 2/12/2014<br>mcolton : 2/12/2014<br>mcolton : 2/12/2014<br>alopez : 10/4/2012<br>carol : 4/7/2011<br>carol : 9/1/2010<br>wwang : 8/18/2010<br>ckniffin : 8/16/2010<br>wwang : 11/6/2009<br>terry : 10/30/2009<br>wwang : 5/27/2009<br>carol : 10/31/2008<br>wwang : 3/19/2008<br>wwang : 3/4/2008<br>ckniffin : 2/29/2008<br>ckniffin : 10/19/2007<br>terry : 8/3/2005<br>tkritzer : 6/23/2004<br>terry : 6/15/2004<br>alopez : 3/17/2004<br>carol : 1/14/2004<br>cwells : 1/5/2004<br>carol : 10/17/2003<br>alopez : 9/4/2003<br>cwells : 6/27/2003<br>terry : 6/23/2003<br>mgross : 4/8/2002<br>carol : 3/13/2002<br>carol : 1/17/2002<br>carol : 1/17/2002<br>mcapotos : 1/14/2002<br>mcapotos : 1/14/2002<br>terry : 4/19/2000<br>alopez : 7/23/1999<br>terry : 7/15/1999<br>jlewis : 6/23/1999<br>terry : 6/17/1999<br>carol : 5/24/1999<br>alopez : 5/11/1999<br>carol : 3/22/1999<br>mgross : 3/1/1999<br>terry : 2/12/1999<br>carol : 2/1/1999<br>terry : 1/21/1999<br>alopez : 12/8/1998<br>terry : 11/16/1998<br>carol : 10/19/1998<br>terry : 10/13/1998<br>carol : 10/5/1998<br>carol : 9/18/1998<br>terry : 9/15/1998<br>carol : 8/13/1998<br>carol : 6/15/1998<br>terry : 6/15/1998<br>terry : 6/12/1998<br>alopez : 5/21/1998<br>alopez : 3/26/1998<br>terry : 3/20/1998<br>alopez : 12/5/1997<br>alopez : 12/3/1997<br>alopez : 12/3/1997<br>dholmes : 12/1/1997<br>mark : 9/11/1997<br>jenny : 9/5/1997<br>terry : 8/26/1997<br>alopez : 7/29/1997<br>alopez : 7/8/1997<br>jenny : 4/15/1997<br>terry : 4/9/1997<br>mark : 3/6/1997<br>terry : 3/4/1997<br>jenny : 2/18/1997<br>terry : 2/12/1997<br>terry : 2/7/1997<br>terry : 2/3/1997<br>terry : 1/17/1997<br>terry : 1/16/1997<br>jamie : 1/15/1997<br>terry : 1/7/1997<br>terry : 8/22/1996<br>mark : 7/22/1996<br>terry : 7/2/1996<br>terry : 6/27/1996<br>mark : 1/31/1996<br>terry : 1/25/1996<br>mark : 1/23/1996<br>mark : 1/22/1996<br>mark : 10/2/1995<br>pfoster : 7/6/1995<br>davew : 8/22/1994<br>warfield : 4/20/1994<br>mimadm : 4/18/1994<br>carol : 3/12/1994
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<strong>#</strong> 309900
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MUCOPOLYSACCHARIDOSIS, TYPE II; MPS2
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<em>Alternative titles; symbols</em>
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MPS II<br />
HUNTER SYNDROME<br />
IDURONATE 2-SULFATASE DEFICIENCY<br />
IDS DEFICIENCY<br />
SULFOIDURONATE SULFATASE DEFICIENCY<br />
SIDS DEFICIENCY
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<strong>SNOMEDCT:</strong> 70737009; &nbsp;
<strong>ICD10CM:</strong> E76.1; &nbsp;
<strong>ORPHA:</strong> 217085, 217093, 580; &nbsp;
<strong>DO:</strong> 12799; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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Xq28
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Mucopolysaccharidosis II
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309900
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X-linked recessive
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3
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IDS
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300823
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because mucopolysaccharidosis type II (MPS2), also known as Hunter syndrome, is caused by mutation in the gene encoding iduronate 2-sulfatase (IDS; 300823) on chromosome Xq28.</p>
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<strong>Description</strong>
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<p>Mucopolysaccharidosis II (MPS2) is a rare X-linked recessive disorder caused by deficiency of the lysosomal enzyme iduronate sulfatase, leading to progressive accumulation of glycosaminoglycans in nearly all cell types, tissues, and organs. Patients with MPS II excrete excessive amounts of chondroitin sulfate B (dermatan sulfate) and heparitin sulfate (heparan sulfate) in the urine (McKusick, 1972; Wraith et al., 2008). </p>
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<strong>Clinical Features</strong>
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<p>MPS II is a multisystem disorder. Clinical manifestations include severe airway obstruction, skeletal deformities, cardiomyopathy, and, in most patients, neurologic decline. Death usually occurs in the second decade of life, although some patients with less severe disease have survived into their fifth or sixth decade (summary by Wraith et al., 2008). </p><p>McKusick (1972) recognized 2 clinically distinguishable forms of MPS II: a severe form (called MPS IIA) with progressive mental retardation and physical disability and death before age 15 years in most cases, and a mild form (called MPS IIB; see later) compatible with survival to adulthood in which reproduction is known to have occurred (DiFerrante and Nichols, 1972) and in which intellect is impaired minimally, if at all. McKusick (1972) noted a lack of corneal clouding in the X-linked form of MPS as opposed to the autosomal forms (see MPS I-H, 607014). </p><p>Wraith et al. (2008) stated that MPS II should be regarded as a continuum between 2 extremes (severe and attenuated). They noted that although the clinical course for the more severely affected patients is relatively predictable, there is considerable variability in the clinical phenotype and progression of the more attenuated form of the disease. </p><p>Danes and Bearn (1965) found that fibroblasts from patients with this disorder show metachromatic cytoplasmic inclusions and that about half the fibroblasts of heterozygotes show such inclusions. </p><p>Sapadin and Friedman (1998) noted extensive Mongolian spots in a 4.5-year-old African American boy with Hunter syndrome. These patches were present at birth over the buttocks and lumbar sacral area. Other patches continued to appear over the paraspinal area of the entire back, and smaller lesions occurred on the anterior trunk. 'Pebbly' skin first appeared on the proximal arms, soon after became visible on the scapulas and thighs, and later in the pectoral areas. The other features were typical of Hunter syndrome, which was confirmed by enzyme assay. </p><p>Ochiai et al. (2003) investigated the occurrence of Mongolian spots in 7 Japanese infants with Hunter syndrome before and after hematopoietic stem cell transplantation (HSCT). Pre-HSCT observation revealed that all the patients had extensive Mongolian spots that were present at birth and showed no signs of resolution during the post-HSCT period. Electron microscopic findings showed that pigment-bearing dermal melanocytes contained many free melanosomes in stage IV. These were surrounded by extracellular sheaths and encircled by elastic fibers. The results of Ochiai et al. (2003) indicated a strong clinical correlation between extensive Mongolian spots and Hunter syndrome, and ultrastructural findings suggested that the hyperpigmentation is a long-lasting symptom. Ochiai et al. (2003) concluded that recognition of extensive Mongolian spots is essential as it may lead to early diagnosis in patients with mild forms of Hunter syndrome. </p><p>Huang et al. (2015) described chorioretinopathy in 5 patients with Hunter syndrome. In 2 patients (aged 9 and 20 years) with multifocal depigmented retinopathy, spectral-domain optical coherence tomography (SD-OCT) showed focal choroidal thinning in the pigmentary retinopathy areas. A mild, fuzzy, and thickened external limiting membrane (ELM), widening of the distance between the retinal pigment epithelium and ellipsoid zone at the fovea, and disruption of the ellipsoid zone at the extrafoveal area were also noted. In an 18-year-old man with a history of retinoschisis, SD-OCT showed mild retinal folds, a fuzzy and thickened ELM at the fovea, and some small cystic changes. In 2 patients (aged 10 and 14 years) with retinopathy resembling retinitis pigmentosa, SD-OCT showed some cystic spaces, a fuzzy ELM, disrupted ellipsoid zone, and diffuse loss of choriocapillaris. </p><p><strong><em>Attenuated Mucopolysaccharidosis Type II (MPS IIB)</em></strong></p><p>
Hobolth and Pedersen (1978) described a kindred with 6 cases of mild Hunter syndrome additionally remarkable for survival to ages 65 and 87 in 2 of the cases and for progeny from 3 affected males.</p><p>Tsuzaki et al. (1987) described an unusually mild form of Hunter syndrome. At 14 years of age, their patient had normal growth and development. He had mild dysostosis radiologically, coarse facial features, flexion contractures of the elbows and shoulder joints, and moderate hepatosplenomegaly. At age 8 he had the murmur of aortic regurgitation, and at age 12 angiocardiography was said to have shown grade 4 aortic regurgitation. The mother was a healthy carrier. Ballenger et al. (1980) described spastic quadriplegia in a 24-year-old man due to impingement of the thickened meninges on the cervical spinal cord. Tracheal narrowing required tracheostomy. </p><p>Yund et al. (2015) studied the association of brain volumes and somatic disease burden with neuropsychologic outcomes, including measures of intelligence, memory, and attention in 20 patients with attenuated MPS II with a mean age of 15.8 years. MRI volumes were compared to 55 normal controls. IQ and memory were average, but measures of attention were 1 SD below the average range. Corpus callosum volumes were significantly different from age-matched controls, differing by 22%. Normal age-related volume increases in white matter were not seen in MPS II patients as they were in controls. Somatic disease burden and white matter and corpus callosum volumes were significantly associated with attention deficits. Neither age at evaluation nor age at starting treatment predicted attention outcomes. </p><p><strong><em>Clinical Variability</em></strong></p><p>
Patients with complete deletion of the IDS locus often have atypical phenotypes, including ptosis, obstructive sleep apnea, and seizures (Wraith et al., 1991; Froissart et al., 1993). Steen-Bondeson et al. (1992) and others have suggested that some of these atypical features in Hunter syndrome patients may be caused by deletion of additional genes in the region of IDS; see MOLECULAR GENETICS section. </p>
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<strong>Inheritance</strong>
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<p>Hunter syndrome is an X-linked recessive disorder (McKusick, 1972). The disorder is expected to be found only in males, but some females have been reported.</p><p>Broadhead et al. (1986) described a 2.5-year-old girl with typical full expression of MPS II. Chromosome studies showed partial deletion of the long arm of one X chromosome; band Xq25 was thought to be missing. Studies using BrdU indicated that the deleted X chromosome was consistently late replicating and, as a result, the Hunter gene presumed to be present on the other X chromosome was fully expressed. There were no other cases of Hunter syndrome known in the family; however, the mother had a partial deficiency (43%) of serum iduronate-2-sulfate sulfatase. The father's serum enzyme activity was in the control range. Hence, caution must obviously be exercised in interpreting the findings of X/autosome translocations as indication of an X-linked trait at the site of the breakpoint on the X chromosome, when there is no way to identify carrier status in the mother. In such instances, the full expression of the disorder in a female may merely be the result of nonrandom inactivation of the abnormal X chromosome uncovering the mutant gene on the other X chromosome. </p><p>Clarke et al. (1990) described clinically and biochemically typical Hunter syndrome in a karyotypically normal girl. Cross-correction with fibroblasts of a classic male patient did not occur. In a second report, Clarke et al. (1990) presented evidence they interpreted as indicating that in this patient the maternal X chromosome was selectively inactivated, whereas presumably the paternal X chromosome carried a mutation for this disorder. The critical evidence was provided by somatic cell hybrid clones produced by fusion of the patient's fibroblasts with HPRT-negative hamster fibroblasts and grown in HAT-ouabain medium to select for hybrids containing at least one active human X chromosome. Clarke et al. (1991) presented further evidence in support of this hypothesis. </p><p>Clarke et al. (1992) reported molecular characterization of the mutation associated with marked unbalanced expression of the mutant X chromosome in the karyotypically normal girl with Hunter syndrome reported by Clarke et al. (1990, 1991). Southern analysis of DNA extracted from somatic cell hybrids containing only the mutant X chromosome showed deletion of several Xq27.3-q28 loci including FRAXA (309550) and the 3-prime end of the IDS gene. Three flanking loci, including DXS52, were intact. On the basis of these results, Clarke et al. (1992) concluded that the mutation was a simple deletion extending a maximum of 3-5 cM to the centromeric side of the IDS gene. Their studies indicated that the telomeric terminus of the deletion was located near the middle of the coding sequence of the gene. </p><p>Winchester et al. (1992) reported the occurrence of Hunter syndrome in a karyotypically normal girl who was 1 of identical twins. Molecular studies showed nonrandom X inactivation in both her fibroblasts and her lymphocytes, while her normal twin showed equal usage of the 2 X chromosomes. In view of previous reports of 7 pairs of identical female twins in which 1 had Duchenne muscular dystrophy, Winchester et al. (1992) suggested that twinning may be strongly associated with nonrandom X inactivation. In some cases of twins discordant for DMD, symmetric nonrandom X inactivation was found with each twin showing a nonrandom pattern but in opposite directions. In at least one case (Lupski et al., 1991), however, 1 girl showed an apparently random pattern and the affected girl a nonrandom pattern. The patient with Hunter syndrome reported by Winchester et al. (1992) was of the latter type. Goldenfum et al. (1996) demonstrated that both twins reported by Winchester et al. (1992) were heterozygous for a 1-bp deletion of cytosine at position 123 of their cDNA. The asymptomatic cotwin showed random X inactivation. </p><p>In analyzing 5 samples of families with MPS II, with a total of 158 cases, Machill et al. (1991) found that the mutant allele segregated in agreement with mendelian expectations for an X-linked recessive disorder, but the proportion of sporadic cases was significantly lower than expected under mutation-selection equilibrium. Heterogeneity among the samples was evident but was caused entirely by a sample of Ashkenazi families, in which the segregation pattern had previously been interpreted as suggesting prenatal selection in favor of the pathologic allele. In their analysis of the 5 samples by a maximum likelihood approach, Machill et al. (1991) found no suggestion of segregation distortion. The apparent deficiency of sporadic cases might be due to ascertainment bias. </p><p>In Ashkenazi Jews in Israel, Zlotogora et al. (1985) found no new mutations among the mothers of probands. Furthermore, they found a striking deviation in segregation of the Hunter and normal alleles in heterozygous females, with favoring of the former. In non-Ashkenazi populations, the rate of new mutations and the segregation ratio have been close to those expected (Archer et al., 1983; Tonnesen, 1984). Zlotogora et al. (1991) reported that 10 of the 12 Jewish families with Hunter syndrome in Israel were of Ashkenazi or Moroccan origin. They provided further evidence that in these families there is a paucity of new mutations and they confirmed the significant deviation of the segregation ratio between the Hunter gene and the normal allele among the offspring of heterozygous mothers and among the sibs of affected children. Selection in favor of the X chromosome carrying the Hunter allele was suggested. It has apparently not been observed in other ethnic groups. The explanation may lie in another closely linked gene such that the phenomenon is particular to the Jewish population. Another possibility is that the mutation itself gives an advantage to that chromosome. </p><p>Froissart et al. (1997) found evidence of germline and somatic mosaicism in the mother of a boy with an arg443-to-ter mutation (300823.0001). The mutation was found in a varying proportion of tissues tested (7% in leukocytes, lymphocytes and lymphoblastoid cells, and 22% in fibroblasts). The proband's sister carried the 'at risk' allele (as determined by haplotype analysis), but not the mutation. In sporadic cases of X-linked diseases, germline mosaicism of the proband's mother is difficult to exclude and should be considered in genetic counseling. </p><p>Sukegawa et al. (1998) reported a brother/sister pair with Hunter syndrome. Both had normal karyotypes. The sister was heterozygous for the R468L mutation (300823.0015) in genomic DNA, but homozygous for the allele in fibroblasts and lymphoblasts, resulting in relatively severe manifestations of the disease. Analysis of methylation patterns of the androgen receptor gene showed skewed X-chromosome inactivation of the paternal allele. </p>
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<strong>Mapping</strong>
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<span class="mim-text-font">
<p>Berg et al. (1968) concluded that the Hunter locus and the Xm locus (314900) are within measurable distance of each other on Xq28, the best estimate of the recombination fraction being 0.09. </p><p>Mossman et al. (1983) described a 3-year-old girl with typical Hunter syndrome. She had an apparently balanced reciprocal translocation between chromosomes X and 5 with the break in the former being between q26 and q27. The parents' karyotypes were normal. Pedigree analysis and normal enzyme levels in the mother's fibroblasts, serum, and hair roots indicated that the child had a new mutation. Location of the Hunter gene in the q26-q27 region and disruption of this gene in the origination of the translocation in this girl was proposed. The principle here is the same as that used to assign regionally the DMD locus (300377) and several others; the translocation chromosome is presumably the active one. Roberts et al. (1987, 1988, 1989) reexamined the case of Mossman et al. (1983) cytogenetically and concluded that the breakpoint was in Xq28 rather than being more proximal, as previously suggested. This finding is more in keeping with the linkage studies with DNA markers, which suggest location of the locus at Xq28. Furthermore, replication studies indicated that the normal X in this patient was preferentially inactivated. </p><p>Chase et al. (1986) concluded that the Hunter locus is distal to the factor IX locus (300746) inasmuch as the maximum lod score for the linkage of these loci was 0.424 at theta = 0.25, whereas that for the linkage of the Hunter syndrome and DX13 was 3.01 at theta = 0.1. DX13 maps to Xq28. From studies with DNA probes, Upadhyaya et al. (1985, 1986) suggested that the Hunter locus may be close to that for the fragile site at Xq27. </p><p>Le Guern et al. (1990) did a family linkage study using 4 polymorphic markers from the Xq27-q28 region. A maximum lod score of 6.57 at theta = 0.0 was obtained with DXS304. Furthermore, they showed, consistent with the finding of others, that the breakpoint of the X;5 translocation described by Mossman et al. (1983) is distal to DXS98 and proximal to DXS304. Thomas et al. (1989) extended studies of the X;5 translocation by study of cell hybrids containing the derivative X as their only human X chromosome material. By study of DNA markers and of a hybrid clone that apparently had undergone a secondary DNA rearrangement, they concluded that the 'IDS and FRAXA are probably located in the same subregion around Xq27.3.' </p><p>Couillin et al. (1990) described a method for isolating the 2 X;5 translocated derivative chromosomes in separate rodent-human cell hybrids. The method was based mainly on immunofluorescent screening using MIC2 (313470) and MIC5 (308840) antigenic markers. The MIC5 gene was found to be between IDS and G6PD (305900). Couillin et al. (1990) concluded that the fragile X site is proximal to IDS. Wilson et al. (1991) used an IDS cDNA clone to localize the gene to Xq28, distal to the fragile X site. The cDNA clone was also shown to span the X chromosome breakpoint in a female Hunter syndrome patient with an X;autosome translocation (Suthers et al., 1989). </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Diagnosis</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Tonnesen et al. (1983) found that cross-correction between the 2 cell populations of the Hunter syndrome heterozygote is inhibited by fructose 1-phosphate or mannose 6-phosphate. Intercellular uptake of lysosomal enzymes in cultured fibroblasts is prevented by addition of either mannose-6-phosphate or fructose-1-phosphate to the culture medium. They studied 25 obligatory carriers to determine the usefulness of fructose 1-phosphate as a means of carrier detection. In 23 carriers, (35)S-sulfate incorporation was significantly increased. In 1 carrier, incorporation was already increased before addition of fructose and in 1 carrier it was normal both before and after fructose. Tonnesen (1984) identified Hunter carriers by studying (35)S-sulfate accumulation in the presence and absence of fructose-1-phosphate. Petruschka et al. (1983) tested the Tonnesen technique by studying various mixtures of normal and Hunter cells in culture as well as obligatory carriers. They concluded that the method 'seems to be suitable for carrier detection.' Archer et al. (1983) concluded that carrier detection was best when hair-root analysis and serum enzyme levels were taken together. Daniele and Di Natale (1987) demonstrated crossreacting material in the serum and fibroblasts of Hunter patients. Zlotogora and Bach (1986) proposed that prenatal diagnosis of Hunter syndrome may be possible by measurement of iduronate sulfatase in the mother's serum. The level of IDS consistently rises in the serum of pregnant women. In pregnancies with Hunter-affected male fetuses, serum enzyme levels did not change. The normal increase occurs usually by the sixth to twelfth week. </p><p>Bakker et al. (1991) found that the IDS cDNA probe was partially deleted in 3 of 12 Dutch patients with Hunter syndrome. In 2 of the 3 patients, Southern blots showed the presence of a deletion junction fragment which could be used for highly reliable direct carrier detection in their families. Schroder et al. (1993) used different carrier detection tests, i.e., IDS activity in serum, sulfate incorporation in cultured skin fibroblasts, and RFLP analysis, in 13 unrelated families with 16 patients and 36 females at risk for MPS II. Twenty-nine females were confirmed as carriers, and in 5 women, the heterozygous state was excluded. The use of the intragenic IDS cDNA probes and flanking probes provided accuracy in carrier detection that was equal to or better than biochemical methods. Structural alterations were found in the DNA of 2 patients: one showed a major deletion including the whole coding sequence of the IDS gene; an aberrant Southern fragment occurred in the HindIII/pc2S15 blot of the other patient, suggesting a new HindIII restriction site by point mutation in an IDS gene intron. </p><p>Ben Simon-Schiff et al. (1993) confirmed the reliability of the serum assay of IDS activity in the identification of heterozygotes; the serum test correctly detected 11 of 12 of the first-degree relatives tested by the serum assay, 6 of 7 carriers, and 5 of 5 noncarriers. The only case with an apparent false negative result in the serum test was thought to represent an instance of germinal mosaicism. </p><p>In a family in which there was no surviving affected individual, Timms et al. (1998) described carrier testing using direct dye primer sequencing of PCR products to identify mixed bases in an obligate carrier. Two mixed bases were observed within exon 8 of the IDS gene. These resulted in a missense mutation and a nonsense mutation. Four additional female family members were screened for the same mutations, and none were found in any of these additional subjects, including in 1 who had been identified previously as a carrier by skin biopsy. Timms et al. (1998) concluded that this approach can be used to provide unambiguous information about a subject's carrier status, even in families in which the disorder is mild. </p><p>As a means of molecular diagnosis, Jonsson et al. (1995) developed a rapid method to sequence the entire iduronate 2-sulfatase coding region: PCR amplicons representing the IDS cDNA were sequenced with an automatic machine, and output was analyzed by computer-assisted interpretation of tracings. Mutations were found in 10 of 11 patients studied. Unique missense mutations were identified in 5 patients. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Clinical Management</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Braun et al. (1993) tested in vitro the correction of the enzyme defect in the Hunter syndrome, using an amphotropic retroviral vector containing the human IDS coding sequence. Lymphoblastoid cell lines from patients with Hunter syndrome were transduced with the vector and expressed high levels of IDS enzyme activity, 10- to 70-fold higher than normal human peripheral blood leukocytes or lymphoblastoid cell lines. The transduced cells failed to show accumulation of (35)SO4 into glycosaminoglycan, indicating that recombinant IDS enzyme participated in glycosaminoglycan metabolism. </p><p>Vellodi et al. (1999) reported the results of bone marrow transplantation performed in 10 patients with Hunter disease. The donor was an HLA-identical sib in 2 cases, an HLA-nonidentical relative in 6 cases, and a volunteer unrelated donor in 1 case. Details were not available in the last case. Only 3 patients had survived for more than 7 years post bone marrow transplant; of those, 1 died 11 years after bone marrow transplant. The authors suggested that this high mortality probably resulted from poor donor selection. In 2 who had survived long-term, there had been a steady progression of physical disability and mental handicap. One patient had maintained normal intellectual development, with only mild physical disability. </p><p>Wang et al. (2009) reported 2 unrelated boys with MPS II diagnosed at ages 3 years 9 months and 4 years 7 months, respectively. One had moderate mental retardation and aggressive behavior, whereas the other was cognitively normal without behavioral problems. Both also had white matter abnormalities and ventricular dilatation on brain MRI, which did not correlate with cognitive function. Treatment with intravenous enzyme replacement therapy (ERT) resulted in no change in brain MRI findings in either patient, indicating lack of progression. The findings suggested that ERT may halt or possibly improve brain MRI abnormalities in patients with MPS, even though ERT had previously been thought not to cross into the brain. Wang et al. (2009) offered some explanations, including lessening of somatic GAG accumulation, repair of damaged brain endothelium, and possibly small amounts of enzyme being able to permeate the brain. </p><p>Wraith et al. (2008) and Muenzer et al. (2009) reviewed the clinical management of patients with MPS II. </p><p>Wang et al. (2011) described the ACMG standards and guidelines for the diagnostic confirmation and management of presymptomatic individuals with lysosomal storage diseases. </p><p>Wikman-Jorgensen et al. (2020) performed a literature review to assess the safety and efficacy of ERT for the treatment of Hunter syndrome. The review included 42 articles, including 8 clinical trials, 21 observational studies, 12 clinical case reports, and 1 case-control study. All of the articles reported reduced urinary GAG content with ERT, and a dose response gradient was seen in the 3 studies in which different doses were evaluated. In 12 studies that evaluated the effect of ERT on distance walked on the 6 minute walk test, 8 reported an improvement in children and adults. Other findings with ERT included reduced liver and spleen size in 18 of 18 studies in which this outcome was reported, increased forced vital capacity on pulmonary function testing, reduction in the left ventricular mass index, and reduction in mortality. In all of the studies, improved quality of life with ERT was reported; however, a metaanalysis of the results was not possible due to the heterogeneous methodology across the studies. A clear effect of ERT was not observed on cognitive deterioration or growth. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Population Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Schaap and Bach (1980) reported a frequency of approximately 1 in 34,000 males born in Israel between 1967 and 1975. </p><p>In a questionnaire study in the United Kingdom, Young and Harper (1982) estimated the frequency of the Hunter syndrome as about 1 in 132,000 male births. The severe form was 3.38 times more frequent than the mild form. No increased incidence in Jews was noted. </p><p>In British Columbia, 6 cases of the Hunter syndrome were born between 1952 and 1986, giving a frequency of 1 in 110,950 live male births (Lowry et al., 1990). Chakravarti and Bale (1983) concluded that the high frequency of Hunter disease in Israeli Jews (Goodman, 1979) is compatible with genetic drift. </p><p>Using multiple ascertainment sources, Nelson et al. (2003) estimated the incidence rate for mucopolysaccharidoses in western Australia for the period 1969 to 1996. An incidence of approximately 1 in 320,000 live births (1 in 165,000 male live births) was obtained for Hunter syndrome. </p><p>Lin et al. (2009) analyzed the incidence of MPS in Taiwan between 1984 and 2004 and found that the combined birth incidence for all MPS cases was 2.04 per 100,000 live births. MPS II (Hunter syndrome) had the highest calculated birth incidence (1.07 per 100,000 live births), comprising 52% of all MPS cases diagnosed. Although the overall incidence of MPS in Taiwan was consistent with reports from Western populations, Lin et al. (2009) noted that in contrast to reports of a higher incidence of MPS I in most Western populations, their study showed a higher incidence of MPS II in Taiwan. </p><p>Khan et al. (2017) analyzed the epidemiology of the mucopolysaccharidoses in Japan and Switzerland and compared them to similar data from other countries. Information for Japan was collected between 1982 and 2009, and 467 cases with MPS were identified. The combined birth prevalence was 1.53 per 100,000 live births. The highest birth prevalence was 0.84 for MPS II, accounting for 55% of all MPS. MPS I (see 607014), III (see 252900), and IV (see 253000) accounted for 15%, 16%, and 10%, respectively. MPS VI (253200) and VII (253220) were more rare and accounted for 1.7% and 1.3%, respectively. A retrospective epidemiologic data collection was performed in Switzerland between 1975 and 2008 (34 years), and 41 living MPS patients were identified. The combined birth prevalence was 1.56 per 100,000 live births. The highest birth prevalence was 0.46 for MPS II, accounting for 29% of all MPS. MPS I, III, and IV accounted for 12%, 24%, and 24%, respectively. As seen in the Japanese population, MPS VI and VII were more rare and accounted for 7.3% and 2.4%, respectively. The high birth prevalence of MPS II in Japan was comparable to that seen in other East Asian countries where this MPS accounted for approximately 50% of all forms of MPS. Birth prevalence was also similar in some European countries (Germany, Northern Ireland, Portugal and the Netherlands) although the prevalence of other forms of MPS was also reported to be higher in these countries. </p><p>Koto et al. (2021) surveyed hospitals in Japan for information about patients with lysosomal storage diseases (LSDs) treated between 2013-2016 and 2018-2019. MPS II was the second most common LSD after Fabry disease (301500), with 103 patients identified, of whom 31.1% had the severe form, 20.4% had the attenuated form, and 48.5% had an unknown form. When these data were extrapolated across Japan, Koto et al. (2021) estimated that there were 275 patients with MPS II. They calculated a birth prevalence in Japan of 0.38 per 100,000. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Wilson et al. (1991) found a deletion or gene rearrangement in 7 of 23 Hunter patients of Australian and British origin. In 2 of 14 unrelated German MPS II patients, structural alteration of the IDS gene was found by Southern analysis using an IDS cDNA clone as a probe. In one of these patients, a severely affected male, no Southern fragments were detected. </p><p>In 2 unrelated patients with complete deletion of the IDS gene, Wraith et al. (1991) reported that the phenotype was that of very severe Hunter syndrome. In addition, both had features not commonly seen in MPS II, namely, early onset of seizures in one patient and ptosis in the other. </p><p>In 12 patients, Bunge et al. (1992) used single-strand conformation polymorphism analysis for mutation analysis. Missense or nonsense mutations and deletions or insertions of a small number of basepairs were found in most; probably only about 20% of Hunter patients have complete deletion or gross structural alteration of the IDS gene. The broad clinical variability among Hunter patients is apparently a reflection of extensive molecular heterogeneity. </p><p>Palmieri et al. (1992) isolated a 1.2-Mb YAC contig spanning the IDS gene. Several putative CpG islands were identified in the region, suggesting the presence of other genes. Southern analysis of DNA from 25 unrelated Italian MPS II patients uncovered 4 with deletions or rearrangements in the IDS gene. DNA from a patient with a translocation breakpoint in the gene permitted orientation of the contig in relation to the centromere. </p><p>Steen-Bondeson et al. (1992) investigated the occurrence of rearrangements and deletions of the IDS gene in a Southern analysis of 46 unrelated MPS2 patients of different ethnic origins using a cDNA clone containing the entire IDS gene as a probe. Structural alterations were found in DNA from 9 patients, 2 of whom showed large deletions including all coding sequences of the gene. The distal and proximal breakpoints of these deletions were determined by hybridization of markers flanking the IDS gene. Seven of the observed alterations constituted major rearrangements of the gene. Six of these rearrangements showed similar or identical patterns by Southern analysis, suggestive of a region prone to structural alterations within the IDS gene. Steen-Bondeson et al. (1992) also demonstrated the potential use of the IDS probe for carrier detection in families with a rearranged IDS gene. </p><p>Froissart et al. (1993) described 2 patients who appeared to have complete deletion of the IDS gene. It appeared that these patients had a more severe form of Hunter syndrome. </p><p>From a study of a total of 26 cases, Bunge et al. (1993) found that about 20% of patients have deletions of the whole IDS gene or other major structural alterations. In about 23% of cases, deletion of 1, 2, or 3 basepairs was found, while the remaining patients, about 57%, carried point mutations predicting amino acid replacement, premature termination of translation, or aberrant splicing. </p><p>Hopwood et al. (1993) reviewed mutations in the IDS gene in Hunter syndrome. From the group of 319 patients thus far studied by Southern analysis, 14 had full deletion of the gene and 48 had partial deletion or other gross rearrangements. All patients with full deletions or gross rearrangements had severe clinical presentations. In a total of 32 patients, 29 different 'small' mutations had been characterized: 4 nonsense and 13 missense mutations, 7 different small deletions from 1 to 3 bp, with most leading to a frameshift and premature chain termination, and 5 different splice site mutations also leading to small insertions or deletions in the mRNA. A 60-bp deletion that resulted from the creation of a new donor splice site was observed in 5 unrelated patients with relatively mild clinical phenotypes. </p><p>Sukegawa et al. (1995) described 8 new examples of point mutations in the IDS gene in Japanese Hunter syndrome patients exhibiting various degrees of severity. </p><p>Bondeson et al. (1995) identified an IDS pseudogene, which they designated IDS2, located within 90 kb telomeric of the IDS gene. They showed that this region is involved in a recombination event with the primary IDS gene in about 13% of patients with the Hunter syndrome. Analysis of the resulting rearrangement at the molecular level showed that these patients had suffered a recombination event that resulted in a disruption of the IDS gene in intron 7 with an inversion of the intervening DNA. All 6 patients with a similar type of rearrangement showed recombination between intron 7 of the IDS gene and sequences close to exon 3 of the IDS2 locus, implying that these regions are hotspots for recombination. Nucleotide sequencing showed that the inversion is caused by recombination between homologous sequences present in the IDS gene and the IDS2 locus. No detectable deletions or insertions were observed as a consequence of the recombination. The IDS2 pseudogene contains sequences that are related to exons 2 and 3 as well as introns 2, 3, and 7 of the IDS gene. An example of a similar inversion caused by homologous recombination is that involving intron 22 of the factor VIII gene (F8; 300841) causing severe hemophilia A (306700). In the case of the F8 gene, the inversions occur almost exclusively in the male germ cells. It has therefore been hypothesized that mispairing leading to inversion is inhibited by pairing of the X chromosomes in the female germ cells. Interestingly, both the F8 gene and the IDS gene are located in Xq28, a distal part of the X chromosome that is generally unpaired in males. Bondeson et al. (1995) provided additional information concerning the IDS2 gene. </p><p>Birot et al. (1996) described a patient with Hunter syndrome in whom an exchange between the IDS gene and pseudogene through interchromosomal recombination had apparently caused internal deletion of exons 4, 5, 6, and 7. In the rearranged gene, the junction intron contained pseudogene intron 3- and intron 7-related sequences. </p><p>Rathmann et al. (1996) identified IDS mutations in 31 families/patients with MPS II. Twenty mutations were novel and unique and another was novel but was found in 3 unrelated patients. One of the mutations detected was of special interest as it is an A-to-G substitution in an intron far from the coding region that is deleterious because it creates a new 5-prime splice donor site that results in the inclusion of a 78-bp intronic sequence (300823.0014). The authors analyzed a total of 101 point mutations in the coding region and found that they tended to be more frequent in exons 3, 8, and 9. CpG dinucleotides were involved in 47% of the point mutations, of which G:C-to-A:T transitions constituted nearly 80%. Almost all recurrent point mutations involved CpG sites. Analysis of a collection of 50 families studied by this group revealed that mutations occurred more frequently in male meioses; they estimated the male-to-female ratio to be between 3.76 and 6.3. </p><p>Froissart et al. (1998) studied 70 unrelated Hunter patients and found a mutation in each. There was striking molecular heterogeneity. Large gene rearrangements were identified in 14 patients. In the 56 other patients, 43 different mutations were identified, and 31 had not previously been described. Since only a few mutations were present in several patients, genotype/phenotype correlations were difficult. The mother was not found to be a carrier in 5 among 44 sporadic cases. Haplotype analysis demonstrated a high frequency of mutations in male meiosis. </p><p>Isogai et al. (1998) characterized 25 different small mutations in the IDS gene in a series of 43 Japanese patients with Hunter disease. As in other series, 3 different mutations in codon 468 of exon 9 were found: arg468 to trp (309900.0012), arg468 to gln (309900.0013), arg468 to leu (309900.0015). All 3 mutations were associated with a severe phenotype. </p><p>Timms et al. (1998) described a patient with features of moderate to severe Hunter syndrome and a 178-bp deletion upstream of IDS exon 1 spanning a predicted promoter element. Sequencing of all 9 IDS exons failed to show any additional mutations within the coding region or in intron/exon boundaries. The 178-bp deletion was flanked by 2 13-bp direct repeats and potential DNA topoisomerase II recognition sites. These findings suggested to Timms et al. (1998) nonhomologous recombination as a possible mechanism for the deletion. Expression studies detected no IDS transcripts. </p><p>In a study of 31 Spanish families with Hunter disease, Gort et al. (1998) found 22 novel small mutations (7 reported previously by the same group) and 4 large deletions or rearrangements. This brought the number of separate IDS mutations that had been reported to that time to nearly 150. Li et al. (1999) provided yet more evidence of the molecular heterogeneity of this condition by identifying 17 mutations in 18 unrelated patients with MPS2. The mutations included 7 missense mutations, 5 small deletions, 2 insertions, 2 splice site mutations, and an intragenic deletion of exons 4, 5, 6, and 7. Nine of the small mutations were novel. </p><p>In 36 Russian patients with Hunter syndrome, Karsten et al. (1998) found 25 different mutations, of which 15 were novel. Most of the missense mutations resulted in intermediate or severe phenotypes. </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>In a review, Muenzer et al. (2009) noted that a paucity of common and recurrent mutations in the IDS gene makes genotype/phenotype correlations difficult. They stated that complete deletions and complex rearrangements of the IDS gene always result in a severe phenotype. Although 3 mutations in codon 468 of exon 9 (300823.0012, 300823.0013, 300823.0015) have been associated with a severe phenotype, each has also been reported in patients with attenuated phenotypes. Similarly, the 1122C-T transition (300823.0002), which creates an alternate splice site with the loss of 20 amino acids, is primarily associated with an attenuated phenotype. </p><p><strong><em>Contiguous Gene Deletion on Xq28 Involving the IDS Gene</em></strong></p><p>
In a patient with classic severe Hunter syndrome who also suffered from epileptic seizures, Steen-Bondeson et al. (1992) identified a deletion with a proximal breakpoint between DXS295 and DXS296. They noted that epileptic seizures were also described in 2 patients reported by Wilson et al. (1991) and Wraith et al. (1991) with a complete deletion of the IDS gene. A comparison of the breakpoints in the 3 patients suggested that a gene or genes located in the vicinity to the IDS gene may be involved in the development of epilepsy. </p><p>Birot et al. (1996) described a family with a cytogenetically evident deletion in Xq27.2-q28 that removed the IDS and FMR1 genes. This was said to be the largest deletion in this region of the X chromosome identified in a male patient, indicating that absence of any of the genes in this region would not be lethal. </p><p>Timms et al. (1997) used genomic DNA sequencing to identify several new genes in the IDS region. DNA deletion patients with atypical symptoms were analyzed to determine whether these atypical symptoms could be due to involvement of these other loci. The occurrence of seizures in 2 individuals correlated with a deletion extending proximal to IDS, up to and including part of the FMR2 locus (309548). Other (nonseizure) symptoms were associated with distal deletions. In addition, a group of patients with no variant symptoms, and a characteristic rearrangement involving a recombination between the IDS gene and an adjacent IDS pseudogene, showed normal expression of loci distal to IDS. Timms et al. (1997) concluded that together these results identified FMR2 as a candidate gene for seizures, when mutated along with IDS. </p><p>Karsten et al. (1997) noted that the region of the IDS gene, in addition to the IDS2 gene that harbors sequences homologous to exons 2 and 3 and introns 2, 3, and 7, contains several novel genes (e.g., genes W, X, and Y). In addition, a neighboring region has undergone a duplication and exists in an inverted version on the telomeric side of IDS. Karsten et al. (1997) identified 2 distinct deletions separated by 30 kb in a patient with Hunter syndrome. One deletion included exons 5 and 6 of the IDS gene; the second deletion included exons 3 and 4 of the W gene, located telomeric of the IDS gene. Both deletions were the result of nonhomologous (illegitimate) recombination events between short direct repeats at the deletion breakpoints. Lagerstedt et al. (2000) analyzed a 43.6-kb deletion in a patient with Hunter syndrome and found a fusion transcript including sequences from the gene W and the IDS gene. Surprisingly, a similar but longer fusion transcript containing exons 2-4 of gene W and exons 4-9 of the IDS gene could be detected in RNA of normal cell lines originating from various tissues. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Animal Model</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Wilkerson et al. (1998) described Hunter syndrome in a Labrador retriever. The findings included coarse facial features, macrodactyly, unilateral corneal dystrophy (an atypical feature for type II mucopolysaccharidosis), generalized osteopenia, progressive neurologic deterioration, and a positive urine spot test for acid mucopolysaccharides. Deficiency in iduronate-2-sulfatase was demonstrated in cultured dermal fibroblasts. Hair root analysis for IDS showed that the dam (mother) was a carrier and that a phenotypically normal male littermate was normal. </p><p>Garcia et al. (2007) observed that male Ids-null mice showed increased urinary GAG excretion from 4 weeks of age through their life span. Tissue GAG levels were increased by 7 weeks of age. The mutant mice also showed hepatomegaly, splenomegaly, and enlargement of other organs compared to wildtype mice. Other features included coarse fur and sporadic alopecia, joint limitation, curved digits, abnormal skull development, decreased activity, and significantly decreased life span. Radiographic studies showed sclerosis and enlargement of the skull and appendicular bones. There was periosteal bone formation in the distal tibiae and calcification of the calcaneus tendon. Histologic studies revealed diffuse presence of foamy, vacuolated cell types in multiple organs. Garcia et al. (2007) noted the similarities to human disease. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>History</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Neufeld et al. (1977) described 2 families, each with a girl clinically affected with the Hunter syndrome and with profound deficiency of iduronate 2-sulfatase. The patients were karyotypically normal and had normal fathers. Cloning of the mothers' fibroblasts did not show the mosaicism expected of the X-linked disease. Homozygosity for a previously unsuspected autosomal recessive gene for iduronate sulfatase was considered the most likely explanation, although heterozygosity for the X-linked gene and subsequent selection could not be completely excluded. Studies of the enzyme at the molecular level and of complementation in somatic cell hybrids are required to distinguish between these possibilities. The mutation in the 2 families was presumably different (although perhaps allelic) because it took the severe form in one family and the mild form in the other. Strong support for autosomal recessive inheritance came from the fact that the parents were first cousins in one family and had ancestors from the same ethnic group and same small town in the other family. Neufeld (1981) suggested that these cases may have been instances of multiple sulfatase deficiency (272200) in which the deficiency of iduronate sulfatase is particularly striking. In 1 of the families, however, this did not appear to be the explanation. </p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>See Also:</strong>
</span>
</h4>
<span class="mim-text-font">
Bach et al. (1973); Booth and Nadler (1974); Brown et al. (1982);
Clarke et al. (1990); Danes and Bearn (1967); Dean et al. (1979);
Gerich (1969); Hunter (1917); Kleijer et al. (1979); Migeon et al.
(1977); Nwokoro and Neufeld (1979); Ockerman and Kohlin (1968);
Schachern et al. (1984); Tonnesen et al. (1982); Upadhyaya et al.
(1985); Van Pelt (1960); Wehnert et al. (1992); Wiesmann et al.
(1980); Yatziv et al. (1977); Young and Harper (1979); Yutaka et al.
(1978); Zlotogora and Bach (1984)
</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">
Archer, I. M., Young, I. D., Rees, D. W., Oladimeji, A., Wusteman, F. S., Harper, P. S.
<strong>Carrier detection in Hunter syndrome.</strong>
Am. J. Med. Genet. 16: 61-69, 1983.
[PubMed: 6227239]
[Full Text: https://doi.org/10.1002/ajmg.1320160111]
</p>
</li>
<li>
<p class="mim-text-font">
Bach, G., Eisenberg, F., Jr., Cantz, M., Neufeld, E. F.
<strong>The defect in the Hunter syndrome: deficiency of sulfoiduronate sulfatase.</strong>
Proc. Nat. Acad. Sci. 70: 2134-2138, 1973.
[PubMed: 4269173]
[Full Text: https://doi.org/10.1073/pnas.70.7.2134]
</p>
</li>
<li>
<p class="mim-text-font">
Bakker, E., Kneppers, A., Deutz-Terlouw, P., Goor, J., Poorthuis, B., Kleyer, W., Niermeijer, M., Kamp, J., Hopwood, J., Ommen, G.
<strong>Partial gene deletions in 3 out of 12 Dutch Hunter patients: direct and indirect carrier detection by DNA-analysis. (Abstract)</strong>
Cytogenet. Cell Genet. 58: 2055-2056, 1991.
</p>
</li>
<li>
<p class="mim-text-font">
Ballenger, C. E., Swift, T. R., Leshner, R. T., El Gammal, T. A., McDonald, T. F.
<strong>Myelopathy in mucopolysaccharidosis type II (Hunter syndrome).</strong>
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[PubMed: 107796]
</p>
</li>
<li>
<p class="mim-text-font">
Ochiai, T., Ito, K., Okada, T., Chin, M., Shichino, H., Mugishima, H.
<strong>Significance of extensive Mongolian spots in Hunter&#x27;s syndrome.</strong>
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[PubMed: 12828746]
[Full Text: https://doi.org/10.1046/j.1365-2133.2003.05317.x]
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Ockerman, P. A., Kohlin, P.
<strong>Glycosidases in skin and plasma in Hunter&#x27;s syndrome: abnormality of a beta-galactosidase in skin.</strong>
Acta Paediat. Scand. 57: 281-284, 1968.
[PubMed: 4236601]
[Full Text: https://doi.org/10.1111/j.1651-2227.1968.tb07292.x]
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Palmieri, G., Capra, V., Romano, G., D'Urso, M., Johnson, S., Schlessinger, D., Morris, P., Hopwood, J., Di Natale, P., Gatti, R., Ballabio, A.
<strong>The iduronate sulfatase gene: isolation of a 1.2-Mb YAC contig spanning the entire gene and identification of heterogeneous deletions in patients with Hunter syndrome.</strong>
Genomics 12: 52-57, 1992.
[PubMed: 1733863]
[Full Text: https://doi.org/10.1016/0888-7543(92)90405-h]
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Petruschka, L., Machill, G., Wehnert, M., Seidlitz, G., Knapp, A.
<strong>Reliability of the Tonnesen technique for the identification of Hunter carriers.</strong>
Hum. Genet. 64: 404-406, 1983.
[PubMed: 6413387]
[Full Text: https://doi.org/10.1007/BF00292377]
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Rathmann, M., Bunge, S., Beck, M., Kresse, H., Tylki-Szymanska, A., Gal, A.
<strong>Mucopolysaccharidosis type II (Hunter syndrome): mutation &#x27;hot spots&#x27; in the iduronate-2-sulfatase gene.</strong>
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[PubMed: 8940265]
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Roberts, S. H., Upadhyaya, M., Sarfarazi, M., Harper, P. S.
<strong>Further evidence localizing the gene for Hunter syndrome to the most distal band of the X chromosome long arm. (Abstract)</strong>
Cytogenet. Cell Genet. 46: 682 only, 1987.
</p>
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Roberts, S. H., Upadhyaya, M., Sarfarazi, M., Harper, P. S.
<strong>Further evidence localising the gene for Hunter syndrome to Xq28. (Abstract)</strong>
J. Med. Genet. 25: 280 only, 1988.
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Roberts, S. H., Upadhyaya, M., Sarfarazi, M., Harper, P. S.
<strong>Further evidence localising the gene for Hunter&#x27;s syndrome to the distal region of the X chromosome long arm.</strong>
J. Med. Genet. 26: 309-313, 1989.
[PubMed: 2499679]
[Full Text: https://doi.org/10.1136/jmg.26.5.309]
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[Full Text: https://doi.org/10.1016/s0190-9622(98)70280-4]
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<strong>Incidence of mucopolysaccharidoses in Israel: is Hunter disease a &#x27;Jewish disease&#x27;?</strong>
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[PubMed: 6821579]
[Full Text: https://doi.org/10.1007/BF00295699]
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<strong>Mucopolysaccharidosis I-H (Hurler&#x27;s syndrome) and human temporal bone histopathology.</strong>
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[PubMed: 6422830]
[Full Text: https://doi.org/10.1177/000348948409300115]
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Schroder, W., Petruschka, L., Wehnert, M., Zschiesche, M., Seidlitz, G., Hopwood, J. J., Herrmann, F. H.
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Steen-Bondeson, M.-L., Dahl, N., Tonnesen, T., Kleijer, W. J., Seidlitz, G., Gustavson, K.-H., Wilson, P. J., Morris, C. P., Hopwood, J. J., Pettersson, U.
<strong>Molecular analysis of patients with Hunter syndrome: implication of a region prone to structural alterations within the IDS gene.</strong>
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[Full Text: https://doi.org/10.1093/hmg/1.3.195]
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[Full Text: https://doi.org/10.1111/j.1399-0004.1998.tb02654.x]
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<strong>Mucopolysaccharidosis type II (Hunter disease): identification and characterization of eight point mutations in the iduronate-2-sulfatase gene in Japanese patients.</strong>
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[PubMed: 7581397]
[Full Text: https://doi.org/10.1002/humu.1380060206]
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Suthers, G. K., Callen, D. F., Hyland, V. J., Kozman, H. M., Baker, E., Eyre, H., Harper, P. S., Roberts, S. H., Hors-Cayla, M. C., Davies, K. E., Bell, M. V., Sutherland, G. R.
<strong>A new DNA marker tightly linked to the fragile X locus (FRAXA).</strong>
Science 246: 1298-1300, 1989.
[PubMed: 2573953]
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Thomas, N. S. T., Roberts, S. H., Upadhyaya, M., Knight, S., Harper, P. S.
<strong>Physical localization of the X;autosomal translocation breakpoint from a girl expressing Hunter syndrome using Xq27-q28 DNA markers. (Abstract)</strong>
Cytogenet. Cell Genet. 51: 1090 only, 1989.
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Timms, K. M., Bondeson, M.-L., Ansari-Lari, M. A., Lagerstedt, K., Muzny, D. M., Dugan-Rocha, S. P., Nelson, D. L., Pettersson, U., Gibbs, R. A.
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Hum. Molec. Genet. 6: 479-486, 1997.
[PubMed: 9147653]
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Timms, K. M., Edwards, F. J., Belmont, J. W., Yates, J. R. W., Gibbs, R. A.
<strong>Reassessment of biochemically determined Hunter syndrome carrier status by DNA testing.</strong>
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[PubMed: 9719370]
[Full Text: https://doi.org/10.1136/jmg.35.8.646]
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<p class="mim-text-font">
Timms, K. M., Huckett, L. E., Belmont, J. W., Shapira, S. K., Gibbs, R. A.
<strong>DNA deletion confined to the iduronate-2-sulfatase promoter abolishes IDS gene expression.</strong>
Hum. Mutat. 11: 121-126, 1998.
[PubMed: 9482575]
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1998)11:2&lt;121::AID-HUMU4&gt;3.0.CO;2-M]
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<p class="mim-text-font">
Tonnesen, T., Guttler, F., Lykkelund, C.
<strong>Reliability of the use of fructose 1-phosphate to detect Hunter cells in fibroblast-cultures of obligate carriers of the Hunter syndrome.</strong>
Hum. Genet. 64: 371-375, 1983.
[PubMed: 6225723]
[Full Text: https://doi.org/10.1007/BF00292369]
</p>
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<p class="mim-text-font">
Tonnesen, T., Lykkelund, C., Guttler, F.
<strong>Diagnosis of Hunter&#x27;s syndrome carriers; radioactive sulphate incorporation into fibroblasts in the presence of fructose 1-phosphate.</strong>
Hum. Genet. 60: 167-171, 1982.
[PubMed: 6210620]
[Full Text: https://doi.org/10.1007/BF00569706]
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<p class="mim-text-font">
Tonnesen, T.
<strong>The use of fructose 1-phosphate to detect Hunter heterozygotes in fibroblast cultures from high-risk carriers.</strong>
Hum. Genet. 66: 212-216, 1984.
[PubMed: 6425196]
[Full Text: https://doi.org/10.1007/BF00286603]
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Tsuzaki, S., Matsuo, N., Nagai, T., Osano, M., Orii, T.
<strong>An unusually mild variant of Hunter&#x27;s syndrome in a 14-year-old boy: normal growth and development.</strong>
Acta Paediat. Scand. 76: 844-846, 1987.
[PubMed: 3116824]
[Full Text: https://doi.org/10.1111/j.1651-2227.1987.tb10577.x]
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Upadhyaya, M., Bamforth, S., Harper, P. S., Sarfarazi, M., Thomas, N. S. T., Shaw, D. J., Meredith, A. L., Rees, D., Davies, K., Young, I. D.
<strong>Localization of Hunter syndrome gene by genetic linkage analysis. (Abstract)</strong>
Cytogenet. Cell Genet. 40: 765 only, 1985.
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Upadhyaya, M., Bamforth, S., Young, I., Thomas, N., Sarfarazi, M., Davies, K., Harper, P. S.
<strong>Hunter&#x27;s syndrome: evidence supporting a location on the distal part of the X chromosome long arm. (Abstract)</strong>
J. Med. Genet. 22: 394-395, 1985.
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Upadhyaya, M., Sarfarazi, M., Bamforth, J. S., Thomas, N. S. T., Oberle, I., Young, I., Harper, P. S.
<strong>Localisation of the gene for Hunter syndrome on the long arm of X chromosome.</strong>
Hum. Genet. 74: 391-398, 1986.
[PubMed: 2878868]
[Full Text: https://doi.org/10.1007/BF00280492]
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<p class="mim-text-font">
Van Pelt, J. F.
<strong>Gargoylism.</strong>
Thesis: Nijmegen (pub.) 1960.
</p>
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<p class="mim-text-font">
Vellodi, A., Young, E., Cooper, A., Lidchi, V., Winchester, B., Wraith, J. E.
<strong>Long-term follow-up following bone marrow transplantation for Hunter disease.</strong>
J. Inherit. Metab. Dis. 22: 638-648, 1999.
[PubMed: 10399096]
[Full Text: https://doi.org/10.1023/a:1005525931994]
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Wang, R. Y., Bodamer, O. A., Watson, M. S., Wilcox, W. R.
<strong>Lysosomal storage diseases: diagnostic confirmation and management of presymptomatic individuals.</strong>
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Molec. Genet. Metab. 98: 406-411, 2009.
[PubMed: 19748810]
[Full Text: https://doi.org/10.1016/j.ymgme.2009.07.015]
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Wehnert, M., Hopwood, J. J., Schroder, W., Herrmann, F. H.
<strong>Structural gene aberrations in mucopolysaccharidosis II (Hunter).</strong>
Hum. Genet. 89: 430-432, 1992.
[PubMed: 1352274]
[Full Text: https://doi.org/10.1007/BF00194316]
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Wiesmann, U. N., Spycher, M. A., Meier, C., Liebaers, I., Herschkowitz, N.
<strong>Prenatal mucopolysaccharidosis II (Hunter): a pathogenetic study.</strong>
Pediat. Res. 14: 749-756, 1980.
[PubMed: 6770331]
[Full Text: https://doi.org/10.1203/00006450-198005000-00008]
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Wikman-Jorgensen, P. E., Lopez Amoros, A., Peris Garcia, J., Esteve Atienzar, P. J., Canizares Navarro, R., Arsenio Tomas, M. L., Segui Ripoll, J. M., Bonet, D., Esteban-Giner, M. J., Robert, J., Giner-Galvan, V.
<strong>Enzyme replacement therapy for the treatment of Hunter disease: a systematic review with narrative synthesis and meta-analysis.</strong>
Molec. Genet. Metab. 131: 206-210, 2020.
[PubMed: 32773276]
[Full Text: https://doi.org/10.1016/j.ymgme.2020.07.005]
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Wilkerson, M. J., Lewis, D. C., Marks, S. L., Prieur, D. J.
<strong>Clinical and morphologic features of mucopolysaccharidosis type II in a dog: naturally occurring model of Hunter syndrome.</strong>
Vet. Path. 35: 230-233, 1998.
[PubMed: 9598589]
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Wilson, P. J., Suthers, G. K., Callen, D. F., Baker, E., Nelson, P. V., Cooper, A., Wraith, J. E., Sutherland, G. R., Morris, C. P., Hopwood, J. J.
<strong>Frequent deletions at Xq28 indicate genetic heterogeneity in Hunter syndrome.</strong>
Hum. Genet. 86: 505-508, 1991.
[PubMed: 1901826]
[Full Text: https://doi.org/10.1007/BF00194643]
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Winchester, B., Young, E., Geddes, S., Genet, S., Hurst, J., Middleton-Price, H., Williams, N., Webb, M., Habel, A., Malcolm, S.
<strong>Female twin with Hunter disease due to nonrandom inactivation of the X-chromosome: a consequence of twinning.</strong>
Am. J. Med. Genet. 44: 834-838, 1992.
[PubMed: 1481858]
[Full Text: https://doi.org/10.1002/ajmg.1320440625]
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Wraith, J. E., Cooper, A., Thornley, M., Wilson, P. J., Nelson, P. V., Morris, C. P., Hopwood, J. J.
<strong>The clinical phenotype of two patients with a complete deletion of the iduronate-2-sulphatase gene (mucopolysaccharidosis II--Hunter syndrome).</strong>
Hum. Genet. 87: 205-206, 1991.
[PubMed: 1906048]
[Full Text: https://doi.org/10.1007/BF00204183]
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<strong>Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy.</strong>
Europ. J. Pediat. 167: 267-277, 2008.
[PubMed: 18038146]
[Full Text: https://doi.org/10.1007/s00431-007-0635-4]
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Yatziv, S., Erickson, R. P., Epstein, C. J.
<strong>Mild and severe Hunter syndrome (MPS II) within the same sibships.</strong>
Clin. Genet. 11: 319-326, 1977.
[PubMed: 140775]
[Full Text: https://doi.org/10.1111/j.1399-0004.1977.tb01323.x]
</p>
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<p class="mim-text-font">
Young, I. D., Harper, P. S.
<strong>Long-term complications in Hunter&#x27;s syndrome.</strong>
Clin. Genet. 16: 125-132, 1979.
[PubMed: 113150]
[Full Text: https://doi.org/10.1111/j.1399-0004.1979.tb00861.x]
</p>
</li>
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<p class="mim-text-font">
Young, I. D., Harper, P. S.
<strong>Incidence of Hunter&#x27;s syndrome. (Letter)</strong>
Hum. Genet. 60: 391-392, 1982.
[PubMed: 6809596]
[Full Text: https://doi.org/10.1007/BF00569230]
</p>
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<p class="mim-text-font">
Yund, B., Rudser, K., Ahmed, A., Kovac, V., Nestrasil, I., Raiman, J., Mamak, E., Harmatz, P., Steiner, R., Lau, H., Vekaria, P., Wozniak, J. R., Lim, K. O., Delaney, K., Whitley, C., Shapiro, E. G.
<strong>Cognitive, medical, and neuroimaging characteristics of attenuated mucopolysaccharidosis type II.</strong>
Molec. Genet. Metab. 114: 170-177, 2015.
[PubMed: 25541100]
[Full Text: https://doi.org/10.1016/j.ymgme.2014.12.299]
</p>
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<li>
<p class="mim-text-font">
Yutaka, T., Fluharty, A. L., Stevens, R. L., Kihara, H.
<strong>Iduronate sulfatase analysis of hair roots for identification of Hunter syndrome heterozygotes.</strong>
Am. J. Hum. Genet. 30: 575-582, 1978.
[PubMed: 106723]
</p>
</li>
<li>
<p class="mim-text-font">
Zlotogora, J., Bach, G.
<strong>Heterozygote detection in Hunter syndrome.</strong>
Am. J. Med. Genet. 17: 661-665, 1984.
[PubMed: 6424473]
[Full Text: https://doi.org/10.1002/ajmg.1320170317]
</p>
</li>
<li>
<p class="mim-text-font">
Zlotogora, J., Bach, G.
<strong>Hunter syndrome: prenatal diagnosis in maternal serum.</strong>
Am. J. Hum. Genet. 38: 253-260, 1986.
[PubMed: 3080875]
</p>
</li>
<li>
<p class="mim-text-font">
Zlotogora, J., Schaap, T., Zeigler, M., Bach, G.
<strong>Hunter syndrome among Ashkenazi Jews in Israel; evidence for prenatal selection favoring the Hunter allele.</strong>
Hum. Genet. 71: 329-332, 1985.
[PubMed: 3935563]
[Full Text: https://doi.org/10.1007/BF00388459]
</p>
</li>
<li>
<p class="mim-text-font">
Zlotogora, J., Schaap, T., Zeigler, M., Bach, G.
<strong>Hunter syndrome in Jews in Israel: further evidence for prenatal selection favoring the Hunter allele.</strong>
Hum. Genet. 86: 531-533, 1991.
[PubMed: 1901828]
[Full Text: https://doi.org/10.1007/BF00194650]
</p>
</li>
</ol>
<div>
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</div>
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Contributors:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Hilary J. Vernon - updated : 09/13/2021<br>Hilary J. Vernon - updated : 04/06/2021<br>Ada Hamosh - updated : 05/29/2018<br>Jane Kelly - updated : 4/18/2016<br>Ada Hamosh - updated : 2/25/2015<br>Ada Hamosh - updated : 10/4/2012<br>Cassandra L. Kniffin - updated : 8/16/2010<br>Marla J. F. O&#x27;Neill - updated : 10/30/2009<br>Cassandra L. Kniffin - updated : 2/29/2008<br>Victor A. McKusick - updated : 6/15/2004<br>Victor A. McKusick - updated : 1/5/2004<br>Gary A. Bellus - updated : 9/4/2003<br>Victor A. McKusick - updated : 6/23/2003<br>Victor A. McKusick - updated : 1/14/2002<br>Victor A. McKusick - updated : 4/19/2000<br>Ada Hamosh - updated : 7/15/1999<br>Victor A. McKusick - updated : 6/17/1999<br>Michael J. Wright - updated : 2/12/1999<br>Victor A. McKusick - updated : 1/21/1999<br>Michael J. Wright - updated : 11/16/1998<br>Victor A. McKusick - updated : 10/13/1998<br>Victor A. McKusick - updated : 9/15/1998<br>Ada Hamosh - updated : 8/13/1998<br>Victor A. McKusick - updated : 6/12/1998<br>Victor A. McKusick - updated : 3/26/1998<br>Victor A. McKusick - updated : 11/26/1997<br>Victor A. McKusick - updated : 8/26/1997<br>Victor A. McKusick - updated : 4/15/1997<br>Victor A. McKusick - updated : 3/6/1997<br>Victor A. McKusick - updated : 2/18/1997<br>Victor A. McKusick - updated : 2/7/1997
</span>
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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 : 6/4/1986
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