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Entry
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- #614389 - PREGNANCY LOSS, RECURRENT, SUSCEPTIBILITY TO, 1; RPRGL1
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- OMIM
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<p>
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<span class="h4">#614389</span>
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<br />
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<strong>Table of Contents</strong>
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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/614389"><strong>Clinical Synopsis</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#pathogenesis">Pathogenesis</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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<div><a href="https://clinicaltrials.gov/search?cond=(PREGNANCY LOSS, RECURRENT) OR (F5)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/9210" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=614389[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>
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<span>
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<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.">
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<a id="title" class="mim-anchor"></a>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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614389
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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PREGNANCY LOSS, RECURRENT, SUSCEPTIBILITY TO, 1; RPRGL1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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<div>
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<h4>
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<span class="mim-font">
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RPRGL<br />
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RPL<br />
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ABORTION, SPONTANEOUS, RECURRENT<br />
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FETAL LOSS, RECURRENT, SUSCEPTIBILITY TO<br />
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MISCARRIAGE, RECURRENT<br />
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EMBRYONIC LOSS, RECURRENT<br />
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STILLBIRTH, RECURRENT
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</h4>
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</div>
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</div>
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<div>
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<br />
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<a id="phenotypeMap" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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Gene/Locus <br /> MIM number
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<span class="mim-font">
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<a href="/geneMap/1/1404?start=-3&limit=10&highlight=1404">
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1q24.2
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</a>
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<span class="mim-font">
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{Pregnancy loss, recurrent, susceptibility to, 1}
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<td>
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<span class="mim-font">
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<a href="/entry/614389"> 614389 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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F5
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/612309"> 612309 </a>
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</span>
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</td>
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</tbody>
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</table>
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<div>
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<div class="btn-group ">
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<a href="/clinicalSynopsis/614389" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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<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')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/614389" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/614389" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<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>
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<p />
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
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<div class="small" style="margin: 5px">
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<div>
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<span class="h5 mim-font">
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<strong> INHERITANCE </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br />
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> GENITOURINARY </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<em> Internal Genitalia (Female) </em>
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- Spontaneous abortion, recurrent <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3279439&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3279439</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0200067" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0200067</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0200067" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0200067</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/17369002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">17369002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/O03" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">O03</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/O03.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">O03.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/634" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">634</a>]</span><br /> -
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Fetal loss after 20 weeks or more of gestation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3280671&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3280671</a>]</span><br />
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<strong> MOLECULAR BASIS </strong>
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- Caused by mutation in the coagulation factor V gene (F5, <a href="/entry/612309#0001">612309.0001</a>)<br />
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that susceptibility to recurrent pregnancy loss-1 (RPRGL1) is conferred by variation in the coagulation factor V gene (F5; <a href="/entry/612309">612309</a>) on chromosome 1q24.</p>
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<p>Miscarriage, the commonest complication of pregnancy, is the spontaneous loss of a pregnancy before the fetus has reached viability. The term therefore includes all pregnancy losses from the time of conception until 24 weeks of gestation. Recurrent miscarriage, defined as 3 or more consecutive pregnancy losses, affects about 1% of couples; when defined as 2 or more losses, the scale of the problem increases to 5% of all couples trying to conceive (summary by <a href="#10" class="mim-tip-reference" title="Rai, R., Regan, L. <strong>Recurrent miscarriage.</strong> Lancet 368: 601-611, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16905025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16905025</a>] [<a href="https://doi.org/10.1016/S0140-6736(06)69204-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16905025">Rai and Regan, 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16905025" 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>Pregnancy losses have traditionally been designated 'spontaneous abortions' if they occur before 20 weeks gestation and 'stillbirths' if they occur after 20 weeks. Subtypes of spontaneous abortions can be further distinguished on the basis of embryonic development and include anembryonic loss in the first 5 weeks after conception (so-called 'blighted ovum'), embryonic loss from 6 to 9 weeks' gestation, and fetal loss from 10 weeks' gestation through the remainder of the pregnancy. These distinctions are important because the causes of pregnancy loss vary over gestational ages, with anembryonic losses being more likely to be associated with chromosomal abnormalities, for example. Possible etiologies for RPRGL include uterine anatomic abnormalities, cytogenetic abnormalities in the parents or fetus, single gene disorders, thrombophilic conditions, and immunologic or endocrine factors as well as environmental or infectious agents (summary by <a href="#13" class="mim-tip-reference" title="Warren, J. E., Silver, R. M. <strong>Genetics of pregnancy loss.</strong> Clin. Obstet. Gynec. 51: 84-95, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18303502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18303502</a>] [<a href="https://doi.org/10.1097/GRF.0b013e318161719c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18303502">Warren and Silver, 2008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18303502" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Genetic Heterogeneity of Recurrent Pregnancy Loss</em></strong></p><p>
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Susceptibility to RPRGL2 (<a href="/entry/614390">614390</a>) is conferred by mutation in the coagulation factor II gene (<a href="/entry/176930">176930</a>) on chromosome 11p11; RPRGL3 (<a href="/entry/614391">614391</a>) by mutation in the ANXA5 gene (<a href="/entry/131230">131230</a>) on chromosome 4q27; and RPRGL4 (see <a href="/entry/270960">270960</a>) by mutation in the SYCP3 gene (<a href="/entry/604759">604759</a>) on chromosome 12q23.</p><p>Genetic variation in the conceptus itself that results in decreased viability of the embryo or fetus is discussed in the respective gene and/or phenotype entry (see, e.g., MTHFR, <a href="/entry/607093#0004">607093.0004</a>; NLRP7, <a href="/entry/609661">609661</a>; hydatidiform mole, <a href="/entry/231090">231090</a>).</p>
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<strong>Pathogenesis</strong>
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<p><a href="#6" class="mim-tip-reference" title="Kwak-Kim, J., Yang, K. M., Gilman-Sachs, A. <strong>Recurrent pregnancy loss: a disease of inflammation and coagulation.</strong> J. Obstet. Gynaecol. Res. 35: 609-622, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19751318/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19751318</a>] [<a href="https://doi.org/10.1111/j.1447-0756.2009.01079.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19751318">Kwak-Kim et al. (2009)</a> noted that thrombotic/inflammatory processes are often observed at the maternal-fetal interface as the final pathologic insult in many cases of RPRGL. They reviewed the involvement of cellular immune responses and autoimmune abnormalities in women with RPRGL. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19751318" 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>Disorders of Coagulation</em></strong></p><p>
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Maternal hypercoagulability has been hypothesized to be a major causative factor in RPRGL (<a href="#1" class="mim-tip-reference" title="Allison, J. L., Schust, D. J. <strong>Recurrent first trimester pregnancy loss: revised definitions and novel causes.</strong> Curr. Opin. Endocr. Diabetes Obes. 16: 446-450, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19779333/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19779333</a>] [<a href="https://doi.org/10.1097/MED.0b013e3283327fc5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19779333">Allison and Schust, 2009</a>). See, e.g., antiphospholipid syndrome (<a href="/entry/107320">107320</a>), which involves arterial and venous thrombosis and recurrent fetal loss, and activated protein C resistance (<a href="/entry/188055">188055</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19779333" 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="Braulke, I., Hinney, G., Pruggmayer, M., Kostering, H., Melloh, P., Gunther, E. <strong>Factor XII (Hageman) deficiency in women with habitual abortion: new subpopulation of recurrent aborters?</strong> Fertil. Steril. 59: 98-101, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8419231/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8419231</a>] [<a href="https://doi.org/10.1016/s0015-0282(16)55622-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8419231">Braulke et al. (1993)</a> presented data suggesting that reduced levels of factor XII activity (<a href="/entry/234000">234000</a>) may be a risk factor for repeated spontaneous abortions. <a href="#12" class="mim-tip-reference" title="Standen, G. R., Bowen, D. J. <strong>Factor XIII A-Bristol 1: detection of a nonsense mutation (arg171-to-stop codon) in factor XIII A subunit deficiency.</strong> Brit. J. Haemat. 85: 769-772, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7918041/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7918041</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1993.tb03221.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7918041">Standen and Bowen (1993)</a> reported a woman with factor XIII deficiency (<a href="/entry/613225">613225</a>) who had 2 pregnancies terminate in spontaneous abortion, but 2 further pregnancies in which she was transfused with fresh frozen plasma resulted in live offspring. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7918041+8419231" 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>Pregnancy-Specific Glycoproteins</em></strong></p><p>
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Pregnancy-specific beta-1-glycoprotein (<a href="/entry/176390">176390</a>) levels have been found to correlate well with placental function and fetal well-being (<a href="#4" class="mim-tip-reference" title="Gordon, Y. B., Jeffrey, D., Grudzinska, J. G., Chard, T., Letchworth, A. T. <strong>Concentration of pregnancy-specific beta-1-glycoprotein in maternal blood in normal pregnancy and in intrauterine growth retardation.</strong> Lancet 309: 331-333, 1977. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/64859/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">64859</a>] [<a href="https://doi.org/10.1016/s0140-6736(77)91135-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="64859">Gordon et al., 1977</a>; <a href="#2" class="mim-tip-reference" title="Bartels, I., Lindemann, A. <strong>Maternal levels of pregnancy-specific beta-1-glycoprotein (SP-1) are elevated in pregnancies affected by Down's syndrome.</strong> Hum. Genet. 80: 46-48, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2971018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2971018</a>] [<a href="https://doi.org/10.1007/BF00451454" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2971018">Bartels and Lindemann, 1988</a>). Low pregnancy-specific glycoprotein (PSG) levels are associated with poor pregnancy outcome (<a href="#14" class="mim-tip-reference" title="Wurz, H., Geiger, W., Kunzig, H. J., Jabs-Lehmann, A., Bohn, H., Luben, G. <strong>Radioimmunoassay of SP1 (pregnancy-specific beta-1-glycoprotein) in maternal blood and in amniotic fluid in normal and pathologic pregnancies.</strong> J. Perinat. Med. 9: 67-78, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6787188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6787188</a>] [<a href="https://doi.org/10.1515/jpme.1981.9.2.67" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6787188">Wurz et al., 1981</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2971018+64859+6787188" 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>Trophoblast-Lymphocyte Crossreactive Alloantigens</em></strong></p><p>
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<a href="#9" class="mim-tip-reference" title="McIntyre, J. A., Faulk, W. P., Verhulst, S. J., Colliver, J. A. <strong>Human trophoblast-lymphocyte cross-reactive (TLX) antigens define a new alloantigen system.</strong> Science 222: 1135-1137, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6648525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6648525</a>] [<a href="https://doi.org/10.1126/science.6648525" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6648525">McIntyre et al. (1983)</a> proposed that trophoblast-lymphocyte crossreactive alloantigens (TLX; <a href="/entry/120920">120920</a>) are central in establishing maternal recognition and protection of the blastocyst, and that lack of recognition results in implantation failure and spontaneous abortion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6648525" 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>P-Related IgG and IgM Antibodies</em></strong></p><p>
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<a href="#5" class="mim-tip-reference" title="Hellberg, A., Ringressi, A., Yahalom, V., Safwenberg, J., Reid, M. E., Olsson, M. L. <strong>Genetic heterogeneity at the glycosyltransferase loci underlying the GLOB blood group system and collection.</strong> Brit. J. Haemat. 125: 528-536, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15142124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15142124</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2004.04930.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15142124">Hellberg et al. (2004)</a> explored the molecular basis of the clinically important but rare blood group phenotypes p, P1(k), and P2(k), by analysis of the A4GALT (<a href="/entry/607922">607922</a>) and B3GALT3 (<a href="/entry/603094">603094</a>) genes, which are responsible for synthesis of the related Gb3 and Gb4 antigens, respectively. Lack of these glycolipid moieties is associated with severe transfusion reactions and recurrent spontaneous abortions but also offers immunity against infectious agents. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15142124" 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>Other Related Factors</em></strong></p><p>
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<a href="#11" class="mim-tip-reference" title="Salker, M. S., Christian, M., Steel, J. H., Nautiyal, J., Lavery, S., Trew, G., Webster, Z., Al-Sabbagh, M., Puchchakayala, G., Foller, M., Landles, C., Sharkey, A. M., Quenby, S., Aplin, J. D., Regan, L., Lang, F., Brosens, J. J. <strong>Deregulation of the serum- and glucocorticoid-inducible kinase SGK1 in the endometrium causes reproductive failure.</strong> Nature Med. 17: 1509-1513, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22001908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22001908</a>] [<a href="https://doi.org/10.1038/nm.2498" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22001908">Salker et al. (2011)</a> observed that SGK1 (<a href="/entry/602958">602958</a>), a kinase involved in epithelial ion transport and cell survival, was downregulated in midsecretory endometrial samples from women with RPRGL, whereas SGK1 was upregulated in samples from patients with unexplained infertility. Relative SGK1 deficiency was also a hallmark of decidualizing stromal cells from women with RPRGL, sensitizing those cells to oxidative cell death and rendering the fetomaternal interface vulnerable to oxidative damage. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22001908" 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="#7" class="mim-tip-reference" title="Majerus, P. W. <strong>Bad blood by mutation.</strong> Nature 369: 14-15, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8164730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8164730</a>] [<a href="https://doi.org/10.1038/369014a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8164730">Majerus (1994)</a> noted that an estimated 2 to 4% of the Dutch population and 7% of the Swedish population carried a mutant R506Q allele of coagulation factor V, the 'factor V Leiden' variant (<a href="/entry/612309#0001">612309.0001</a>). The high frequency of a single factor V mutation in diverse groups of people raised the question of whether positive selection pressure was involved in maintaining it in the population. <a href="#7" class="mim-tip-reference" title="Majerus, P. W. <strong>Bad blood by mutation.</strong> Nature 369: 14-15, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8164730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8164730</a>] [<a href="https://doi.org/10.1038/369014a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8164730">Majerus (1994)</a> suggested that a slight thrombotic tendency may confer some advantage in fetal implantation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8164730" 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 67 women with a first episode of unexplained late fetal loss (fetal death after 20 weeks or more of gestation) and 232 women who had had 1 or more normal pregnancies with no late fetal loss, <a href="#8" class="mim-tip-reference" title="Martinelli, I., Taioli, E., Cetin, I., Marinoni, A., Gerosa, S., Villa, M. V., Bozzo, M., Mannucci, P. M. <strong>Mutations in coagulation factors in women with unexplained late fetal loss.</strong> New Eng. J. Med. 343: 1015-1018, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11018168/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11018168</a>] [<a href="https://doi.org/10.1056/NEJM200010053431405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11018168">Martinelli et al. (2000)</a> found that both factor V Leiden and a 20210G-A mutation in prothrombin (<a href="/entry/176930#0009">176930.0009</a>) were associated with an approximate tripling of the risk of late fetal loss. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11018168" 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>Associations Pending Confirmation</em></strong></p><p>
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Associations between certain HLA polymorphisms and RPRGL have been reported; see, e.g., HLA-G (<a href="/entry/142871">142871</a>), HLA-DRB1 (<a href="/entry/142857">142857</a>), and HLA-DQB1 (<a href="/entry/604305">604305</a>).</p><p>For discussion of a possible association between RPRGL and variation in the NOS3 gene, see <a href="/entry/163729">163729</a>.</p><p>For discussion of a possible association between RPRGL and variation in the JAK2 gene, see <a href="/entry/147796">147796</a>.</p><p>For discussion of a possible association between RPRGL and variation in the NLRP7 gene, see <a href="/entry/609661">609661</a>.</p>
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<ol>
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<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Allison2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Allison, J. L., Schust, D. J.
|
|
<strong>Recurrent first trimester pregnancy loss: revised definitions and novel causes.</strong>
|
|
Curr. Opin. Endocr. Diabetes Obes. 16: 446-450, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19779333/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19779333</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19779333" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
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[<a href="https://doi.org/10.1097/MED.0b013e3283327fc5" target="_blank">Full Text</a>]
|
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|
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|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Bartels1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bartels, I., Lindemann, A.
|
|
<strong>Maternal levels of pregnancy-specific beta-1-glycoprotein (SP-1) are elevated in pregnancies affected by Down's syndrome.</strong>
|
|
Hum. Genet. 80: 46-48, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2971018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2971018</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2971018" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
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|
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[<a href="https://doi.org/10.1007/BF00451454" target="_blank">Full Text</a>]
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Braulke1993" class="mim-anchor"></a>
|
|
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|
|
<p class="mim-text-font">
|
|
Braulke, I., Hinney, G., Pruggmayer, M., Kostering, H., Melloh, P., Gunther, E.
|
|
<strong>Factor XII (Hageman) deficiency in women with habitual abortion: new subpopulation of recurrent aborters?</strong>
|
|
Fertil. Steril. 59: 98-101, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8419231/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8419231</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8419231" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1016/s0015-0282(16)55622-2" target="_blank">Full Text</a>]
|
|
|
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|
|
</p>
|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Gordon1977" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gordon, Y. B., Jeffrey, D., Grudzinska, J. G., Chard, T., Letchworth, A. T.
|
|
<strong>Concentration of pregnancy-specific beta-1-glycoprotein in maternal blood in normal pregnancy and in intrauterine growth retardation.</strong>
|
|
Lancet 309: 331-333, 1977. Note: Originally Volume I.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/64859/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">64859</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=64859" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1016/s0140-6736(77)91135-7" target="_blank">Full Text</a>]
|
|
|
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|
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</p>
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
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|
|
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|
|
<p class="mim-text-font">
|
|
Hellberg, A., Ringressi, A., Yahalom, V., Safwenberg, J., Reid, M. E., Olsson, M. L.
|
|
<strong>Genetic heterogeneity at the glycosyltransferase loci underlying the GLOB blood group system and collection.</strong>
|
|
Brit. J. Haemat. 125: 528-536, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15142124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15142124</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15142124" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.2004.04930.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
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|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kwak-Kim, J., Yang, K. M., Gilman-Sachs, A.
|
|
<strong>Recurrent pregnancy loss: a disease of inflammation and coagulation.</strong>
|
|
J. Obstet. Gynaecol. Res. 35: 609-622, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19751318/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19751318</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19751318" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1447-0756.2009.01079.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
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<a id="Majerus1994" class="mim-anchor"></a>
|
|
<div class="">
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|
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|
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Majerus, P. W.
|
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<strong>Bad blood by mutation.</strong>
|
|
Nature 369: 14-15, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8164730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8164730</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8164730" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1038/369014a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
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</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
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<a id="Martinelli2000" class="mim-anchor"></a>
|
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|
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|
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Martinelli, I., Taioli, E., Cetin, I., Marinoni, A., Gerosa, S., Villa, M. V., Bozzo, M., Mannucci, P. M.
|
|
<strong>Mutations in coagulation factors in women with unexplained late fetal loss.</strong>
|
|
New Eng. J. Med. 343: 1015-1018, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11018168/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11018168</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11018168" 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/NEJM200010053431405" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="McIntyre1983" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McIntyre, J. A., Faulk, W. P., Verhulst, S. J., Colliver, J. A.
|
|
<strong>Human trophoblast-lymphocyte cross-reactive (TLX) antigens define a new alloantigen system.</strong>
|
|
Science 222: 1135-1137, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6648525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6648525</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6648525" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
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|
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[<a href="https://doi.org/10.1126/science.6648525" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
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|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rai, R., Regan, L.
|
|
<strong>Recurrent miscarriage.</strong>
|
|
Lancet 368: 601-611, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16905025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16905025</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16905025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/S0140-6736(06)69204-0" target="_blank">Full Text</a>]
|
|
|
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|
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|
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|
|
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|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
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|
|
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|
|
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|
|
Salker, M. S., Christian, M., Steel, J. H., Nautiyal, J., Lavery, S., Trew, G., Webster, Z., Al-Sabbagh, M., Puchchakayala, G., Foller, M., Landles, C., Sharkey, A. M., Quenby, S., Aplin, J. D., Regan, L., Lang, F., Brosens, J. J.
|
|
<strong>Deregulation of the serum- and glucocorticoid-inducible kinase SGK1 in the endometrium causes reproductive failure.</strong>
|
|
Nature Med. 17: 1509-1513, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22001908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22001908</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22001908" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nm.2498" target="_blank">Full Text</a>]
|
|
|
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|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
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<a id="Standen1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Standen, G. R., Bowen, D. J.
|
|
<strong>Factor XIII A-Bristol 1: detection of a nonsense mutation (arg171-to-stop codon) in factor XIII A subunit deficiency.</strong>
|
|
Brit. J. Haemat. 85: 769-772, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7918041/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7918041</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7918041" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
|
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[<a href="https://doi.org/10.1111/j.1365-2141.1993.tb03221.x" target="_blank">Full Text</a>]
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|
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<li>
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<a id="Warren2008" class="mim-anchor"></a>
|
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|
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|
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Warren, J. E., Silver, R. M.
|
|
<strong>Genetics of pregnancy loss.</strong>
|
|
Clin. Obstet. Gynec. 51: 84-95, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18303502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18303502</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18303502" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1097/GRF.0b013e318161719c" target="_blank">Full Text</a>]
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<li>
|
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|
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|
|
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|
|
Wurz, H., Geiger, W., Kunzig, H. J., Jabs-Lehmann, A., Bohn, H., Luben, G.
|
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<strong>Radioimmunoassay of SP1 (pregnancy-specific beta-1-glycoprotein) in maternal blood and in amniotic fluid in normal and pathologic pregnancies.</strong>
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J. Perinat. Med. 9: 67-78, 1981.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6787188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6787188</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6787188" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1515/jpme.1981.9.2.67" target="_blank">Full Text</a>]
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Marla J. F. O'Neill - updated : 2/26/2016
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Marla J. F. O'Neill - updated : 12/15/2011
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Marla J. F. O'Neill : 12/12/2011
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alopez : 03/20/2023
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carol : 05/12/2016<br>carol : 5/12/2016<br>carol : 5/12/2016<br>carol : 2/29/2016<br>carol : 2/26/2016<br>alopez : 1/28/2015<br>terry : 5/22/2012<br>terry : 5/7/2012<br>terry : 12/15/2011<br>alopez : 12/13/2011
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<span class="mim-font">
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<strong>#</strong> 614389
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<h3>
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PREGNANCY LOSS, RECURRENT, SUSCEPTIBILITY TO, 1; RPRGL1
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<em>Alternative titles; symbols</em>
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<span class="mim-font">
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RPRGL<br />
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RPL<br />
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ABORTION, SPONTANEOUS, RECURRENT<br />
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FETAL LOSS, RECURRENT, SUSCEPTIBILITY TO<br />
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MISCARRIAGE, RECURRENT<br />
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EMBRYONIC LOSS, RECURRENT<br />
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STILLBIRTH, RECURRENT
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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</th>
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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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<span class="mim-font">
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1q24.2
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<span class="mim-font">
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{Pregnancy loss, recurrent, susceptibility to, 1}
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<span class="mim-font">
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614389
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<span class="mim-font">
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Autosomal dominant
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<span class="mim-font">
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3
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F5
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612309
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<strong>TEXT</strong>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because of evidence that susceptibility to recurrent pregnancy loss-1 (RPRGL1) is conferred by variation in the coagulation factor V gene (F5; 612309) on chromosome 1q24.</p>
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<span class="mim-font">
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<strong>Description</strong>
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<p>Miscarriage, the commonest complication of pregnancy, is the spontaneous loss of a pregnancy before the fetus has reached viability. The term therefore includes all pregnancy losses from the time of conception until 24 weeks of gestation. Recurrent miscarriage, defined as 3 or more consecutive pregnancy losses, affects about 1% of couples; when defined as 2 or more losses, the scale of the problem increases to 5% of all couples trying to conceive (summary by Rai and Regan, 2006). </p><p>Pregnancy losses have traditionally been designated 'spontaneous abortions' if they occur before 20 weeks gestation and 'stillbirths' if they occur after 20 weeks. Subtypes of spontaneous abortions can be further distinguished on the basis of embryonic development and include anembryonic loss in the first 5 weeks after conception (so-called 'blighted ovum'), embryonic loss from 6 to 9 weeks' gestation, and fetal loss from 10 weeks' gestation through the remainder of the pregnancy. These distinctions are important because the causes of pregnancy loss vary over gestational ages, with anembryonic losses being more likely to be associated with chromosomal abnormalities, for example. Possible etiologies for RPRGL include uterine anatomic abnormalities, cytogenetic abnormalities in the parents or fetus, single gene disorders, thrombophilic conditions, and immunologic or endocrine factors as well as environmental or infectious agents (summary by Warren and Silver, 2008). </p><p><strong><em>Genetic Heterogeneity of Recurrent Pregnancy Loss</em></strong></p><p>
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Susceptibility to RPRGL2 (614390) is conferred by mutation in the coagulation factor II gene (176930) on chromosome 11p11; RPRGL3 (614391) by mutation in the ANXA5 gene (131230) on chromosome 4q27; and RPRGL4 (see 270960) by mutation in the SYCP3 gene (604759) on chromosome 12q23.</p><p>Genetic variation in the conceptus itself that results in decreased viability of the embryo or fetus is discussed in the respective gene and/or phenotype entry (see, e.g., MTHFR, 607093.0004; NLRP7, 609661; hydatidiform mole, 231090).</p>
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<h4>
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<span class="mim-font">
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<strong>Pathogenesis</strong>
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<span class="mim-text-font">
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<p>Kwak-Kim et al. (2009) noted that thrombotic/inflammatory processes are often observed at the maternal-fetal interface as the final pathologic insult in many cases of RPRGL. They reviewed the involvement of cellular immune responses and autoimmune abnormalities in women with RPRGL. </p><p><strong><em>Disorders of Coagulation</em></strong></p><p>
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Maternal hypercoagulability has been hypothesized to be a major causative factor in RPRGL (Allison and Schust, 2009). See, e.g., antiphospholipid syndrome (107320), which involves arterial and venous thrombosis and recurrent fetal loss, and activated protein C resistance (188055). </p><p>Braulke et al. (1993) presented data suggesting that reduced levels of factor XII activity (234000) may be a risk factor for repeated spontaneous abortions. Standen and Bowen (1993) reported a woman with factor XIII deficiency (613225) who had 2 pregnancies terminate in spontaneous abortion, but 2 further pregnancies in which she was transfused with fresh frozen plasma resulted in live offspring. </p><p><strong><em>Pregnancy-Specific Glycoproteins</em></strong></p><p>
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Pregnancy-specific beta-1-glycoprotein (176390) levels have been found to correlate well with placental function and fetal well-being (Gordon et al., 1977; Bartels and Lindemann, 1988). Low pregnancy-specific glycoprotein (PSG) levels are associated with poor pregnancy outcome (Wurz et al., 1981). </p><p><strong><em>Trophoblast-Lymphocyte Crossreactive Alloantigens</em></strong></p><p>
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McIntyre et al. (1983) proposed that trophoblast-lymphocyte crossreactive alloantigens (TLX; 120920) are central in establishing maternal recognition and protection of the blastocyst, and that lack of recognition results in implantation failure and spontaneous abortion. </p><p><strong><em>P-Related IgG and IgM Antibodies</em></strong></p><p>
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Hellberg et al. (2004) explored the molecular basis of the clinically important but rare blood group phenotypes p, P1(k), and P2(k), by analysis of the A4GALT (607922) and B3GALT3 (603094) genes, which are responsible for synthesis of the related Gb3 and Gb4 antigens, respectively. Lack of these glycolipid moieties is associated with severe transfusion reactions and recurrent spontaneous abortions but also offers immunity against infectious agents. </p><p><strong><em>Other Related Factors</em></strong></p><p>
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Salker et al. (2011) observed that SGK1 (602958), a kinase involved in epithelial ion transport and cell survival, was downregulated in midsecretory endometrial samples from women with RPRGL, whereas SGK1 was upregulated in samples from patients with unexplained infertility. Relative SGK1 deficiency was also a hallmark of decidualizing stromal cells from women with RPRGL, sensitizing those cells to oxidative cell death and rendering the fetomaternal interface vulnerable to oxidative damage. </p>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</h4>
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<span class="mim-text-font">
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<p>Majerus (1994) noted that an estimated 2 to 4% of the Dutch population and 7% of the Swedish population carried a mutant R506Q allele of coagulation factor V, the 'factor V Leiden' variant (612309.0001). The high frequency of a single factor V mutation in diverse groups of people raised the question of whether positive selection pressure was involved in maintaining it in the population. Majerus (1994) suggested that a slight thrombotic tendency may confer some advantage in fetal implantation. </p><p>In a study of 67 women with a first episode of unexplained late fetal loss (fetal death after 20 weeks or more of gestation) and 232 women who had had 1 or more normal pregnancies with no late fetal loss, Martinelli et al. (2000) found that both factor V Leiden and a 20210G-A mutation in prothrombin (176930.0009) were associated with an approximate tripling of the risk of late fetal loss. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
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Associations between certain HLA polymorphisms and RPRGL have been reported; see, e.g., HLA-G (142871), HLA-DRB1 (142857), and HLA-DQB1 (604305).</p><p>For discussion of a possible association between RPRGL and variation in the NOS3 gene, see 163729.</p><p>For discussion of a possible association between RPRGL and variation in the JAK2 gene, see 147796.</p><p>For discussion of a possible association between RPRGL and variation in the NLRP7 gene, see 609661.</p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<ol>
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<li>
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<p class="mim-text-font">
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Allison, J. L., Schust, D. J.
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<strong>Recurrent first trimester pregnancy loss: revised definitions and novel causes.</strong>
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Curr. Opin. Endocr. Diabetes Obes. 16: 446-450, 2009.
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[PubMed: 19779333]
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[Full Text: https://doi.org/10.1097/MED.0b013e3283327fc5]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Bartels, I., Lindemann, A.
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<strong>Maternal levels of pregnancy-specific beta-1-glycoprotein (SP-1) are elevated in pregnancies affected by Down's syndrome.</strong>
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Hum. Genet. 80: 46-48, 1988.
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[PubMed: 2971018]
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[Full Text: https://doi.org/10.1007/BF00451454]
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</p>
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<li>
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<p class="mim-text-font">
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Braulke, I., Hinney, G., Pruggmayer, M., Kostering, H., Melloh, P., Gunther, E.
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<strong>Factor XII (Hageman) deficiency in women with habitual abortion: new subpopulation of recurrent aborters?</strong>
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Fertil. Steril. 59: 98-101, 1993.
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[PubMed: 8419231]
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[Full Text: https://doi.org/10.1016/s0015-0282(16)55622-2]
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</li>
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<li>
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<p class="mim-text-font">
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Gordon, Y. B., Jeffrey, D., Grudzinska, J. G., Chard, T., Letchworth, A. T.
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<strong>Concentration of pregnancy-specific beta-1-glycoprotein in maternal blood in normal pregnancy and in intrauterine growth retardation.</strong>
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Lancet 309: 331-333, 1977. Note: Originally Volume I.
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[PubMed: 64859]
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[Full Text: https://doi.org/10.1016/s0140-6736(77)91135-7]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Hellberg, A., Ringressi, A., Yahalom, V., Safwenberg, J., Reid, M. E., Olsson, M. L.
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<strong>Genetic heterogeneity at the glycosyltransferase loci underlying the GLOB blood group system and collection.</strong>
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Brit. J. Haemat. 125: 528-536, 2004.
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[PubMed: 15142124]
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[Full Text: https://doi.org/10.1111/j.1365-2141.2004.04930.x]
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</li>
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<li>
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<p class="mim-text-font">
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Kwak-Kim, J., Yang, K. M., Gilman-Sachs, A.
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<strong>Recurrent pregnancy loss: a disease of inflammation and coagulation.</strong>
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J. Obstet. Gynaecol. Res. 35: 609-622, 2009.
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[PubMed: 19751318]
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[Full Text: https://doi.org/10.1111/j.1447-0756.2009.01079.x]
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</li>
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<li>
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<p class="mim-text-font">
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Majerus, P. W.
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<strong>Bad blood by mutation.</strong>
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Nature 369: 14-15, 1994.
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[PubMed: 8164730]
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[Full Text: https://doi.org/10.1038/369014a0]
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</li>
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<li>
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<p class="mim-text-font">
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Martinelli, I., Taioli, E., Cetin, I., Marinoni, A., Gerosa, S., Villa, M. V., Bozzo, M., Mannucci, P. M.
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<strong>Mutations in coagulation factors in women with unexplained late fetal loss.</strong>
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New Eng. J. Med. 343: 1015-1018, 2000.
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[PubMed: 11018168]
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[Full Text: https://doi.org/10.1056/NEJM200010053431405]
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|
<li>
|
|
<p class="mim-text-font">
|
|
McIntyre, J. A., Faulk, W. P., Verhulst, S. J., Colliver, J. A.
|
|
<strong>Human trophoblast-lymphocyte cross-reactive (TLX) antigens define a new alloantigen system.</strong>
|
|
Science 222: 1135-1137, 1983.
|
|
|
|
|
|
[PubMed: 6648525]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.6648525]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rai, R., Regan, L.
|
|
<strong>Recurrent miscarriage.</strong>
|
|
Lancet 368: 601-611, 2006.
|
|
|
|
|
|
[PubMed: 16905025]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/S0140-6736(06)69204-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Salker, M. S., Christian, M., Steel, J. H., Nautiyal, J., Lavery, S., Trew, G., Webster, Z., Al-Sabbagh, M., Puchchakayala, G., Foller, M., Landles, C., Sharkey, A. M., Quenby, S., Aplin, J. D., Regan, L., Lang, F., Brosens, J. J.
|
|
<strong>Deregulation of the serum- and glucocorticoid-inducible kinase SGK1 in the endometrium causes reproductive failure.</strong>
|
|
Nature Med. 17: 1509-1513, 2011.
|
|
|
|
|
|
[PubMed: 22001908]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nm.2498]
|
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|
|
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Standen, G. R., Bowen, D. J.
|
|
<strong>Factor XIII A-Bristol 1: detection of a nonsense mutation (arg171-to-stop codon) in factor XIII A subunit deficiency.</strong>
|
|
Brit. J. Haemat. 85: 769-772, 1993.
|
|
|
|
|
|
[PubMed: 7918041]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1993.tb03221.x]
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Warren, J. E., Silver, R. M.
|
|
<strong>Genetics of pregnancy loss.</strong>
|
|
Clin. Obstet. Gynec. 51: 84-95, 2008.
|
|
|
|
|
|
[PubMed: 18303502]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/GRF.0b013e318161719c]
|
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</p>
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</li>
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Wurz, H., Geiger, W., Kunzig, H. J., Jabs-Lehmann, A., Bohn, H., Luben, G.
|
|
<strong>Radioimmunoassay of SP1 (pregnancy-specific beta-1-glycoprotein) in maternal blood and in amniotic fluid in normal and pathologic pregnancies.</strong>
|
|
J. Perinat. Med. 9: 67-78, 1981.
|
|
|
|
|
|
[PubMed: 6787188]
|
|
|
|
|
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[Full Text: https://doi.org/10.1515/jpme.1981.9.2.67]
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Marla J. F. O'Neill - updated : 2/26/2016<br>Marla J. F. O'Neill - updated : 12/15/2011
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