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<title>
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Entry
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- #616214 - HYPERPROINSULINEMIA
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- OMIM
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<span class="h4">#616214</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/616214"><strong>Clinical Synopsis</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=(HYPERPROINSULINEMIA) OR (INS)" 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.ncbi.nlm.nih.gov/gtr/all/tests/?term=616214[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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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 237613005<br />
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">ICD+</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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616214
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</span>
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</span>
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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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HYPERPROINSULINEMIA
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</span>
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</h3>
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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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</th>
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<th>
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Gene/Locus <br /> MIM number
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td>
|
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<span class="mim-font">
|
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<a href="/geneMap/11/74?start=-3&limit=10&highlight=74">
|
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11p15.5
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</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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Hyperproinsulinemia
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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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<a href="/entry/616214"> 616214 </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>
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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="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</td>
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<td>
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<span class="mim-font">
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INS
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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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<a href="/entry/176730"> 176730 </a>
|
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</span>
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</td>
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</tr>
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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/616214" 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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<div class="btn-group">
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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/616214" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
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<li><a href="/graph/radial/616214" 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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<div>
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<p />
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</div>
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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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<span class="h5 mim-font">
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<strong> INHERITANCE </strong>
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</span>
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<div style="margin-left: 2em;">
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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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<span class="h5 mim-font">
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<strong> ENDOCRINE FEATURES </strong>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Hyperproinsulinemia (asymptomatic in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237613005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237613005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0342283&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0342283</a>]</span><br /> -
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Hyperinsulinemia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/131103005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">131103005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/83469008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">83469008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E16.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E16.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0852795&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0852795</a>, <a href="https://bioportal.bioontology.org/search?q=C0020459&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020459</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000842" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000842</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000842" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000842</a>]</span><br /> -
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Hyperglycemia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/444780001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">444780001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237598005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237598005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80394007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80394007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R73.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R73.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2919432&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2919432</a>, <a href="https://bioportal.bioontology.org/search?q=C0020456&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020456</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003074" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003074</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003074" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003074</a>]</span><br /> -
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Normal response to exogenously administered insulin <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4015535&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4015535</a>]</span><br />
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</span>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MOLECULAR BASIS </strong>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Caused by mutation in the insulin gene (INS, <a href="/entry/176730#0001">176730.0001</a>)<br />
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</span>
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<div class="text-right">
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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</div>
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<div>
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<br />
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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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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</span>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because hyperproinsulinemia is caused by heterozygous mutation in the INS gene (<a href="/entry/176730">176730</a>) on chromosome 11p15.</p>
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<a id="description" class="mim-anchor"></a>
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Description</strong>
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</h4>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>Insulin (INS; <a href="/entry/176730">176730</a>) is produced posttranslationally from its precursor molecule, proinsulin, by site-directed proteolysis in beta-cell granules. Conversion involves cleavage at pairs of basic residues that link both the insulin A and B chains to C-peptide. Human proinsulin conversion has a preferred sequential route, such that cleavage at the B-chain/C-peptide junction occurs first, producing des-31,32 split proinsulin as the major conversion intermediate. Under normal circumstances, proinsulin conversion is largely completed before secretion, and low plasma levels of intact proinsulin and conversion intermediates are found. Structural abnormalities in the proinsulin molecule can impair conversion, leading to the accumulation of proinsulin-like material in the circulation. Such defects show an autosomal dominant mode of inheritance and are the main cause of familial hyperproinsulinemia (summary by <a href="#16" class="mim-tip-reference" title="Warren-Perry, M. G., Manley, S. E., Ostrega, D., Polonsky, K., Mussett, S., Brown, P., Turner, R. C. <strong>A novel point mutation in the insulin gene giving rise to hyperproinsulinemia.</strong> J. Clin. Endocr. Metab. 82: 1629-1631, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9141561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9141561</a>] [<a href="https://doi.org/10.1210/jcem.82.5.3914" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9141561">Warren-Perry et al., 1997</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9141561" 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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<br />
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<a id="clinicalFeatures" class="mim-anchor"></a>
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<strong>Clinical Features</strong>
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<p><a href="#4" class="mim-tip-reference" title="Gabbay, K. H., DeLuca, K., Fisher, J. N., Jr., Mako, M. E., Rubenstein, A. H. <strong>Familial hyperproinsulinemia: an autosomal dominant defect.</strong> New Eng. J. Med. 294: 911-915, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/815812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">815812</a>] [<a href="https://doi.org/10.1056/NEJM197604222941701" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="815812">Gabbay et al. (1976)</a> described a family in which many persons in an autosomal dominant pattern had proinsulin or a proinsulin-like material as the major fraction of circulating insulin immunoreactivity in both the fasting and the stimulated state. The hyperproinsulinemia was asymptomatic, with no evident relation to hypoglycemia or development of diabetes mellitus. In light of the dominant inheritance, the authors thought a structural abnormality of proinsulin to be more likely than deficiency of the proinsulin cleaving enzyme (or enzymes). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=815812" 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="Gabbay, K. H., Bergenstal, R. M., Wolff, J., Mako, M. E., Rubenstein, A. H. <strong>Familial hyperproinsulinemia: partial characterization of circulating proinsulin-like material.</strong> Proc. Nat. Acad. Sci. 76: 2881-2885, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/288074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">288074</a>] [<a href="https://doi.org/10.1073/pnas.76.6.2881" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="288074">Gabbay et al. (1979)</a> presented data indicating that proinsulin in familial hyperproinsulinemia indeed has a structural abnormality such that cleavage at the B chain/C peptide site is impaired. <a href="#9" class="mim-tip-reference" title="Kanazawa, Y., Hayashi, M., Ikeuchi, M., Hiramatsu, K., Kosaka, K. <strong>Familial proinsulinemia: a possible cause of abnormal glucose tolerance. (Abstract)</strong> Europ. J. Clin. Invest. 8: 327, 1978."None>Kanazawa et al. (1978)</a> described the counterpart of the defect reported by Gabbay et al. (<a href="#4" class="mim-tip-reference" title="Gabbay, K. H., DeLuca, K., Fisher, J. N., Jr., Mako, M. E., Rubenstein, A. H. <strong>Familial hyperproinsulinemia: an autosomal dominant defect.</strong> New Eng. J. Med. 294: 911-915, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/815812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">815812</a>] [<a href="https://doi.org/10.1056/NEJM197604222941701" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="815812">1976</a>, <a href="#3" class="mim-tip-reference" title="Gabbay, K. H., Bergenstal, R. M., Wolff, J., Mako, M. E., Rubenstein, A. H. <strong>Familial hyperproinsulinemia: partial characterization of circulating proinsulin-like material.</strong> Proc. Nat. Acad. Sci. 76: 2881-2885, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/288074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">288074</a>] [<a href="https://doi.org/10.1073/pnas.76.6.2881" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="288074">1979</a>): hyperproinsulinemia due to mutation at the cleavage site connecting the A chain to the C peptide. Inheritance was again autosomal dominant. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=815812+288074" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Shoelson, S., Haneda, M., Blix, P., Nanjo, A., Sanke, T., Inouye, K., Steiner, D., Rubenstein, A., Tager, H. <strong>Three mutant insulins in man.</strong> Nature 302: 540-543, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6339950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6339950</a>] [<a href="https://doi.org/10.1038/302540a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6339950">Shoelson et al. (1983)</a> studied 3 unrelated patients, 1 of whom was previously reported by <a href="#14" class="mim-tip-reference" title="Tager, H., Given, B., Baldwin, D., Mako, M., Markese, J., Rubenstein, A., Olefsky, J., Kobayashi, M., Kolterman, O., Poucher, R. <strong>A structurally abnormal insulin causing human diabetes.</strong> Nature 281: 122-125, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/381941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">381941</a>] [<a href="https://doi.org/10.1038/281122a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="381941">Tager et al. (1979)</a> and 1 of whom was previously reported by <a href="#12" class="mim-tip-reference" title="Shoelson, S., Fickova, M., Haneda, M., Nahum, A., Musso, G., Kaiser, E. T., Rubenstein, A. H., Tager, H. <strong>Identification of a mutant human insulin predicted to contain a serine-for-phenylalanine substitution.</strong> Proc. Nat. Acad. Sci. 80: 7390-7394, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6424111/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6424111</a>] [<a href="https://doi.org/10.1073/pnas.80.24.7390" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6424111">Shoelson et al. (1983)</a>, with diabetes-type hyperglycemia and marked hyperinsulinemia suggestive of insulin resistance but with normal response to exogenously administered insulin. Because the opportunity to study pancreatic tissue was rare, the authors developed a method combining high pressure liquid chromatography and radioimmunoassay. By this method, each of the 3 patients was found to secrete a structurally variant and chemically distinct insulin. All 3 patients were heterozygous. Two patients came from families in which many members of several generations had the variant insulin in an autosomal dominant pedigree pattern and had either normal or very mildly impaired glucose tolerance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6424111+381941+6339950" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Gruppuso, P. A., Gorden, P., Kahn, C. R., Cornblath, M., Zeller, W. P., Schwartz, R. <strong>Familial hyperproinsulinemia due to a proposed defect in conversion of proinsulin to insulin.</strong> New Eng. J. Med. 311: 629-634, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6382002/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6382002</a>] [<a href="https://doi.org/10.1056/NEJM198409063111003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6382002">Gruppuso et al. (1984)</a> identified a hyperproinsulinemia kindred in which the proband, a 14-year-old girl with a history of transient hyperglycemia at age 2 years, was studied for symptoms of hypoglycemia. Elevated levels of proinsulin were found in her and 2 sibs, her father, and her paternal grandfather, whereas 4 other close relatives were normal. <a href="#6" class="mim-tip-reference" title="Gruppuso, P. A., Gorden, P., Kahn, C. R., Cornblath, M., Zeller, W. P., Schwartz, R. <strong>Familial hyperproinsulinemia due to a proposed defect in conversion of proinsulin to insulin.</strong> New Eng. J. Med. 311: 629-634, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6382002/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6382002</a>] [<a href="https://doi.org/10.1056/NEJM198409063111003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6382002">Gruppuso et al. (1984)</a> suggested that hyperproinsulinemia present in 5 persons in 3 consecutive generations with male-to-male transmission was due not to a structural defect of the proinsulin molecule but to a defect in the conversion mechanism in the pancreas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6382002" 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 4 persons in 2 generations, <a href="#15" class="mim-tip-reference" title="Vinik, A. I., Seino, S., Funakoshi, A., Schwartz, J., Matsumoto, M., Schteingart, D. E., Fu, Z.-Z., Tsai, S.-T. <strong>Familial hyperinsulinemia associated with secretion of an abnormal insulin, and coexistence of insulin resistance in the propositus.</strong> J. Clin. Endocr. Metab. 62: 645-652, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3512591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3512591</a>] [<a href="https://doi.org/10.1210/jcem-62-4-645" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3512591">Vinik et al. (1986)</a> described a structural defect of insulin associated with hyperinsulinemia. The insulin was found to elute later than normal human insulin on reverse phase high performance liquid chromatography. It was more hydrophobic than normal human insulin and had only 10% of the activity of normal insulin in terms of ability to bind to isolated rat adipocytes and stimulate glucose metabolism in them. The proband, aged 45 years, had a 9-year history of syncopal attacks. He showed resistance to exogenous insulin. Plasma counterregulatory hormones (glucagon, growth hormone, cortisol, epinephrine, norepinephrine) showed normal concentrations. Binding of exogenous insulin by the patient's cells was normal. The abnormal insulin was demonstrated in 2 of 3 sons and in a sister but not in the mother, brother, or niece. Sensitivity to insulin was normal in the 2 sons who had abnormal insulin. The explanation for the insulin resistance in the proband was unclear. The authors thought that the change in the insulin molecule in this family was different from either the B24 phe-to-ser (<a href="/entry/176730#0002">176730.0002</a>) or the B25 phe-to-leu (<a href="/entry/176730#0001">176730.0001</a>) mutations previously described. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3512591" 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>The transmission pattern of hyperproinsulinemia in the families reported by <a href="#13" class="mim-tip-reference" title="Shoelson, S., Haneda, M., Blix, P., Nanjo, A., Sanke, T., Inouye, K., Steiner, D., Rubenstein, A., Tager, H. <strong>Three mutant insulins in man.</strong> Nature 302: 540-543, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6339950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6339950</a>] [<a href="https://doi.org/10.1038/302540a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6339950">Shoelson et al. (1983)</a> and <a href="#6" class="mim-tip-reference" title="Gruppuso, P. A., Gorden, P., Kahn, C. R., Cornblath, M., Zeller, W. P., Schwartz, R. <strong>Familial hyperproinsulinemia due to a proposed defect in conversion of proinsulin to insulin.</strong> New Eng. J. Med. 311: 629-634, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6382002/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6382002</a>] [<a href="https://doi.org/10.1056/NEJM198409063111003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6382002">Gruppuso et al. (1984)</a> was consistent with autosomal dominant inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6339950+6382002" 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="#14" class="mim-tip-reference" title="Tager, H., Given, B., Baldwin, D., Mako, M., Markese, J., Rubenstein, A., Olefsky, J., Kobayashi, M., Kolterman, O., Poucher, R. <strong>A structurally abnormal insulin causing human diabetes.</strong> Nature 281: 122-125, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/381941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">381941</a>] [<a href="https://doi.org/10.1038/281122a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="381941">Tager et al. (1979)</a> studied insulin isolated from the pancreas of a diabetic patient and concluded that one of the allelic genes had undergone a mutation resulting in substitution of leucine for phenylalanine at position 23 or 24 in the insulin B chain. Occurring in the invariant portion of the molecule, the mutation resulted in reduced biologic activity (<a href="#5" class="mim-tip-reference" title="Given, B. D., Mako, M. E., Tager, H. S., Baldwin, D., Markese, J., Rubenstein, A. H., Olefsky, J., Kobayashi, M., Kolterman, O., Poucher, R. <strong>Diabetes due to secretion of an abnormal insulin.</strong> New Eng. J. Med. 302: 129-135, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7350438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7350438</a>] [<a href="https://doi.org/10.1056/NEJM198001173020301" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7350438">Given et al., 1980</a>). <a href="#11" class="mim-tip-reference" title="Kwok, S. C. M., Chan, S. J., Rubenstein, A. H., Poucher, R., Steiner, D. F. <strong>Loss of a restriction endonuclease cleavage site in the gene of a structurally abnormal human insulin.</strong> Biochem. Biophys. Res. Commun. 98: 844-849, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6261753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6261753</a>] [<a href="https://doi.org/10.1016/0006-291x(81)91188-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6261753">Kwok et al. (1981)</a> isolated genomic DNA from the leukocytes of a diabetic patient with the mutant insulin identified by <a href="#5" class="mim-tip-reference" title="Given, B. D., Mako, M. E., Tager, H. S., Baldwin, D., Markese, J., Rubenstein, A. H., Olefsky, J., Kobayashi, M., Kolterman, O., Poucher, R. <strong>Diabetes due to secretion of an abnormal insulin.</strong> New Eng. J. Med. 302: 129-135, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7350438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7350438</a>] [<a href="https://doi.org/10.1056/NEJM198001173020301" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7350438">Given et al. (1980)</a>. After digestion with restriction endonuclease MboII, electrophoresis, and hybridization with cloned human cDNA probes, one MboII cleavage site had been lost, which is consistent with the postulated replacement of phenylalanine by leucine at position 24 of the insulin gene. <a href="#13" class="mim-tip-reference" title="Shoelson, S., Haneda, M., Blix, P., Nanjo, A., Sanke, T., Inouye, K., Steiner, D., Rubenstein, A., Tager, H. <strong>Three mutant insulins in man.</strong> Nature 302: 540-543, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6339950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6339950</a>] [<a href="https://doi.org/10.1038/302540a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6339950">Shoelson et al. (1983)</a> demonstrated that the substitution in the mutant insulin identified by <a href="#14" class="mim-tip-reference" title="Tager, H., Given, B., Baldwin, D., Mako, M., Markese, J., Rubenstein, A., Olefsky, J., Kobayashi, M., Kolterman, O., Poucher, R. <strong>A structurally abnormal insulin causing human diabetes.</strong> Nature 281: 122-125, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/381941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">381941</a>] [<a href="https://doi.org/10.1038/281122a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="381941">Tager et al. (1979)</a> and <a href="#5" class="mim-tip-reference" title="Given, B. D., Mako, M. E., Tager, H. S., Baldwin, D., Markese, J., Rubenstein, A. H., Olefsky, J., Kobayashi, M., Kolterman, O., Poucher, R. <strong>Diabetes due to secretion of an abnormal insulin.</strong> New Eng. J. Med. 302: 129-135, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7350438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7350438</a>] [<a href="https://doi.org/10.1056/NEJM198001173020301" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7350438">Given et al. (1980)</a> is leucine for phenylalanine at B25 (<a href="/entry/176730#0001">176730.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=381941+6261753+6339950+7350438" 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 patient with hyperproinsulinemia, <a href="#13" class="mim-tip-reference" title="Shoelson, S., Haneda, M., Blix, P., Nanjo, A., Sanke, T., Inouye, K., Steiner, D., Rubenstein, A., Tager, H. <strong>Three mutant insulins in man.</strong> Nature 302: 540-543, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6339950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6339950</a>] [<a href="https://doi.org/10.1038/302540a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6339950">Shoelson et al. (1983)</a> identified a substitution of serine for phenylalanine at position 24 of the insulin B chain (<a href="/entry/176730#0002">176730.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6339950" 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 patient with mild diabetes, marked fasting hyperinsulinemia, and a reduced fasting C-peptide:insulin molar ratio, Haneda et al. (<a href="#7" class="mim-tip-reference" title="Haneda, M., Chan, S. J., Kwok, S. C. M., Rubenstein, A. H., Steiner, D. F. <strong>Studies on mutant human insulin genes: identification and sequence analysis of a gene encoding (ser-B24) insulin.</strong> Proc. Nat. Acad. Sci. 80: 6366-6370, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6312455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6312455</a>] [<a href="https://doi.org/10.1073/pnas.80.20.6366" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6312455">1983</a>, <a href="#8" class="mim-tip-reference" title="Haneda, M., Polonsky, K. S., Bergenstal, R. M., Jaspan, J. B., Shoelson, S. E., Blix, P. M., Chan, S. J., Kwok, S. C. M., Wishner, W. B., Zeidler, A., Olefsky, J. M., Freidenberg, G., Tager, H. S., Steiner, D. F., Rubenstein, A. H. <strong>Familial hyperinsulinemia due to a structurally abnormal insulin: definition of an emerging new clinical syndrome.</strong> New Eng. J. Med. 310: 1288-1294, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6371526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6371526</a>] [<a href="https://doi.org/10.1056/NEJM198405173102004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6371526">1984</a>) found heterozygosity for the ser24-to-phe mutation in the insulin B chain. The patient, who was found to have abnormal circulating insulin molecules that could be distinguished from each other and from normal insulin, responded normally to exogenous insulin. Five additional family members of both sexes in 3 generations were affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6371526+6312455" 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 affected members of the family with hyperproinsulinemia reported by <a href="#6" class="mim-tip-reference" title="Gruppuso, P. A., Gorden, P., Kahn, C. R., Cornblath, M., Zeller, W. P., Schwartz, R. <strong>Familial hyperproinsulinemia due to a proposed defect in conversion of proinsulin to insulin.</strong> New Eng. J. Med. 311: 629-634, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6382002/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6382002</a>] [<a href="https://doi.org/10.1056/NEJM198409063111003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6382002">Gruppuso et al. (1984)</a>, <a href="#1" class="mim-tip-reference" title="Chan, S. J., Seino, S., Gruppuso, P. A., Schwartz, R., Steiner, D. F. <strong>A mutation in the B chain coding region is associated with impaired proinsulin conversion in a family with hyperproinsulinemia.</strong> Proc. Nat. Acad. Sci. 84: 2194-2197, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3470784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3470784</a>] [<a href="https://doi.org/10.1073/pnas.84.8.2194" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3470784">Chan et al. (1987)</a> identified a heterozygous missense mutation in the B chain of the INS gene (H10D; <a href="/entry/176730#0003">176730.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6382002+3470784" 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 href="#Gabbay1980" class="mim-tip-reference" title="Gabbay, K. H. <strong>The insulinopathies. (Editorial)</strong> New Eng. J. Med. 302: 165-167, 1980.">Gabbay (1980)</a>; <a href="#Kanazawa1979" class="mim-tip-reference" title="Kanazawa, Y., Hayashi, M., Ikeuchi, M., Kasuga, M., Oka, Y., Sato, H., Hiramatsu, K., Kosaka, K. <strong>Familial proinsulinemia: a rare disorder of insulin biosynthesis.In: Baba, S.; Kaneko, T.; Yanaihara, N. : Proc. Symp. on proinsulin, insulin, and C-peptide. Tokushima, Japan, 1978.</strong> Amsterdam: Excerpta Medica (pub.) 1979. Pp. 262-269.">Kanazawa et al. (1979)</a>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3470784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3470784</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3470784" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7350441/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7350441</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7350441" 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/10.1056/NEJM198001173020308" target="_blank">Full Text</a>]
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<a id="3" class="mim-anchor"></a>
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<a id="Gabbay1979" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Gabbay, K. H., Bergenstal, R. M., Wolff, J., Mako, M. E., Rubenstein, A. H.
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<strong>Familial hyperproinsulinemia: partial characterization of circulating proinsulin-like material.</strong>
|
|
Proc. Nat. Acad. Sci. 76: 2881-2885, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/288074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">288074</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=288074" 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/10.1073/pnas.76.6.2881" target="_blank">Full Text</a>]
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<a id="4" class="mim-anchor"></a>
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<a id="Gabbay1976" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Gabbay, K. H., DeLuca, K., Fisher, J. N., Jr., Mako, M. E., Rubenstein, A. H.
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<strong>Familial hyperproinsulinemia: an autosomal dominant defect.</strong>
|
|
New Eng. J. Med. 294: 911-915, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/815812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">815812</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=815812" 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/10.1056/NEJM197604222941701" target="_blank">Full Text</a>]
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<a id="5" class="mim-anchor"></a>
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<a id="Given1980" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Given, B. D., Mako, M. E., Tager, H. S., Baldwin, D., Markese, J., Rubenstein, A. H., Olefsky, J., Kobayashi, M., Kolterman, O., Poucher, R.
|
|
<strong>Diabetes due to secretion of an abnormal insulin.</strong>
|
|
New Eng. J. Med. 302: 129-135, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7350438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7350438</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7350438" 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/10.1056/NEJM198001173020301" target="_blank">Full Text</a>]
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<a id="6" class="mim-anchor"></a>
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<a id="Gruppuso1984" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Gruppuso, P. A., Gorden, P., Kahn, C. R., Cornblath, M., Zeller, W. P., Schwartz, R.
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<strong>Familial hyperproinsulinemia due to a proposed defect in conversion of proinsulin to insulin.</strong>
|
|
New Eng. J. Med. 311: 629-634, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6382002/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6382002</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6382002" 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/10.1056/NEJM198409063111003" target="_blank">Full Text</a>]
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<a id="7" class="mim-anchor"></a>
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<a id="Haneda1983" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Haneda, M., Chan, S. J., Kwok, S. C. M., Rubenstein, A. H., Steiner, D. F.
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<strong>Studies on mutant human insulin genes: identification and sequence analysis of a gene encoding (ser-B24) insulin.</strong>
|
|
Proc. Nat. Acad. Sci. 80: 6366-6370, 1983.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6312455/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6312455</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6312455" 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/10.1073/pnas.80.20.6366" target="_blank">Full Text</a>]
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<a id="8" class="mim-anchor"></a>
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<a id="Haneda1984" class="mim-anchor"></a>
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<div class="">
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Haneda, M., Polonsky, K. S., Bergenstal, R. M., Jaspan, J. B., Shoelson, S. E., Blix, P. M., Chan, S. J., Kwok, S. C. M., Wishner, W. B., Zeidler, A., Olefsky, J. M., Freidenberg, G., Tager, H. S., Steiner, D. F., Rubenstein, A. H.
|
|
<strong>Familial hyperinsulinemia due to a structurally abnormal insulin: definition of an emerging new clinical syndrome.</strong>
|
|
New Eng. J. Med. 310: 1288-1294, 1984.
|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6371526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6371526</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6371526" 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/10.1056/NEJM198405173102004" target="_blank">Full Text</a>]
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<a id="9" class="mim-anchor"></a>
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<a id="Kanazawa1978" class="mim-anchor"></a>
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<div class="">
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Kanazawa, Y., Hayashi, M., Ikeuchi, M., Hiramatsu, K., Kosaka, K.
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<strong>Familial proinsulinemia: a possible cause of abnormal glucose tolerance. (Abstract)</strong>
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|
Europ. J. Clin. Invest. 8: 327, 1978.
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<a id="10" class="mim-anchor"></a>
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<a id="Kanazawa1979" class="mim-anchor"></a>
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Kanazawa, Y., Hayashi, M., Ikeuchi, M., Kasuga, M., Oka, Y., Sato, H., Hiramatsu, K., Kosaka, K.
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<strong>Familial proinsulinemia: a rare disorder of insulin biosynthesis.In: Baba, S.; Kaneko, T.; Yanaihara, N. : Proc. Symp. on proinsulin, insulin, and C-peptide. Tokushima, Japan, 1978.</strong>
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Amsterdam: Excerpta Medica (pub.) 1979. Pp. 262-269.
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<a id="11" class="mim-anchor"></a>
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<a id="Kwok1981" class="mim-anchor"></a>
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<div class="">
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Kwok, S. C. M., Chan, S. J., Rubenstein, A. H., Poucher, R., Steiner, D. F.
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<strong>Loss of a restriction endonuclease cleavage site in the gene of a structurally abnormal human insulin.</strong>
|
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Biochem. Biophys. Res. Commun. 98: 844-849, 1981.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6261753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6261753</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6261753" 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/10.1016/0006-291x(81)91188-8" target="_blank">Full Text</a>]
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<a id="12" class="mim-anchor"></a>
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<a id="Shoelson1983" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Shoelson, S., Fickova, M., Haneda, M., Nahum, A., Musso, G., Kaiser, E. T., Rubenstein, A. H., Tager, H.
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<strong>Identification of a mutant human insulin predicted to contain a serine-for-phenylalanine substitution.</strong>
|
|
Proc. Nat. Acad. Sci. 80: 7390-7394, 1983.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6424111/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6424111</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6424111" 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/10.1073/pnas.80.24.7390" target="_blank">Full Text</a>]
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<a id="Shoelson1983" class="mim-anchor"></a>
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<div class="">
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Shoelson, S., Haneda, M., Blix, P., Nanjo, A., Sanke, T., Inouye, K., Steiner, D., Rubenstein, A., Tager, H.
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<strong>Three mutant insulins in man.</strong>
|
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Nature 302: 540-543, 1983.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6339950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6339950</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6339950" 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/10.1038/302540a0" target="_blank">Full Text</a>]
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<a id="14" class="mim-anchor"></a>
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<a id="Tager1979" class="mim-anchor"></a>
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<div class="">
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Tager, H., Given, B., Baldwin, D., Mako, M., Markese, J., Rubenstein, A., Olefsky, J., Kobayashi, M., Kolterman, O., Poucher, R.
|
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<strong>A structurally abnormal insulin causing human diabetes.</strong>
|
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Nature 281: 122-125, 1979.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/381941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">381941</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=381941" 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/10.1038/281122a0" target="_blank">Full Text</a>]
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<a id="15" class="mim-anchor"></a>
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<a id="Vinik1986" class="mim-anchor"></a>
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<div class="">
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Vinik, A. I., Seino, S., Funakoshi, A., Schwartz, J., Matsumoto, M., Schteingart, D. E., Fu, Z.-Z., Tsai, S.-T.
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<strong>Familial hyperinsulinemia associated with secretion of an abnormal insulin, and coexistence of insulin resistance in the propositus.</strong>
|
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J. Clin. Endocr. Metab. 62: 645-652, 1986.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3512591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3512591</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3512591" 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/10.1210/jcem-62-4-645" target="_blank">Full Text</a>]
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<a id="16" class="mim-anchor"></a>
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<a id="Warren-Perry1997" class="mim-anchor"></a>
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<div class="">
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Warren-Perry, M. G., Manley, S. E., Ostrega, D., Polonsky, K., Mussett, S., Brown, P., Turner, R. C.
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<strong>A novel point mutation in the insulin gene giving rise to hyperproinsulinemia.</strong>
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J. Clin. Endocr. Metab. 82: 1629-1631, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9141561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9141561</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9141561" 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/10.1210/jcem.82.5.3914" target="_blank">Full Text</a>]
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Carol A. Bocchini : 2/4/2015
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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carol : 02/06/2015
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carol : 2/5/2015<br>carol : 2/5/2015
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<strong>#</strong> 616214
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HYPERPROINSULINEMIA
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<strong>SNOMEDCT:</strong> 237613005;
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<strong>Phenotype-Gene Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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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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</th>
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<th>
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|
Gene/Locus <br /> MIM number
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
|
|
11p15.5
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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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Hyperproinsulinemia
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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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616214
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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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|
Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
3
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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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|
INS
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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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176730
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<span class="mim-text-font">
|
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<p>A number sign (#) is used with this entry because hyperproinsulinemia is caused by heterozygous mutation in the INS gene (176730) on chromosome 11p15.</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Insulin (INS; 176730) is produced posttranslationally from its precursor molecule, proinsulin, by site-directed proteolysis in beta-cell granules. Conversion involves cleavage at pairs of basic residues that link both the insulin A and B chains to C-peptide. Human proinsulin conversion has a preferred sequential route, such that cleavage at the B-chain/C-peptide junction occurs first, producing des-31,32 split proinsulin as the major conversion intermediate. Under normal circumstances, proinsulin conversion is largely completed before secretion, and low plasma levels of intact proinsulin and conversion intermediates are found. Structural abnormalities in the proinsulin molecule can impair conversion, leading to the accumulation of proinsulin-like material in the circulation. Such defects show an autosomal dominant mode of inheritance and are the main cause of familial hyperproinsulinemia (summary by Warren-Perry et al., 1997). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>Clinical Features</strong>
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</span>
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>Gabbay et al. (1976) described a family in which many persons in an autosomal dominant pattern had proinsulin or a proinsulin-like material as the major fraction of circulating insulin immunoreactivity in both the fasting and the stimulated state. The hyperproinsulinemia was asymptomatic, with no evident relation to hypoglycemia or development of diabetes mellitus. In light of the dominant inheritance, the authors thought a structural abnormality of proinsulin to be more likely than deficiency of the proinsulin cleaving enzyme (or enzymes). </p><p>Gabbay et al. (1979) presented data indicating that proinsulin in familial hyperproinsulinemia indeed has a structural abnormality such that cleavage at the B chain/C peptide site is impaired. Kanazawa et al. (1978) described the counterpart of the defect reported by Gabbay et al. (1976, 1979): hyperproinsulinemia due to mutation at the cleavage site connecting the A chain to the C peptide. Inheritance was again autosomal dominant. </p><p>Shoelson et al. (1983) studied 3 unrelated patients, 1 of whom was previously reported by Tager et al. (1979) and 1 of whom was previously reported by Shoelson et al. (1983), with diabetes-type hyperglycemia and marked hyperinsulinemia suggestive of insulin resistance but with normal response to exogenously administered insulin. Because the opportunity to study pancreatic tissue was rare, the authors developed a method combining high pressure liquid chromatography and radioimmunoassay. By this method, each of the 3 patients was found to secrete a structurally variant and chemically distinct insulin. All 3 patients were heterozygous. Two patients came from families in which many members of several generations had the variant insulin in an autosomal dominant pedigree pattern and had either normal or very mildly impaired glucose tolerance. </p><p>Gruppuso et al. (1984) identified a hyperproinsulinemia kindred in which the proband, a 14-year-old girl with a history of transient hyperglycemia at age 2 years, was studied for symptoms of hypoglycemia. Elevated levels of proinsulin were found in her and 2 sibs, her father, and her paternal grandfather, whereas 4 other close relatives were normal. Gruppuso et al. (1984) suggested that hyperproinsulinemia present in 5 persons in 3 consecutive generations with male-to-male transmission was due not to a structural defect of the proinsulin molecule but to a defect in the conversion mechanism in the pancreas. </p><p>In 4 persons in 2 generations, Vinik et al. (1986) described a structural defect of insulin associated with hyperinsulinemia. The insulin was found to elute later than normal human insulin on reverse phase high performance liquid chromatography. It was more hydrophobic than normal human insulin and had only 10% of the activity of normal insulin in terms of ability to bind to isolated rat adipocytes and stimulate glucose metabolism in them. The proband, aged 45 years, had a 9-year history of syncopal attacks. He showed resistance to exogenous insulin. Plasma counterregulatory hormones (glucagon, growth hormone, cortisol, epinephrine, norepinephrine) showed normal concentrations. Binding of exogenous insulin by the patient's cells was normal. The abnormal insulin was demonstrated in 2 of 3 sons and in a sister but not in the mother, brother, or niece. Sensitivity to insulin was normal in the 2 sons who had abnormal insulin. The explanation for the insulin resistance in the proband was unclear. The authors thought that the change in the insulin molecule in this family was different from either the B24 phe-to-ser (176730.0002) or the B25 phe-to-leu (176730.0001) mutations previously described. </p>
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</span>
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<div>
|
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<br />
|
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</div>
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The transmission pattern of hyperproinsulinemia in the families reported by Shoelson et al. (1983) and Gruppuso et al. (1984) was consistent with autosomal dominant inheritance. </p>
|
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</span>
|
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<div>
|
|
<br />
|
|
</div>
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|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
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</h4>
|
|
</div>
|
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|
|
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|
|
<span class="mim-text-font">
|
|
<p>Tager et al. (1979) studied insulin isolated from the pancreas of a diabetic patient and concluded that one of the allelic genes had undergone a mutation resulting in substitution of leucine for phenylalanine at position 23 or 24 in the insulin B chain. Occurring in the invariant portion of the molecule, the mutation resulted in reduced biologic activity (Given et al., 1980). Kwok et al. (1981) isolated genomic DNA from the leukocytes of a diabetic patient with the mutant insulin identified by Given et al. (1980). After digestion with restriction endonuclease MboII, electrophoresis, and hybridization with cloned human cDNA probes, one MboII cleavage site had been lost, which is consistent with the postulated replacement of phenylalanine by leucine at position 24 of the insulin gene. Shoelson et al. (1983) demonstrated that the substitution in the mutant insulin identified by Tager et al. (1979) and Given et al. (1980) is leucine for phenylalanine at B25 (176730.0001). </p><p>In a patient with hyperproinsulinemia, Shoelson et al. (1983) identified a substitution of serine for phenylalanine at position 24 of the insulin B chain (176730.0002). </p><p>In a patient with mild diabetes, marked fasting hyperinsulinemia, and a reduced fasting C-peptide:insulin molar ratio, Haneda et al. (1983, 1984) found heterozygosity for the ser24-to-phe mutation in the insulin B chain. The patient, who was found to have abnormal circulating insulin molecules that could be distinguished from each other and from normal insulin, responded normally to exogenous insulin. Five additional family members of both sexes in 3 generations were affected. </p><p>In affected members of the family with hyperproinsulinemia reported by Gruppuso et al. (1984), Chan et al. (1987) identified a heterozygous missense mutation in the B chain of the INS gene (H10D; 176730.0003). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Gabbay (1980); Kanazawa et al. (1979)
|
|
</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">
|
|
Chan, S. J., Seino, S., Gruppuso, P. A., Schwartz, R., Steiner, D. F.
|
|
<strong>A mutation in the B chain coding region is associated with impaired proinsulin conversion in a family with hyperproinsulinemia.</strong>
|
|
Proc. Nat. Acad. Sci. 84: 2194-2197, 1987.
|
|
|
|
|
|
[PubMed: 3470784]
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|
|
[Full Text: https://doi.org/10.1073/pnas.84.8.2194]
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gabbay, K. H.
|
|
<strong>The insulinopathies. (Editorial)</strong>
|
|
New Eng. J. Med. 302: 165-167, 1980.
|
|
|
|
|
|
[PubMed: 7350441]
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|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198001173020308]
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gabbay, K. H., Bergenstal, R. M., Wolff, J., Mako, M. E., Rubenstein, A. H.
|
|
<strong>Familial hyperproinsulinemia: partial characterization of circulating proinsulin-like material.</strong>
|
|
Proc. Nat. Acad. Sci. 76: 2881-2885, 1979.
|
|
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|
|
[PubMed: 288074]
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|
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[Full Text: https://doi.org/10.1073/pnas.76.6.2881]
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gabbay, K. H., DeLuca, K., Fisher, J. N., Jr., Mako, M. E., Rubenstein, A. H.
|
|
<strong>Familial hyperproinsulinemia: an autosomal dominant defect.</strong>
|
|
New Eng. J. Med. 294: 911-915, 1976.
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|
|
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|
|
[PubMed: 815812]
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|
|
[Full Text: https://doi.org/10.1056/NEJM197604222941701]
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Given, B. D., Mako, M. E., Tager, H. S., Baldwin, D., Markese, J., Rubenstein, A. H., Olefsky, J., Kobayashi, M., Kolterman, O., Poucher, R.
|
|
<strong>Diabetes due to secretion of an abnormal insulin.</strong>
|
|
New Eng. J. Med. 302: 129-135, 1980.
|
|
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|
|
|
[PubMed: 7350438]
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|
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|
|
[Full Text: https://doi.org/10.1056/NEJM198001173020301]
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|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gruppuso, P. A., Gorden, P., Kahn, C. R., Cornblath, M., Zeller, W. P., Schwartz, R.
|
|
<strong>Familial hyperproinsulinemia due to a proposed defect in conversion of proinsulin to insulin.</strong>
|
|
New Eng. J. Med. 311: 629-634, 1984.
|
|
|
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|
|
[PubMed: 6382002]
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|
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|
|
[Full Text: https://doi.org/10.1056/NEJM198409063111003]
|
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Haneda, M., Chan, S. J., Kwok, S. C. M., Rubenstein, A. H., Steiner, D. F.
|
|
<strong>Studies on mutant human insulin genes: identification and sequence analysis of a gene encoding (ser-B24) insulin.</strong>
|
|
Proc. Nat. Acad. Sci. 80: 6366-6370, 1983.
|
|
|
|
|
|
[PubMed: 6312455]
|
|
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|
|
[Full Text: https://doi.org/10.1073/pnas.80.20.6366]
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Haneda, M., Polonsky, K. S., Bergenstal, R. M., Jaspan, J. B., Shoelson, S. E., Blix, P. M., Chan, S. J., Kwok, S. C. M., Wishner, W. B., Zeidler, A., Olefsky, J. M., Freidenberg, G., Tager, H. S., Steiner, D. F., Rubenstein, A. H.
|
|
<strong>Familial hyperinsulinemia due to a structurally abnormal insulin: definition of an emerging new clinical syndrome.</strong>
|
|
New Eng. J. Med. 310: 1288-1294, 1984.
|
|
|
|
|
|
[PubMed: 6371526]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198405173102004]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kanazawa, Y., Hayashi, M., Ikeuchi, M., Hiramatsu, K., Kosaka, K.
|
|
<strong>Familial proinsulinemia: a possible cause of abnormal glucose tolerance. (Abstract)</strong>
|
|
Europ. J. Clin. Invest. 8: 327, 1978.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kanazawa, Y., Hayashi, M., Ikeuchi, M., Kasuga, M., Oka, Y., Sato, H., Hiramatsu, K., Kosaka, K.
|
|
<strong>Familial proinsulinemia: a rare disorder of insulin biosynthesis.In: Baba, S.; Kaneko, T.; Yanaihara, N. : Proc. Symp. on proinsulin, insulin, and C-peptide. Tokushima, Japan, 1978.</strong>
|
|
Amsterdam: Excerpta Medica (pub.) 1979. Pp. 262-269.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kwok, S. C. M., Chan, S. J., Rubenstein, A. H., Poucher, R., Steiner, D. F.
|
|
<strong>Loss of a restriction endonuclease cleavage site in the gene of a structurally abnormal human insulin.</strong>
|
|
Biochem. Biophys. Res. Commun. 98: 844-849, 1981.
|
|
|
|
|
|
[PubMed: 6261753]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0006-291x(81)91188-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shoelson, S., Fickova, M., Haneda, M., Nahum, A., Musso, G., Kaiser, E. T., Rubenstein, A. H., Tager, H.
|
|
<strong>Identification of a mutant human insulin predicted to contain a serine-for-phenylalanine substitution.</strong>
|
|
Proc. Nat. Acad. Sci. 80: 7390-7394, 1983.
|
|
|
|
|
|
[PubMed: 6424111]
|
|
|
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|
|
[Full Text: https://doi.org/10.1073/pnas.80.24.7390]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shoelson, S., Haneda, M., Blix, P., Nanjo, A., Sanke, T., Inouye, K., Steiner, D., Rubenstein, A., Tager, H.
|
|
<strong>Three mutant insulins in man.</strong>
|
|
Nature 302: 540-543, 1983.
|
|
|
|
|
|
[PubMed: 6339950]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/302540a0]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tager, H., Given, B., Baldwin, D., Mako, M., Markese, J., Rubenstein, A., Olefsky, J., Kobayashi, M., Kolterman, O., Poucher, R.
|
|
<strong>A structurally abnormal insulin causing human diabetes.</strong>
|
|
Nature 281: 122-125, 1979.
|
|
|
|
|
|
[PubMed: 381941]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/281122a0]
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|
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</p>
|
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</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vinik, A. I., Seino, S., Funakoshi, A., Schwartz, J., Matsumoto, M., Schteingart, D. E., Fu, Z.-Z., Tsai, S.-T.
|
|
<strong>Familial hyperinsulinemia associated with secretion of an abnormal insulin, and coexistence of insulin resistance in the propositus.</strong>
|
|
J. Clin. Endocr. Metab. 62: 645-652, 1986.
|
|
|
|
|
|
[PubMed: 3512591]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem-62-4-645]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Warren-Perry, M. G., Manley, S. E., Ostrega, D., Polonsky, K., Mussett, S., Brown, P., Turner, R. C.
|
|
<strong>A novel point mutation in the insulin gene giving rise to hyperproinsulinemia.</strong>
|
|
J. Clin. Endocr. Metab. 82: 1629-1631, 1997.
|
|
|
|
|
|
[PubMed: 9141561]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.82.5.3914]
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</p>
|
|
</li>
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</ol>
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<div>
|
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<br />
|
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</div>
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</div>
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</div>
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<div>
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<div class="row">
|
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
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<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
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Carol A. Bocchini : 2/4/2015
|
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</span>
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</div>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div class="row">
|
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
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<span class="text-nowrap mim-text-font">
|
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Edit History:
|
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</span>
|
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
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carol : 02/06/2015<br>carol : 2/5/2015<br>carol : 2/5/2015
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</span>
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</div>
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</div>
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