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Entry
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- #204100 - LEBER CONGENITAL AMAUROSIS 2; LCA2
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- OMIM
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<p>
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<span class="h4">#204100</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<li role="presentation">
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<a href="/clinicalSynopsis/204100"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS204000"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#clinicalManagement">Clinical Management</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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</nav>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=LEBER CONGENITAL AMAUROSIS" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=3243&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="#mimGeneReviewsFold" id="mimGeneReviewsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling."><span id="mimGeneReviewsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Gene Reviews</div>
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<div id="mimGeneReviewsFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.ncbi.nlm.nih.gov/books/NBK531510/" title="Leber Congenital Amaurosis / Early-Onset Severe Retinal Dystrophy Overview" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Leber Congenital Amaurosis…</a></div><div style="margin-left: 0.5em;"><a href="https://www.ncbi.nlm.nih.gov/books/NBK549574/" title="RPE65-Related Leber Congenital Amaurosis / Early-Onset Severe Retinal Dystrophy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">RPE65-Related Leber Congen…</a></div>
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</div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=204100[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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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=65" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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</div>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0110016" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="http://www.informatics.jax.org/disease/204100" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://omia.org/OMIA001222/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0110016" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</a>
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</span>
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</span>
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<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:204100" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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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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</span>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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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>ORPHA:</strong> 65<br />
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<strong>DO:</strong> 0110016<br />
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">ICD+</a>
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</div>
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<div>
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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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204100
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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LEBER CONGENITAL AMAUROSIS 2; LCA2
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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AMAUROSIS CONGENITA OF LEBER II
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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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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Location
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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
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/1/706?start=-3&limit=10&highlight=706">
|
|
1p31.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Leber congenital amaurosis 2
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/204100"> 204100 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
RPE65
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/180069"> 180069 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/204100" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
|
|
<a href="/phenotypicSeries/PS204000" class="btn btn-info" role="button"> Phenotypic Series </a>
|
|
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/204100" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/204100" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Nystagmus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/563001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">563001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/379.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">379.50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0028738&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028738</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span><br /> -
|
|
Hypermetropia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/38101003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">38101003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H52.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H52.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/367.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">367.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020490&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020490</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000540" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000540</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000540" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000540</a>]</span><br /> -
|
|
Myopia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/57190000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">57190000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H52.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H52.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/367.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">367.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0027092&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027092</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000545" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000545</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000545" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000545</a>]</span><br /> -
|
|
Strabismus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22066006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22066006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H50.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H50.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H50.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H50.40</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038379&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038379</a>, <a href="https://bioportal.bioontology.org/search?q=C2020541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2020541</a>, <a href="https://bioportal.bioontology.org/search?q=C1423541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1423541</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000486</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000486" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000486</a>]</span><br /> -
|
|
Hypopigmented fundus <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856885&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856885</a>]</span><br /> -
|
|
Mottled pigmentation in periphery <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5232320&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5232320</a>]</span><br /> -
|
|
Attenuated retinal vessels <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3151109&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3151109</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007843" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007843</a>]</span><br /> -
|
|
Pale optic disc <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302200001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302200001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0554970&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0554970</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000543" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000543</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000543" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000543</a>]</span><br /> -
|
|
Blindness <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0456909&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0456909</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000618" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000618</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000618" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000618</a>]</span><br /> -
|
|
Reduced or nondetectable electroretinogram (ERG) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5232321&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5232321</a>]</span><br /> -
|
|
Significantly reduced or absent scotopic and photopic responses seen on ERG <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5232322&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5232322</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Neck </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Torticollis (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/70070008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">70070008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M43.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M43.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/723.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">723.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0040485&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040485</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000473" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000473</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000473" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000473</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
|
|
|
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|
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|
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|
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|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Psychomotor retardation (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398991009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398991009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1144814003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1144814003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0424230&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424230</a>, <a href="https://bioportal.bioontology.org/search?q=C5441816&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5441816</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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<div>
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<span class="h5 mim-font">
|
|
<em> Behavioral Psychiatric Manifestations </em>
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</span>
|
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</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
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|
|
- Autistic-like contact disorder (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5232319&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5232319</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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</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> MISCELLANEOUS </strong>
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</span>
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</div>
|
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<div style="margin-left: 2em;">
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<div>
|
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<span class="mim-font">
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|
|
- Onset in infancy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848924&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848924</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span><br /> -
|
|
Progressive disorder <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864985&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864985</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003676" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003676</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003676" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003676</a>]</span><br /> -
|
|
Founder mutation (<a href="/entry/180069#0009">180069.0009</a>) discovered in an isolated Dutch population<br />
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|
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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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<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
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</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
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|
|
- Caused by mutation in the RPE65 retinoid isomerohydrolase gene (RPE65, <a href="/entry/180069#0001">180069.0001</a>)<br />
|
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|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
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</div>
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|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
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|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
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|
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<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Leber congenital amaurosis
|
|
- <a href="/phenotypicSeries/PS204000">PS204000</a>
|
|
- 26 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
|
|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/132?start=-3&limit=10&highlight=132"> 1p36.22 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608553"> Leber congenital amaurosis 9 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608553"> 608553 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608700"> NMNAT1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608700"> 608700 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/706?start=-3&limit=10&highlight=706"> 1p31.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/204100"> Leber congenital amaurosis 2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/204100"> 204100 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/180069"> RPE65 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/180069"> 180069 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/1536?start=-3&limit=10&highlight=1536"> 1q31.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613835"> Leber congenital amaurosis 8 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613835"> 613835 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604210"> CRB1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604210"> 604210 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/1678?start=-3&limit=10&highlight=1678"> 1q32.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610612"> Leber congenital amaurosis 12 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610612"> 610612 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/180040"> RD3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/180040"> 180040 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/2/1119?start=-3&limit=10&highlight=1119"> 2q37.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614186"> Leber congenital amaurosis 16 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614186"> 614186 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603208"> KCNJ13 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603208"> 603208 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/4/623?start=-3&limit=10&highlight=623"> 4q32.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613341"> Retinitis pigmentosa, juvenile </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613341"> 613341 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604863"> LRAT </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604863"> 604863 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/4/623?start=-3&limit=10&highlight=623"> 4q32.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613341"> Retinal dystrophy, early-onset severe </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613341"> 613341 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604863"> LRAT </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604863"> 604863 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/4/623?start=-3&limit=10&highlight=623"> 4q32.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613341"> Leber congenital amaurosis 14 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613341"> 613341 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604863"> LRAT </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604863"> 604863 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/6/430?start=-3&limit=10&highlight=430"> 6p21.31 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613843"> Leber congenital amaurosis 15 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613843"> 613843 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602280"> TULP1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602280"> 602280 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/6/502?start=-3&limit=10&highlight=502"> 6p21.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608133"> Retinitis pigmentosa 7 and digenic form </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>, <abbr class="mim-tip-hint" title="Digenic dominant">DD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608133"> 608133 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/179605"> PRPH2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/179605"> 179605 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/6/502?start=-3&limit=10&highlight=502"> 6p21.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608133"> Leber congenital amaurosis 18 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>, <abbr class="mim-tip-hint" title="Digenic dominant">DD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608133"> 608133 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/179605"> PRPH2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/179605"> 179605 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/6/665?start=-3&limit=10&highlight=665"> 6q14.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604537"> Leber congenital amaurosis 5 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604537"> 604537 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611408"> LCA5 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611408"> 611408 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/6/726?start=-3&limit=10&highlight=726"> 6q16.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618513"> ?Leber congenital amaurosis 19 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618513"> 618513 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618439"> USP45 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618439"> 618439 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/7/651?start=-3&limit=10&highlight=651"> 7q32.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613837"> Leber congenital amaurosis 11 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613837"> 613837 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/146690"> IMPDH1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/146690"> 146690 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/8/420?start=-3&limit=10&highlight=420"> 8q22.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615360"> Leber congenital amaurosis 17 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615360"> 615360 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601147"> GDF6 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601147"> 601147 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/11/482?start=-3&limit=10&highlight=482"> 11q12.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608133"> Retinitis pigmentosa 7, digenic form </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>, <abbr class="mim-tip-hint" title="Digenic dominant">DD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608133"> 608133 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/180721"> ROM1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/180721"> 180721 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/12/664?start=-3&limit=10&highlight=664"> 12q21.32 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611755"> Leber congenital amaurosis 10 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611755"> 611755 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610142"> CEP290 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610142"> 610142 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/14/52?start=-3&limit=10&highlight=52"> 14q11.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613826"> Leber congenital amaurosis 6 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613826"> 613826 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605446"> RPGRIP1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605446"> 605446 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/14/332?start=-3&limit=10&highlight=332"> 14q24.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612712"> Leber congenital amaurosis 13 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612712"> 612712 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608830"> RDH12 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/608830"> 608830 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/14/437?start=-3&limit=10&highlight=437"> 14q31.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604232"> Retinitis pigmentosa 94, variable age at onset, autosomal recessive </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604232"> 604232 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609868"> SPATA7 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609868"> 609868 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/14/437?start=-3&limit=10&highlight=437"> 14q31.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604232"> Leber congenital amaurosis 3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604232"> 604232 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609868"> SPATA7 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609868"> 609868 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/17/115?start=-3&limit=10&highlight=115"> 17p13.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
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<a href="/entry/604393"> Leber congenital amaurosis 4 </a>
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<a href="/entry/613829"> Leber congenital amaurosis 7 </a>
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<p>A number sign (#) is used with this entry because of evidence that Leber congenital amaurosis-2 (LCA2) is caused by homozygous or compound heterozygous mutation in the RPE65 gene (<a href="/entry/180069">180069</a>) on chromosome 1p31.</p><p>Mutations in this gene also cause retinitis pigmentosa (RP20; <a href="/entry/613794">613794</a>).</p>
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<p>Leber congenital amaurosis comprises a group of early-onset childhood retinal dystrophies characterized by vision loss, nystagmus, and severe retinal dysfunction. Patients usually present at birth with profound vision loss and pendular nystagmus. Electroretinogram (ERG) responses are usually nonrecordable. Other clinical findings may include high hypermetropia, photodysphoria, oculodigital sign, keratoconus, cataracts, and a variable appearance to the fundus (summary by <a href="#4" class="mim-tip-reference" title="Chung, D. C., Traboulsi, E. I. <strong>Leber congenital amaurosis: clinical correlations with genotypes, gene therapy trials update, and future directions.</strong> J. AAPOS 13: 587-592, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20006823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20006823</a>] [<a href="https://doi.org/10.1016/j.jaapos.2009.10.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20006823">Chung and Traboulsi, 2009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20006823" 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>For a general description and a discussion of genetic heterogeneity of LCA, see <a href="/entry/204000">204000</a>.</p>
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<p><a href="#14" class="mim-tip-reference" title="Waardenburg, P. J., Schappert-Kimmijser, J. <strong>On various recessive biotypes of Leber's congenital amaurosis.</strong> Acta Ophthal. 41: 317-320, 1963.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14047474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14047474</a>] [<a href="https://doi.org/10.1111/j.1755-3768.1963.tb02444.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14047474">Waardenburg and Schappert-Kimmijser (1963)</a> published a pedigree that showed all normal children from 2 affected parents with Leber congenital amaurosis (LCA). The mother had 2 affected sisters and the father was the product of a first-cousin marriage. Keratoconus (or keratoglobus), a frequent feature of this condition, was not present in either parent but was found in one of the mother's affected sisters. This condition is, of course, not to be confused with Leber optic atrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14047474" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Chung, D. C., Traboulsi, E. I. <strong>Leber congenital amaurosis: clinical correlations with genotypes, gene therapy trials update, and future directions.</strong> J. AAPOS 13: 587-592, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20006823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20006823</a>] [<a href="https://doi.org/10.1016/j.jaapos.2009.10.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20006823">Chung and Traboulsi (2009)</a> noted that LCA2 is distinguished by moderate visual impairment at infancy that progresses to total blindness by mid to late adulthood. One of the unique qualities of LCA2 is that, even with profound early visual impairment, retinal cells are relatively preserved. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20006823" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Morimura, H., Fishman, G. A., Grover, S. A., Fulton, A. B., Berson, E. L., Dryja, T. P. <strong>Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or Leber congenital amaurosis.</strong> Proc. Nat. Acad. Sci. 95: 3088-3093, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9501220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9501220</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9501220[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.95.6.3088" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9501220">Morimura et al. (1998)</a> summarized the clinical criteria distinguishing retinitis pigmentosa (RP) from LCA. RP is the diagnosis given to patients with photoreceptor degeneration who have good central vision within the first decade of life. The diagnosis of LCA is given to patients who are born blind or who lose vision within a few months after birth. Both diagnostic entities feature attenuated retinal vessels and a variable amount of retinal pigmentation in older patients and a reduced or nondetectable electroretinogram (ERG) at all ages. <a href="#11" class="mim-tip-reference" title="Morimura, H., Fishman, G. A., Grover, S. A., Fulton, A. B., Berson, E. L., Dryja, T. P. <strong>Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or Leber congenital amaurosis.</strong> Proc. Nat. Acad. Sci. 95: 3088-3093, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9501220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9501220</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9501220[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.95.6.3088" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9501220">Morimura et al. (1998)</a> noted that there was no universally accepted diagnostic term for those patients with retinal degeneration who lose useful (ambulatory) vision during the first few years of life, with ophthalmologists considering such cases as either LCA or severe RP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9501220" 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="#16" class="mim-tip-reference" title="Yzer, S., van den Born, L. I., Schuil, J., Kroes, H. Y., van Genderen, M. M., Boonstra, F. N., van den Helm, B., Brunner, H. G., Koenekoop, R. K., Cremers, F. P. M. <strong>A tyr368his RPE65 founder mutation is associated with variable expression and progression of early onset retinal dystrophy in 10 families of a genetically isolated population. (Letter)</strong> J. Med. Genet. 40: 709-713, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12960219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12960219</a>] [<a href="https://doi.org/10.1136/jmg.40.9.709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12960219">Yzer et al. (2003)</a> studied 14 patients with early-onset retinal dystrophy from 10 related Dutch families from a genetically isolated population living on a former island in the Netherlands, previously reported by <a href="#13" class="mim-tip-reference" title="Schappert-Kimmijser, J., Henkes, H. E., Van den Bosch, J. <strong>Amaurosis congenita (Leber).</strong> AMA Arch. Ophthal. 61: 211-218, 1959.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13616783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13616783</a>] [<a href="https://doi.org/10.1001/archopht.1959.00940090213003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="13616783">Schappert-Kimmijser et al. (1959)</a>, as having a high incidence of LCA. None of the 14 newborns followed objects or made eye contact, leading their parents to suspect visual impairment within the first 3 months of life. All had night blindness, and none had photophobia, and all but 2 children showed early-onset nystagmus or developed nystagmus before 6 years of age. A wide range of visual acuities was observed at first examination, and at follow-up visual acuity had remained relatively stable in 9 patients, whereas in 4 it had deteriorated. In the 7 patients in whom color vision testing could be performed, color vision was severely disturbed and tended to the tritan axis (see <a href="/entry/190900">190900</a>). Visual field defects were slightly progressive, but peripheral fields remained relatively stable in 10 patients. ERGs were performed by 3 years of age in 12 patients, of whom 7 had no responses detected (5 within the first year of life); in 4 patients, severely reduced photopic responses were measured with absent scotopic responses, and in only 1 patient were both scotopic and photopic responses measured. <a href="#16" class="mim-tip-reference" title="Yzer, S., van den Born, L. I., Schuil, J., Kroes, H. Y., van Genderen, M. M., Boonstra, F. N., van den Helm, B., Brunner, H. G., Koenekoop, R. K., Cremers, F. P. M. <strong>A tyr368his RPE65 founder mutation is associated with variable expression and progression of early onset retinal dystrophy in 10 families of a genetically isolated population. (Letter)</strong> J. Med. Genet. 40: 709-713, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12960219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12960219</a>] [<a href="https://doi.org/10.1136/jmg.40.9.709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12960219">Yzer et al. (2003)</a> noted that the age of onset of the retinal dystrophy in these patients suggested LCA, but that several characteristics, including visual acuity, visual fields, and night blindness, led them to classify the phenotype as an early-onset severe retinal dystrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12960219+13616783" 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="#2" class="mim-tip-reference" title="Al-Khayer, K., Hagstrom, S., Pauer, G., Zegarra, H., Sears, J., Traboulsi, E. I. <strong>Thirty-year follow-up of a patient with Leber congenital amaurosis and novel RPE65 mutations.</strong> Am. J. Ophthal. 137: 375-377, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14962443/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14962443</a>] [<a href="https://doi.org/10.1016/S0002-9394(03)00913-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14962443">Al-Khayer et al. (2004)</a> reported a 35-year-old patient with LCA due to compound heterozygosity for mutations in the RPE65 gene. She had severe visual deficits and had presented in infancy with night blindness, nystagmus, and absent rod and cone electroretinograms. Although in early childhood her visual acuity was 20/60 in both eyes and color recognition was normal, at age 35 years her acuity had declined to 2/200 in the right eye and 1/200 in the left eye. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14962443" 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 LCA2 in the family reported by <a href="#10" class="mim-tip-reference" title="Marlhens, F., Bareil, C., Griffoin, J.-M., Zrenner, E., Amalric, P., Eliaou, C., Liu, S.-Y., Harris, E., Redmond, T. M., Arnaud, B., Claustres, M., Hamel, C. P. <strong>Mutations in RPE65 cause Leber's congenital amaurosis. (Letter)</strong> Nature Genet. 17: 139-141, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9326927/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9326927</a>] [<a href="https://doi.org/10.1038/ng1097-139" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9326927">Marlhens et al. (1997)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9326927" 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="#16" class="mim-tip-reference" title="Yzer, S., van den Born, L. I., Schuil, J., Kroes, H. Y., van Genderen, M. M., Boonstra, F. N., van den Helm, B., Brunner, H. G., Koenekoop, R. K., Cremers, F. P. M. <strong>A tyr368his RPE65 founder mutation is associated with variable expression and progression of early onset retinal dystrophy in 10 families of a genetically isolated population. (Letter)</strong> J. Med. Genet. 40: 709-713, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12960219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12960219</a>] [<a href="https://doi.org/10.1136/jmg.40.9.709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12960219">Yzer et al. (2003)</a> performed linkage analysis in 10 related Dutch families with early-onset severe retinal dystrophy and identified homozygosity for the 'b' allele of marker D1S2803 in all but 1 affected individual from 8 informative families. Analysis of marker D1S2895, located 3 cM proximal to the RPE65 gene (<a href="/entry/180069">180069</a>), also revealed homozygosity of 1 allele in 5 of 8 informative families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12960219" 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 existence of at least 2 genetically distinct forms of Leber congenital amaurosis was established by the demonstration of <a href="#10" class="mim-tip-reference" title="Marlhens, F., Bareil, C., Griffoin, J.-M., Zrenner, E., Amalric, P., Eliaou, C., Liu, S.-Y., Harris, E., Redmond, T. M., Arnaud, B., Claustres, M., Hamel, C. P. <strong>Mutations in RPE65 cause Leber's congenital amaurosis. (Letter)</strong> Nature Genet. 17: 139-141, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9326927/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9326927</a>] [<a href="https://doi.org/10.1038/ng1097-139" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9326927">Marlhens et al. (1997)</a> that the disorder can be caused not only by mutations in the gene for retinal guanylate cyclase (<a href="/entry/600179">600179</a>), but also by mutations in the RPE65 gene. In 2 sibs with LCA2, they identified compound heterozygosity for mutations in the RPE65 gene: a 1-bp deletion (<a href="/entry/180069#0001">180069.0001</a>) and a nonsense mutation (<a href="/entry/180069#0002">180069.0002</a>) inherited from the mother and father, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9326927" 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 13 patients with early-onset severe retinal dystrophy from 9 related Dutch families from a genetically isolated population living on a former island, <a href="#16" class="mim-tip-reference" title="Yzer, S., van den Born, L. I., Schuil, J., Kroes, H. Y., van Genderen, M. M., Boonstra, F. N., van den Helm, B., Brunner, H. G., Koenekoop, R. K., Cremers, F. P. M. <strong>A tyr368his RPE65 founder mutation is associated with variable expression and progression of early onset retinal dystrophy in 10 families of a genetically isolated population. (Letter)</strong> J. Med. Genet. 40: 709-713, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12960219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12960219</a>] [<a href="https://doi.org/10.1136/jmg.40.9.709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12960219">Yzer et al. (2003)</a> analyzed the RPE65 gene and identified homozygosity for a missense mutation (Y368H; <a href="/entry/180069#0009">180069.0009</a>). A patient from another related family was found to be compound heterozygous for Y368H and a splice site mutation (<a href="/entry/180069#0010">180069.0010</a>). Among 25 unaffected sibs tested, 17 were heterozygous for the Y368H mutation, and 8 did not carry the mutation. The Y368H mutation was found in 3 (3.1%) of 96 unrelated controls from the same isolated Dutch population. <a href="#16" class="mim-tip-reference" title="Yzer, S., van den Born, L. I., Schuil, J., Kroes, H. Y., van Genderen, M. M., Boonstra, F. N., van den Helm, B., Brunner, H. G., Koenekoop, R. K., Cremers, F. P. M. <strong>A tyr368his RPE65 founder mutation is associated with variable expression and progression of early onset retinal dystrophy in 10 families of a genetically isolated population. (Letter)</strong> J. Med. Genet. 40: 709-713, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12960219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12960219</a>] [<a href="https://doi.org/10.1136/jmg.40.9.709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12960219">Yzer et al. (2003)</a> noted that in a study of the same genetically isolated Dutch population, <a href="#13" class="mim-tip-reference" title="Schappert-Kimmijser, J., Henkes, H. E., Van den Bosch, J. <strong>Amaurosis congenita (Leber).</strong> AMA Arch. Ophthal. 61: 211-218, 1959.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13616783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13616783</a>] [<a href="https://doi.org/10.1001/archopht.1959.00940090213003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="13616783">Schappert-Kimmijser et al. (1959)</a> ascertained 13 LCA patients in 8 families; <a href="#16" class="mim-tip-reference" title="Yzer, S., van den Born, L. I., Schuil, J., Kroes, H. Y., van Genderen, M. M., Boonstra, F. N., van den Helm, B., Brunner, H. G., Koenekoop, R. K., Cremers, F. P. M. <strong>A tyr368his RPE65 founder mutation is associated with variable expression and progression of early onset retinal dystrophy in 10 families of a genetically isolated population. (Letter)</strong> J. Med. Genet. 40: 709-713, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12960219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12960219</a>] [<a href="https://doi.org/10.1136/jmg.40.9.709" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12960219">Yzer et al. (2003)</a> predicted that most if not all of those patients carried the Y368H founder mutation. The Y368H founder mutation was not detected in 86 LCA patients from a different white population or in 94 controls from the Netherlands, but analysis of 75 Dutch patients with autosomal recessive or isolated retinitis pigmentosa revealed the presence of the mutation in heterozygosity in 1 Dutch patient with RP and early-onset vision loss. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12960219+13616783" 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="#2" class="mim-tip-reference" title="Al-Khayer, K., Hagstrom, S., Pauer, G., Zegarra, H., Sears, J., Traboulsi, E. I. <strong>Thirty-year follow-up of a patient with Leber congenital amaurosis and novel RPE65 mutations.</strong> Am. J. Ophthal. 137: 375-377, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14962443/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14962443</a>] [<a href="https://doi.org/10.1016/S0002-9394(03)00913-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14962443">Al-Khayer et al. (2004)</a> identified compound heterozygosity for mutations in the RPE65 gene (<a href="/entry/180069#0011">180069.0011</a> and <a href="/entry/180069#0012">180069.0012</a>) in a 35-year-old woman with LCA2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14962443" 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="#7" class="mim-tip-reference" title="Hauswirth, W. W., Aleman, T. S., Kaushal, S., Cideciyan, A. V., Schwartz, S. B., Wang, L., Conlon, T. J., Boye, S. L., Flotte, T. R., Byrne, B. J., Jacobson, S. G. <strong>Treatment of Leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial.</strong> Hum. Gene Ther. 19: 979-990, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18774912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18774912</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18774912[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1089/hum.2008.107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18774912">Hauswirth et al. (2008)</a> reported results at 90 days after RPE65 gene therapy in 3 young adults with LCA2, 2 of whom were homozygous and 1 compound heterozygous for mutations that had been previously reported to be associated with LCA and for which little or no RPE65 isomerase activity had been demonstrated by in vitro studies. The eye with worse visual function received vector administration in each case. Post-treatment visual acuity was not significantly different from baseline. All patients reported increased visual sensitivity in the study eye, especially noticeable under reduced ambient light conditions; dark-adapted full-field sensitivity testing showed significant increases compared to the control eye (p less than 0.001). <a href="#7" class="mim-tip-reference" title="Hauswirth, W. W., Aleman, T. S., Kaushal, S., Cideciyan, A. V., Schwartz, S. B., Wang, L., Conlon, T. J., Boye, S. L., Flotte, T. R., Byrne, B. J., Jacobson, S. G. <strong>Treatment of Leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial.</strong> Hum. Gene Ther. 19: 979-990, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18774912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18774912</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18774912[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1089/hum.2008.107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18774912">Hauswirth et al. (2008)</a> reviewed the results of 2 concurrent RPE65 gene therapy trials (<a href="#3" class="mim-tip-reference" title="Bainbridge, J. W. B., Smith, A. J., Barker, S. S., Robbie, S., Henderson, R., Balaggan, K., Viswanathan, A., Holder, G. E., Stockman, A., Tyler, N., Petersen-Jones, S., Bhattacharya, S. S., Thrasher, A. J., Fitzke, F. W., Carter, B. J., Rubin, G. S., Moore, A. T., Ali, R. R. <strong>Effect of gene therapy on visual function in Leber's congenital amaurosis.</strong> New Eng. J. Med. 358: 2231-2239, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18441371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18441371</a>] [<a href="https://doi.org/10.1056/NEJMoa0802268" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18441371">Bainbridge et al., 2008</a>; <a href="#9" class="mim-tip-reference" title="Maguire, A. M., Simonelli, F., Pierce, E. A., Pugh, E. N., Jr., Mingozzi, F., Bennicelli, J., Banfi, S., Marshall, K. A., Testa, F., Surace, E. M., Rossi, S., Lyubarsky, A., and 20 others. <strong>Safety and efficacy of gene transfer for Leber's congenital amaurosis.</strong> New Eng. J. Med. 358: 2240-2248, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18441370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18441370</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18441370[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1056/NEJMoa0802315" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18441370">Maguire et al., 2008</a>), but noted that outcomes were difficult to compare due to differences in technique among the 3 studies, including vector titer, area of RPE exposed to vector, and regulatory elements used to control expression of the human RPE65 cDNA, as well as large differences in visual function at baseline in each trial. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18441370+18441371+18774912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Cideciyan, A. V., Aleman, T. S., Boye, S. L., Schwartz, S. B., Kaushal, S., Roman, A. J., Pang, J., Sumaroka, A., Windsor, E. A. M., Wilson, J. M., Flotte, T. R., Fishman, G. A., Heon, E., Stone, E. M., Byrne, B. J., Jacobson, S. G., Hauswirth, W. W. <strong>Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics.</strong> Proc. Nat. Acad. Sci. 105: 15112-15117, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18809924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18809924</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18809924[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0807027105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18809924">Cideciyan et al. (2008)</a> analyzed rod and cone kinetics in the 3 LCA2 patients reported by <a href="#7" class="mim-tip-reference" title="Hauswirth, W. W., Aleman, T. S., Kaushal, S., Cideciyan, A. V., Schwartz, S. B., Wang, L., Conlon, T. J., Boye, S. L., Flotte, T. R., Byrne, B. J., Jacobson, S. G. <strong>Treatment of Leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial.</strong> Hum. Gene Ther. 19: 979-990, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18774912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18774912</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18774912[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1089/hum.2008.107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18774912">Hauswirth et al. (2008)</a> who had undergone RPE65 gene therapy. Both cone- and rod-photoreceptor-based vision could be demonstrated in treated areas, with increases up to 50-fold for cones and up to 63,000-fold for rods. Noting that visual loss in LCA2 is due to a combination of biochemical blockade of the retinoid cycle and degeneration of retinal photoreceptors, <a href="#5" class="mim-tip-reference" title="Cideciyan, A. V., Aleman, T. S., Boye, S. L., Schwartz, S. B., Kaushal, S., Roman, A. J., Pang, J., Sumaroka, A., Windsor, E. A. M., Wilson, J. M., Flotte, T. R., Fishman, G. A., Heon, E., Stone, E. M., Byrne, B. J., Jacobson, S. G., Hauswirth, W. W. <strong>Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics.</strong> Proc. Nat. Acad. Sci. 105: 15112-15117, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18809924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18809924</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18809924[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0807027105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18809924">Cideciyan et al. (2008)</a> related the degree of light sensitivity to the level of remaining photoreceptors within the treatment area, and found that the intervention could overcome nearly all of the loss of light sensitivity resulting from the biochemical blockade. The reconstituted retinoid cycle was not completely normal, however: although cone-sensitivity recovery time was rapid, resensitization kinetics of the newly treated rods were remarkably slow and required 8 hours or more to reach full sensitivity, compared with less than 1 hour in normal eyes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18774912+18809924" 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="Cideciyan, A. V., Hauswirth, W. W., Aleman, T. S., Kaushal, S., Schwartz, S. B., Boye, S. L., Windsor, E. A. M., Conlon, T. J., Sumaroka, A., Roman, A. J., Byrne, B. J., Jacobson, S. G. <strong>Vision 1 year after gene therapy for Leber's congenital amaurosis. (Letter)</strong> New Eng. J. Med. 361: 725-727, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19675341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19675341</a>] [<a href="https://doi.org/10.1056/NEJMc0903652" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19675341">Cideciyan et al. (2009)</a> provided follow-up on 1 of the patients previously studied by <a href="#7" class="mim-tip-reference" title="Hauswirth, W. W., Aleman, T. S., Kaushal, S., Cideciyan, A. V., Schwartz, S. B., Wang, L., Conlon, T. J., Boye, S. L., Flotte, T. R., Byrne, B. J., Jacobson, S. G. <strong>Treatment of Leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial.</strong> Hum. Gene Ther. 19: 979-990, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18774912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18774912</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18774912[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1089/hum.2008.107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18774912">Hauswirth et al. (2008)</a> who, 12 months after RPE65 gene therapy for LCA2, reported perception of the lowest luminance target for the first time, which was found to be accompanied by a distinct shift in fixation into the treated superotemporal retina. Further examination revealed that foveal sensitivities in her 2 eyes were similar, but the superotemporal region of the treated eye was remarkably different from the cone blindness in the comparable region of the untreated eye. <a href="#6" class="mim-tip-reference" title="Cideciyan, A. V., Hauswirth, W. W., Aleman, T. S., Kaushal, S., Schwartz, S. B., Boye, S. L., Windsor, E. A. M., Conlon, T. J., Sumaroka, A., Roman, A. J., Byrne, B. J., Jacobson, S. G. <strong>Vision 1 year after gene therapy for Leber's congenital amaurosis. (Letter)</strong> New Eng. J. Med. 361: 725-727, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19675341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19675341</a>] [<a href="https://doi.org/10.1056/NEJMc0903652" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19675341">Cideciyan et al. (2009)</a> concluded that the change in fixation was driven by treatment-created extrafoveal cone vision with better sensitivity and greater expanse than the untreated foveal region, suggesting the slow development of a 'pseudo-fovea' and an underlying experience-dependent plasticity of the adult visual system. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19675341+18774912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Maguire, A. M., High, K. A., Auricchio, A., Wright, J. F., Pierce, E. A., Testa, F., Mingozzi, F., Bennicelli, J. L., Ying, G., Rossi, S., Fulton, A., Marshall, K. A., and 21 others. <strong>Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial.</strong> Lancet 374: 1597-1605, 2009. Note: Erratum: Lancet 375: 30 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19854499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19854499</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19854499[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/S0140-6736(09)61836-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19854499">Maguire et al. (2009)</a> assessed the retinal and visual function in 12 patients aged 8 to 44 years with RPE65-associated Leber congenital amaurosis who had received 1 subretinal injection of adeno-associated virus (AAV) containing the RPE65 gene in the worse eye at low (1.5 x 10(10) vector genomes), medium (4.8 x 10(10) vector genomes), or high dose (1.5 x 10(11) vector genomes) for up to 2 years. Patients had at least 2 log unit increase in pupillary light responses, and an 8-year-old child had nearly the same level of light sensitivity as that in age-matched normal-sighted individuals. The greatest improvement was noted in children, all of whom gained ambulatory vision. Gene therapy was well tolerated and all patients showed sustained improvement in subjective and objective measurements of vision. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19854499" 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="#1" class="mim-tip-reference" title="Aguirre, G. D., Baldwin, V., Pearce-Kelling, S., Narfstrom, K., Ray, K., Acland, G. M. <strong>Congenital stationary night blindness in the dog: common mutation in the RPE65 gene indicates founder effect.</strong> Molec. Vision 4: 23, 1998. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9808841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9808841</a>]" pmid="9808841">Aguirre et al. (1998)</a> described a 4-bp deletion in the RPE65 gene in a form of retinal dystrophy in dogs of the Swedish Briard breed. The disorder was initially described by <a href="#12" class="mim-tip-reference" title="Narfstrom, K., Wrigstad, A., Nilsson, S. E. <strong>The Briard dog: a new animal model of congenital stationary night blindness.</strong> Brit. J. Ophthal. 73: 750-756, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2804031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2804031</a>] [<a href="https://doi.org/10.1136/bjo.73.9.750" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2804031">Narfstrom et al. (1989)</a> as a stationary disorder analogous to human congenital stationary night blindness (CSNB). The disorder was later described as having a progressive component and was termed hereditary retinal dystrophy (<a href="#15" class="mim-tip-reference" title="Wrigstad, A., Narfstrom, K., Nilsson, S. E. <strong>Slowly progressive changes of the retina and retinal pigment epithelium in Briard dogs with hereditary retinal dystrophy: a morphological study.</strong> Doc. Ophthal. 87: 337-354, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7851218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7851218</a>] [<a href="https://doi.org/10.1007/BF01203343" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7851218">Wrigstad et al., 1994</a>). <a href="#1" class="mim-tip-reference" title="Aguirre, G. D., Baldwin, V., Pearce-Kelling, S., Narfstrom, K., Ray, K., Acland, G. M. <strong>Congenital stationary night blindness in the dog: common mutation in the RPE65 gene indicates founder effect.</strong> Molec. Vision 4: 23, 1998. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9808841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9808841</a>]" pmid="9808841">Aguirre et al. (1998)</a> studied 10 Briard dogs affected with what has been called CSNB in the U.S. The dogs originated from stock in the U.S., Canada, and France. Identification of the same mutation in all of these dogs suggested a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9808841+2804031+7851218" 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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Aguirre, G. D., Baldwin, V., Pearce-Kelling, S., Narfstrom, K., Ray, K., Acland, G. M.
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<strong>Congenital stationary night blindness in the dog: common mutation in the RPE65 gene indicates founder effect.</strong>
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Molec. Vision 4: 23, 1998. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9808841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9808841</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9808841" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Al-Khayer, K., Hagstrom, S., Pauer, G., Zegarra, H., Sears, J., Traboulsi, E. I.
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<strong>Thirty-year follow-up of a patient with Leber congenital amaurosis and novel RPE65 mutations.</strong>
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Am. J. Ophthal. 137: 375-377, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14962443/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14962443</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14962443" 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/S0002-9394(03)00913-9" target="_blank">Full Text</a>]
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Bainbridge, J. W. B., Smith, A. J., Barker, S. S., Robbie, S., Henderson, R., Balaggan, K., Viswanathan, A., Holder, G. E., Stockman, A., Tyler, N., Petersen-Jones, S., Bhattacharya, S. S., Thrasher, A. J., Fitzke, F. W., Carter, B. J., Rubin, G. S., Moore, A. T., Ali, R. R.
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<strong>Effect of gene therapy on visual function in Leber's congenital amaurosis.</strong>
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New Eng. J. Med. 358: 2231-2239, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18441371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18441371</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18441371" 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/NEJMoa0802268" target="_blank">Full Text</a>]
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Chung, D. C., Traboulsi, E. I.
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<strong>Leber congenital amaurosis: clinical correlations with genotypes, gene therapy trials update, and future directions.</strong>
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J. AAPOS 13: 587-592, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20006823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20006823</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20006823" 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/j.jaapos.2009.10.004" target="_blank">Full Text</a>]
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Cideciyan, A. V., Aleman, T. S., Boye, S. L., Schwartz, S. B., Kaushal, S., Roman, A. J., Pang, J., Sumaroka, A., Windsor, E. A. M., Wilson, J. M., Flotte, T. R., Fishman, G. A., Heon, E., Stone, E. M., Byrne, B. J., Jacobson, S. G., Hauswirth, W. W.
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<strong>Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics.</strong>
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Proc. Nat. Acad. Sci. 105: 15112-15117, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18809924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18809924</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18809924[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18809924" 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.0807027105" target="_blank">Full Text</a>]
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Cideciyan, A. V., Hauswirth, W. W., Aleman, T. S., Kaushal, S., Schwartz, S. B., Boye, S. L., Windsor, E. A. M., Conlon, T. J., Sumaroka, A., Roman, A. J., Byrne, B. J., Jacobson, S. G.
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<strong>Vision 1 year after gene therapy for Leber's congenital amaurosis. (Letter)</strong>
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New Eng. J. Med. 361: 725-727, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19675341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19675341</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19675341" 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/NEJMc0903652" target="_blank">Full Text</a>]
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Hauswirth, W. W., Aleman, T. S., Kaushal, S., Cideciyan, A. V., Schwartz, S. B., Wang, L., Conlon, T. J., Boye, S. L., Flotte, T. R., Byrne, B. J., Jacobson, S. G.
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<strong>Treatment of Leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial.</strong>
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Hum. Gene Ther. 19: 979-990, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18774912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18774912</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18774912[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18774912" 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/10.1089/hum.2008.107" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Maguire2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Maguire, A. M., High, K. A., Auricchio, A., Wright, J. F., Pierce, E. A., Testa, F., Mingozzi, F., Bennicelli, J. L., Ying, G., Rossi, S., Fulton, A., Marshall, K. A., and 21 others.
|
|
<strong>Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial.</strong>
|
|
Lancet 374: 1597-1605, 2009. Note: Erratum: Lancet 375: 30 only, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19854499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19854499</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19854499[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19854499" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/S0140-6736(09)61836-5" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Maguire2008" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Maguire, A. M., Simonelli, F., Pierce, E. A., Pugh, E. N., Jr., Mingozzi, F., Bennicelli, J., Banfi, S., Marshall, K. A., Testa, F., Surace, E. M., Rossi, S., Lyubarsky, A., and 20 others.
|
|
<strong>Safety and efficacy of gene transfer for Leber's congenital amaurosis.</strong>
|
|
New Eng. J. Med. 358: 2240-2248, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18441370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18441370</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18441370[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18441370" 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/NEJMoa0802315" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Marlhens1997" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Marlhens, F., Bareil, C., Griffoin, J.-M., Zrenner, E., Amalric, P., Eliaou, C., Liu, S.-Y., Harris, E., Redmond, T. M., Arnaud, B., Claustres, M., Hamel, C. P.
|
|
<strong>Mutations in RPE65 cause Leber's congenital amaurosis. (Letter)</strong>
|
|
Nature Genet. 17: 139-141, 1997.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9326927/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9326927</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9326927" 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/ng1097-139" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Morimura1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Morimura, H., Fishman, G. A., Grover, S. A., Fulton, A. B., Berson, E. L., Dryja, T. P.
|
|
<strong>Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or Leber congenital amaurosis.</strong>
|
|
Proc. Nat. Acad. Sci. 95: 3088-3093, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9501220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9501220</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9501220[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9501220" 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.95.6.3088" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Narfstrom1989" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Narfstrom, K., Wrigstad, A., Nilsson, S. E.
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<strong>The Briard dog: a new animal model of congenital stationary night blindness.</strong>
|
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Brit. J. Ophthal. 73: 750-756, 1989.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2804031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2804031</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2804031" 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/10.1136/bjo.73.9.750" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Schappert-Kimmijser1959" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Schappert-Kimmijser, J., Henkes, H. E., Van den Bosch, J.
|
|
<strong>Amaurosis congenita (Leber).</strong>
|
|
AMA Arch. Ophthal. 61: 211-218, 1959.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13616783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13616783</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13616783" 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/10.1001/archopht.1959.00940090213003" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Waardenburg1963" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Waardenburg, P. J., Schappert-Kimmijser, J.
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<strong>On various recessive biotypes of Leber's congenital amaurosis.</strong>
|
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Acta Ophthal. 41: 317-320, 1963.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14047474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14047474</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14047474" 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/10.1111/j.1755-3768.1963.tb02444.x" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="Wrigstad1994" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wrigstad, A., Narfstrom, K., Nilsson, S. E.
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<strong>Slowly progressive changes of the retina and retinal pigment epithelium in Briard dogs with hereditary retinal dystrophy: a morphological study.</strong>
|
|
Doc. Ophthal. 87: 337-354, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7851218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7851218</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7851218" 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/10.1007/BF01203343" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="16" class="mim-anchor"></a>
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<a id="Yzer2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yzer, S., van den Born, L. I., Schuil, J., Kroes, H. Y., van Genderen, M. M., Boonstra, F. N., van den Helm, B., Brunner, H. G., Koenekoop, R. K., Cremers, F. P. M.
|
|
<strong>A tyr368his RPE65 founder mutation is associated with variable expression and progression of early onset retinal dystrophy in 10 families of a genetically isolated population. (Letter)</strong>
|
|
J. Med. Genet. 40: 709-713, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12960219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12960219</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12960219" 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/10.1136/jmg.40.9.709" target="_blank">Full Text</a>]
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</p>
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</div>
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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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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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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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Marla J. F. O'Neill - updated : 4/6/2011
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 3/19/2010<br>Marla J. F. O'Neill - updated : 3/1/2010<br>Marla J. F. O'Neill - updated : 8/20/2009<br>Victor A. McKusick - updated : 11/10/1998<br>Ada Hamosh - updated : 11/9/1998<br>Victor A. McKusick - updated : 9/26/1997
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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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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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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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Victor A. McKusick : 6/3/1986
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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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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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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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alopez : 04/27/2023
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 02/24/2022<br>carol : 06/12/2019<br>carol : 12/08/2016<br>alopez : 11/26/2012<br>wwang : 5/13/2011<br>wwang : 4/15/2011<br>terry : 4/6/2011<br>terry : 3/30/2011<br>carol : 3/28/2011<br>alopez : 3/22/2010<br>terry : 3/19/2010<br>carol : 3/1/2010<br>wwang : 9/14/2009<br>wwang : 9/9/2009<br>terry : 8/20/2009<br>carol : 4/3/2009<br>tkritzer : 8/6/2004<br>carol : 10/15/1999<br>terry : 6/11/1999<br>carol : 11/18/1998<br>terry : 11/10/1998<br>alopez : 11/9/1998<br>carol : 4/24/1998<br>mark : 9/26/1997<br>terry : 9/22/1997<br>terry : 9/22/1997<br>mimadm : 11/12/1995<br>warfield : 3/7/1994<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>ddp : 10/26/1989<br>marie : 3/25/1988
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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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</div>
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</div>
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<div class="container visible-print-block">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>#</strong> 204100
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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LEBER CONGENITAL AMAUROSIS 2; LCA2
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</span>
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</h3>
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</div>
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<div>
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<br />
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</p>
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<div>
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<h4>
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<span class="mim-font">
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AMAUROSIS CONGENITA OF LEBER II
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</span>
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</h4>
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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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<p>
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<span class="mim-text-font">
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<strong>ORPHA:</strong> 65;
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<strong>DO:</strong> 0110016;
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</span>
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</p>
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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>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 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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1p31.3
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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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Leber congenital amaurosis 2
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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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204100
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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 recessive
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<td>
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<span class="mim-font">
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3
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</td>
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<td>
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<span class="mim-font">
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RPE65
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</td>
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<td>
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<span class="mim-font">
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180069
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</tr>
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</tbody>
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</table>
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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 of evidence that Leber congenital amaurosis-2 (LCA2) is caused by homozygous or compound heterozygous mutation in the RPE65 gene (180069) on chromosome 1p31.</p><p>Mutations in this gene also cause retinitis pigmentosa (RP20; 613794).</p>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</h4>
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<span class="mim-text-font">
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<p>Leber congenital amaurosis comprises a group of early-onset childhood retinal dystrophies characterized by vision loss, nystagmus, and severe retinal dysfunction. Patients usually present at birth with profound vision loss and pendular nystagmus. Electroretinogram (ERG) responses are usually nonrecordable. Other clinical findings may include high hypermetropia, photodysphoria, oculodigital sign, keratoconus, cataracts, and a variable appearance to the fundus (summary by Chung and Traboulsi, 2009). </p><p>For a general description and a discussion of genetic heterogeneity of LCA, see 204000.</p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Clinical Features</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>Waardenburg and Schappert-Kimmijser (1963) published a pedigree that showed all normal children from 2 affected parents with Leber congenital amaurosis (LCA). The mother had 2 affected sisters and the father was the product of a first-cousin marriage. Keratoconus (or keratoglobus), a frequent feature of this condition, was not present in either parent but was found in one of the mother's affected sisters. This condition is, of course, not to be confused with Leber optic atrophy. </p><p>Chung and Traboulsi (2009) noted that LCA2 is distinguished by moderate visual impairment at infancy that progresses to total blindness by mid to late adulthood. One of the unique qualities of LCA2 is that, even with profound early visual impairment, retinal cells are relatively preserved. </p><p>Morimura et al. (1998) summarized the clinical criteria distinguishing retinitis pigmentosa (RP) from LCA. RP is the diagnosis given to patients with photoreceptor degeneration who have good central vision within the first decade of life. The diagnosis of LCA is given to patients who are born blind or who lose vision within a few months after birth. Both diagnostic entities feature attenuated retinal vessels and a variable amount of retinal pigmentation in older patients and a reduced or nondetectable electroretinogram (ERG) at all ages. Morimura et al. (1998) noted that there was no universally accepted diagnostic term for those patients with retinal degeneration who lose useful (ambulatory) vision during the first few years of life, with ophthalmologists considering such cases as either LCA or severe RP. </p><p>Yzer et al. (2003) studied 14 patients with early-onset retinal dystrophy from 10 related Dutch families from a genetically isolated population living on a former island in the Netherlands, previously reported by Schappert-Kimmijser et al. (1959), as having a high incidence of LCA. None of the 14 newborns followed objects or made eye contact, leading their parents to suspect visual impairment within the first 3 months of life. All had night blindness, and none had photophobia, and all but 2 children showed early-onset nystagmus or developed nystagmus before 6 years of age. A wide range of visual acuities was observed at first examination, and at follow-up visual acuity had remained relatively stable in 9 patients, whereas in 4 it had deteriorated. In the 7 patients in whom color vision testing could be performed, color vision was severely disturbed and tended to the tritan axis (see 190900). Visual field defects were slightly progressive, but peripheral fields remained relatively stable in 10 patients. ERGs were performed by 3 years of age in 12 patients, of whom 7 had no responses detected (5 within the first year of life); in 4 patients, severely reduced photopic responses were measured with absent scotopic responses, and in only 1 patient were both scotopic and photopic responses measured. Yzer et al. (2003) noted that the age of onset of the retinal dystrophy in these patients suggested LCA, but that several characteristics, including visual acuity, visual fields, and night blindness, led them to classify the phenotype as an early-onset severe retinal dystrophy. </p><p>Al-Khayer et al. (2004) reported a 35-year-old patient with LCA due to compound heterozygosity for mutations in the RPE65 gene. She had severe visual deficits and had presented in infancy with night blindness, nystagmus, and absent rod and cone electroretinograms. Although in early childhood her visual acuity was 20/60 in both eyes and color recognition was normal, at age 35 years her acuity had declined to 2/200 in the right eye and 1/200 in the left eye. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Inheritance</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>The transmission pattern of LCA2 in the family reported by Marlhens et al. (1997) was consistent with autosomal recessive inheritance. </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>Mapping</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>Yzer et al. (2003) performed linkage analysis in 10 related Dutch families with early-onset severe retinal dystrophy and identified homozygosity for the 'b' allele of marker D1S2803 in all but 1 affected individual from 8 informative families. Analysis of marker D1S2895, located 3 cM proximal to the RPE65 gene (180069), also revealed homozygosity of 1 allele in 5 of 8 informative families. </p>
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</span>
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<div>
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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>Molecular Genetics</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>The existence of at least 2 genetically distinct forms of Leber congenital amaurosis was established by the demonstration of Marlhens et al. (1997) that the disorder can be caused not only by mutations in the gene for retinal guanylate cyclase (600179), but also by mutations in the RPE65 gene. In 2 sibs with LCA2, they identified compound heterozygosity for mutations in the RPE65 gene: a 1-bp deletion (180069.0001) and a nonsense mutation (180069.0002) inherited from the mother and father, respectively. </p><p>In 13 patients with early-onset severe retinal dystrophy from 9 related Dutch families from a genetically isolated population living on a former island, Yzer et al. (2003) analyzed the RPE65 gene and identified homozygosity for a missense mutation (Y368H; 180069.0009). A patient from another related family was found to be compound heterozygous for Y368H and a splice site mutation (180069.0010). Among 25 unaffected sibs tested, 17 were heterozygous for the Y368H mutation, and 8 did not carry the mutation. The Y368H mutation was found in 3 (3.1%) of 96 unrelated controls from the same isolated Dutch population. Yzer et al. (2003) noted that in a study of the same genetically isolated Dutch population, Schappert-Kimmijser et al. (1959) ascertained 13 LCA patients in 8 families; Yzer et al. (2003) predicted that most if not all of those patients carried the Y368H founder mutation. The Y368H founder mutation was not detected in 86 LCA patients from a different white population or in 94 controls from the Netherlands, but analysis of 75 Dutch patients with autosomal recessive or isolated retinitis pigmentosa revealed the presence of the mutation in heterozygosity in 1 Dutch patient with RP and early-onset vision loss. </p><p>Al-Khayer et al. (2004) identified compound heterozygosity for mutations in the RPE65 gene (180069.0011 and 180069.0012) in a 35-year-old woman with LCA2. </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>Clinical Management</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><strong><em>Gene Therapy</em></strong></p><p>
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Hauswirth et al. (2008) reported results at 90 days after RPE65 gene therapy in 3 young adults with LCA2, 2 of whom were homozygous and 1 compound heterozygous for mutations that had been previously reported to be associated with LCA and for which little or no RPE65 isomerase activity had been demonstrated by in vitro studies. The eye with worse visual function received vector administration in each case. Post-treatment visual acuity was not significantly different from baseline. All patients reported increased visual sensitivity in the study eye, especially noticeable under reduced ambient light conditions; dark-adapted full-field sensitivity testing showed significant increases compared to the control eye (p less than 0.001). Hauswirth et al. (2008) reviewed the results of 2 concurrent RPE65 gene therapy trials (Bainbridge et al., 2008; Maguire et al., 2008), but noted that outcomes were difficult to compare due to differences in technique among the 3 studies, including vector titer, area of RPE exposed to vector, and regulatory elements used to control expression of the human RPE65 cDNA, as well as large differences in visual function at baseline in each trial. </p><p>Cideciyan et al. (2008) analyzed rod and cone kinetics in the 3 LCA2 patients reported by Hauswirth et al. (2008) who had undergone RPE65 gene therapy. Both cone- and rod-photoreceptor-based vision could be demonstrated in treated areas, with increases up to 50-fold for cones and up to 63,000-fold for rods. Noting that visual loss in LCA2 is due to a combination of biochemical blockade of the retinoid cycle and degeneration of retinal photoreceptors, Cideciyan et al. (2008) related the degree of light sensitivity to the level of remaining photoreceptors within the treatment area, and found that the intervention could overcome nearly all of the loss of light sensitivity resulting from the biochemical blockade. The reconstituted retinoid cycle was not completely normal, however: although cone-sensitivity recovery time was rapid, resensitization kinetics of the newly treated rods were remarkably slow and required 8 hours or more to reach full sensitivity, compared with less than 1 hour in normal eyes. </p><p>Cideciyan et al. (2009) provided follow-up on 1 of the patients previously studied by Hauswirth et al. (2008) who, 12 months after RPE65 gene therapy for LCA2, reported perception of the lowest luminance target for the first time, which was found to be accompanied by a distinct shift in fixation into the treated superotemporal retina. Further examination revealed that foveal sensitivities in her 2 eyes were similar, but the superotemporal region of the treated eye was remarkably different from the cone blindness in the comparable region of the untreated eye. Cideciyan et al. (2009) concluded that the change in fixation was driven by treatment-created extrafoveal cone vision with better sensitivity and greater expanse than the untreated foveal region, suggesting the slow development of a 'pseudo-fovea' and an underlying experience-dependent plasticity of the adult visual system. </p><p>Maguire et al. (2009) assessed the retinal and visual function in 12 patients aged 8 to 44 years with RPE65-associated Leber congenital amaurosis who had received 1 subretinal injection of adeno-associated virus (AAV) containing the RPE65 gene in the worse eye at low (1.5 x 10(10) vector genomes), medium (4.8 x 10(10) vector genomes), or high dose (1.5 x 10(11) vector genomes) for up to 2 years. Patients had at least 2 log unit increase in pupillary light responses, and an 8-year-old child had nearly the same level of light sensitivity as that in age-matched normal-sighted individuals. The greatest improvement was noted in children, all of whom gained ambulatory vision. Gene therapy was well tolerated and all patients showed sustained improvement in subjective and objective measurements of vision. </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>Animal Model</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>Aguirre et al. (1998) described a 4-bp deletion in the RPE65 gene in a form of retinal dystrophy in dogs of the Swedish Briard breed. The disorder was initially described by Narfstrom et al. (1989) as a stationary disorder analogous to human congenital stationary night blindness (CSNB). The disorder was later described as having a progressive component and was termed hereditary retinal dystrophy (Wrigstad et al., 1994). Aguirre et al. (1998) studied 10 Briard dogs affected with what has been called CSNB in the U.S. The dogs originated from stock in the U.S., Canada, and France. Identification of the same mutation in all of these dogs suggested a founder effect. </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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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Aguirre, G. D., Baldwin, V., Pearce-Kelling, S., Narfstrom, K., Ray, K., Acland, G. M.
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<strong>Congenital stationary night blindness in the dog: common mutation in the RPE65 gene indicates founder effect.</strong>
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Molec. Vision 4: 23, 1998. Note: Electronic Article.
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[PubMed: 9808841]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Al-Khayer, K., Hagstrom, S., Pauer, G., Zegarra, H., Sears, J., Traboulsi, E. I.
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<strong>Thirty-year follow-up of a patient with Leber congenital amaurosis and novel RPE65 mutations.</strong>
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Am. J. Ophthal. 137: 375-377, 2004.
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[PubMed: 14962443]
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[Full Text: https://doi.org/10.1016/S0002-9394(03)00913-9]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Bainbridge, J. W. B., Smith, A. J., Barker, S. S., Robbie, S., Henderson, R., Balaggan, K., Viswanathan, A., Holder, G. E., Stockman, A., Tyler, N., Petersen-Jones, S., Bhattacharya, S. S., Thrasher, A. J., Fitzke, F. W., Carter, B. J., Rubin, G. S., Moore, A. T., Ali, R. R.
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<strong>Effect of gene therapy on visual function in Leber's congenital amaurosis.</strong>
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New Eng. J. Med. 358: 2231-2239, 2008.
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[PubMed: 18441371]
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[Full Text: https://doi.org/10.1056/NEJMoa0802268]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Chung, D. C., Traboulsi, E. I.
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<strong>Leber congenital amaurosis: clinical correlations with genotypes, gene therapy trials update, and future directions.</strong>
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J. AAPOS 13: 587-592, 2009.
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[PubMed: 20006823]
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[Full Text: https://doi.org/10.1016/j.jaapos.2009.10.004]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Cideciyan, A. V., Aleman, T. S., Boye, S. L., Schwartz, S. B., Kaushal, S., Roman, A. J., Pang, J., Sumaroka, A., Windsor, E. A. M., Wilson, J. M., Flotte, T. R., Fishman, G. A., Heon, E., Stone, E. M., Byrne, B. J., Jacobson, S. G., Hauswirth, W. W.
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<strong>Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics.</strong>
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Proc. Nat. Acad. Sci. 105: 15112-15117, 2008.
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[PubMed: 18809924]
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[Full Text: https://doi.org/10.1073/pnas.0807027105]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Cideciyan, A. V., Hauswirth, W. W., Aleman, T. S., Kaushal, S., Schwartz, S. B., Boye, S. L., Windsor, E. A. M., Conlon, T. J., Sumaroka, A., Roman, A. J., Byrne, B. J., Jacobson, S. G.
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<strong>Vision 1 year after gene therapy for Leber's congenital amaurosis. (Letter)</strong>
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New Eng. J. Med. 361: 725-727, 2009.
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[PubMed: 19675341]
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[Full Text: https://doi.org/10.1056/NEJMc0903652]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Hauswirth, W. W., Aleman, T. S., Kaushal, S., Cideciyan, A. V., Schwartz, S. B., Wang, L., Conlon, T. J., Boye, S. L., Flotte, T. R., Byrne, B. J., Jacobson, S. G.
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<strong>Treatment of Leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial.</strong>
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Hum. Gene Ther. 19: 979-990, 2008.
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[PubMed: 18774912]
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[Full Text: https://doi.org/10.1089/hum.2008.107]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Maguire, A. M., High, K. A., Auricchio, A., Wright, J. F., Pierce, E. A., Testa, F., Mingozzi, F., Bennicelli, J. L., Ying, G., Rossi, S., Fulton, A., Marshall, K. A., and 21 others.
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<strong>Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial.</strong>
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Lancet 374: 1597-1605, 2009. Note: Erratum: Lancet 375: 30 only, 2010.
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[PubMed: 19854499]
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[Full Text: https://doi.org/10.1016/S0140-6736(09)61836-5]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Maguire, A. M., Simonelli, F., Pierce, E. A., Pugh, E. N., Jr., Mingozzi, F., Bennicelli, J., Banfi, S., Marshall, K. A., Testa, F., Surace, E. M., Rossi, S., Lyubarsky, A., and 20 others.
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<strong>Safety and efficacy of gene transfer for Leber's congenital amaurosis.</strong>
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New Eng. J. Med. 358: 2240-2248, 2008.
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[PubMed: 18441370]
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[Full Text: https://doi.org/10.1056/NEJMoa0802315]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Marlhens, F., Bareil, C., Griffoin, J.-M., Zrenner, E., Amalric, P., Eliaou, C., Liu, S.-Y., Harris, E., Redmond, T. M., Arnaud, B., Claustres, M., Hamel, C. P.
|
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<strong>Mutations in RPE65 cause Leber's congenital amaurosis. (Letter)</strong>
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Nature Genet. 17: 139-141, 1997.
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[PubMed: 9326927]
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[Full Text: https://doi.org/10.1038/ng1097-139]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Morimura, H., Fishman, G. A., Grover, S. A., Fulton, A. B., Berson, E. L., Dryja, T. P.
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<strong>Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or Leber congenital amaurosis.</strong>
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Proc. Nat. Acad. Sci. 95: 3088-3093, 1998.
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[PubMed: 9501220]
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[Full Text: https://doi.org/10.1073/pnas.95.6.3088]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Narfstrom, K., Wrigstad, A., Nilsson, S. E.
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<strong>The Briard dog: a new animal model of congenital stationary night blindness.</strong>
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Brit. J. Ophthal. 73: 750-756, 1989.
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[PubMed: 2804031]
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[Full Text: https://doi.org/10.1136/bjo.73.9.750]
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Schappert-Kimmijser, J., Henkes, H. E., Van den Bosch, J.
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<strong>Amaurosis congenita (Leber).</strong>
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AMA Arch. Ophthal. 61: 211-218, 1959.
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[PubMed: 13616783]
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[Full Text: https://doi.org/10.1001/archopht.1959.00940090213003]
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<p class="mim-text-font">
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Waardenburg, P. J., Schappert-Kimmijser, J.
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<strong>On various recessive biotypes of Leber's congenital amaurosis.</strong>
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Acta Ophthal. 41: 317-320, 1963.
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[PubMed: 14047474]
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[Full Text: https://doi.org/10.1111/j.1755-3768.1963.tb02444.x]
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Wrigstad, A., Narfstrom, K., Nilsson, S. E.
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<strong>Slowly progressive changes of the retina and retinal pigment epithelium in Briard dogs with hereditary retinal dystrophy: a morphological study.</strong>
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Doc. Ophthal. 87: 337-354, 1994.
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[PubMed: 7851218]
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[Full Text: https://doi.org/10.1007/BF01203343]
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Yzer, S., van den Born, L. I., Schuil, J., Kroes, H. Y., van Genderen, M. M., Boonstra, F. N., van den Helm, B., Brunner, H. G., Koenekoop, R. K., Cremers, F. P. M.
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<strong>A tyr368his RPE65 founder mutation is associated with variable expression and progression of early onset retinal dystrophy in 10 families of a genetically isolated population. (Letter)</strong>
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J. Med. Genet. 40: 709-713, 2003.
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[PubMed: 12960219]
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[Full Text: https://doi.org/10.1136/jmg.40.9.709]
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Marla J. F. O'Neill - updated : 4/6/2011<br>Ada Hamosh - updated : 3/19/2010<br>Marla J. F. O'Neill - updated : 3/1/2010<br>Marla J. F. O'Neill - updated : 8/20/2009<br>Victor A. McKusick - updated : 11/10/1998<br>Ada Hamosh - updated : 11/9/1998<br>Victor A. McKusick - updated : 9/26/1997
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Victor A. McKusick : 6/3/1986
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alopez : 04/27/2023<br>carol : 02/24/2022<br>carol : 06/12/2019<br>carol : 12/08/2016<br>alopez : 11/26/2012<br>wwang : 5/13/2011<br>wwang : 4/15/2011<br>terry : 4/6/2011<br>terry : 3/30/2011<br>carol : 3/28/2011<br>alopez : 3/22/2010<br>terry : 3/19/2010<br>carol : 3/1/2010<br>wwang : 9/14/2009<br>wwang : 9/9/2009<br>terry : 8/20/2009<br>carol : 4/3/2009<br>tkritzer : 8/6/2004<br>carol : 10/15/1999<br>terry : 6/11/1999<br>carol : 11/18/1998<br>terry : 11/10/1998<br>alopez : 11/9/1998<br>carol : 4/24/1998<br>mark : 9/26/1997<br>terry : 9/22/1997<br>terry : 9/22/1997<br>mimadm : 11/12/1995<br>warfield : 3/7/1994<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>ddp : 10/26/1989<br>marie : 3/25/1988
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