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<title>
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Entry
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- *600298 - LIM HOMEOBOX TRANSCRIPTION FACTOR 1, ALPHA; LMX1A
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- OMIM
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<div id="mimSearch" class="hidden-print">
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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<div class="input-group-btn">
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<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
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Advanced Search
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/entry"> OMIM </a>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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<a href="/search/advanced/geneMap"> Gene Map </a>
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</form>
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<p />
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<div class="row">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*600298</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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</li>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</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="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/600298">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
|
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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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 id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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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 panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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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="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000162761;t=ENST00000342310" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=4009" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=600298" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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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="mimDnaLinksFold" 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.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000162761;t=ENST00000342310" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001174069,NM_177398,XM_011509538,XM_011509540" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_177398" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=600298" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
|
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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="mimProteinLinksFold" 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://hprd.org/summary?hprd_id=02623&isoform_id=02623_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/LMX1A" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/19879681,19879682,27923801,28893581,42490861,111185587,111185589,114212259,119611149,119611150,193785405,291327513,767909279,767909283,2462509178,2462509180" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/Q8TE12" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" 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="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</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="mimGeneInfoLinksFold" 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="http://biogps.org/#goto=genereport&id=4009" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000162761;t=ENST00000342310" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=LMX1A" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=LMX1A" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+4009" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/LMX1A" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:4009" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/4009" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr1&hgg_gene=ENST00000342310.7&hgg_start=165201867&hgg_end=165356715&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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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="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="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 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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=600298[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>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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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="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=600298[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000162761" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=LMX1A" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=LMX1A" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=LMX1A" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=LMX1A&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA30416" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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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/gene/HGNC:6653" 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="https://flybase.org/reports/FBgn0052105.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1888519" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/LMX1A#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:1888519" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/4009/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=4009" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00002988;class=Gene" 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'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-041014-332" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
|
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</div>
|
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</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="mimCellularPathwaysLinksFold" 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://reactome.org/content/query?q=LMX1A&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></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>
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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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</span>
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</div>
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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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</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="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
|
600298
|
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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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LIM HOMEOBOX TRANSCRIPTION FACTOR 1, ALPHA; LMX1A
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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>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
LIM HOMEOBOX TRANSCRIPTION FACTOR 1; LMX1<br />
|
|
LMX1.1<br />
|
|
INSULIN-REGULATING TRANSCRIPTION FACTOR LMX1
|
|
</span>
|
|
</h4>
|
|
</div>
|
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</div>
|
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<div>
|
|
<br />
|
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</div>
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</div>
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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=LMX1A" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">LMX1A</a></em></strong>
|
|
</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/1/1373?start=-3&limit=10&highlight=1373">1q23.3</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:165201867-165356715&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">1:165,201,867-165,356,715</a> </span>
|
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</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
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|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/1/1373?start=-3&limit=10&highlight=1373">
|
|
1q23.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Deafness, autosomal dominant 7
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/601412"> 601412 </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">
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<p>The LMX1A gene encodes a transcription factor that plays an important role in various developmental processes, including neural progenitor specification and dopamine neurogenesis (summary by <a href="#10" class="mim-tip-reference" title="Wesdorp, M., de Koning Gans, P. A. M., Schraders, M., Oostrik, J., Huynen, M. A., Venselaar, H., Beynon, A. J., van Gaalen, J., Piai, V., Voermans, N., van Rossum, M. M., Hartel, B. P., and 14 others. <strong>Heterozygous missense variants of LMX1A lead to nonsyndromic hearing impairment and vestibular dysfunction.</strong> Hum. Genet. 137: 389-400, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29754270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29754270</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29754270[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/10.1007/s00439-018-1880-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29754270">Wesdorp et al., 2018</a> and <a href="#8" class="mim-tip-reference" title="Schrauwen, I., Chakchouk, I., Liaqat, K., Jan, A., Nasir, A., Hussain, S., Nickerson, D. A., Bamshad, M. J., Ullah, A., Ahmad, W., Leal, S. M. <strong>A variant in LMX1A causes autosomal recessive severe-to-profound hearing impairment.</strong> Hum. Genet. 137: 471-478, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29971487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29971487</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29971487[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/10.1007/s00439-018-1899-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29971487">Schrauwen et al., 2018</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=29971487+29754270" 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="#5" class="mim-tip-reference" title="German, M. S., Wang, J., Fernald, A. A., Espinosa, R., III, Le Beau, M. M., Bell, G. I. <strong>Localization of the genes encoding two transcription factors, LMX1 and CDX3, regulating insulin gene expression to human chromosomes 1 and 13.</strong> Genomics 24: 403-404, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7698771/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7698771</a>] [<a href="https://doi.org/10.1006/geno.1994.1639" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7698771">German et al. (1994)</a> isolated human genomic clones for the LMX1 and CDX3 (<a href="/entry/600297">600297</a>) genes from a human genomic library by cross-hybridization with cDNA clones encoding Syrian hamster proteins. The identities of the clones were confirmed by DNA sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7698771" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using in situ hybridization, <a href="#9" class="mim-tip-reference" title="Steffes, G., Lorente-Canovas, B., Pearson, S., Brooker, R. H., Spiden, S., Kiernan, A. E., Guenet, J. L., Steel, K. P. <strong>Mutanlallemand (mtl) and belly spot and deafness (bsd) are two new mutations of Lmx1a causing severe cochlear and vestibular defects.</strong> PLoS One 7: e51065, 2012. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23226461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23226461</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23226461[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/10.1371/journal.pone.0051065" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23226461">Steffes et al. (2012)</a> detected Lmx1a transcripts in otic vesicle and endolymphatic sac of developing inner ear of mouse embryos at embryonic day 10.5 (E10.5). At E12.5, Lmx1a transcripts were also found in the region of fusion plates that later form the semicircular canals. In tissues forming the labyrinth and the cochlear duct, Lmx1a transcripts were restricted to prospective nonsensory inner ear tissue. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23226461" 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>By fluorescence in situ hybridization, <a href="#5" class="mim-tip-reference" title="German, M. S., Wang, J., Fernald, A. A., Espinosa, R., III, Le Beau, M. M., Bell, G. I. <strong>Localization of the genes encoding two transcription factors, LMX1 and CDX3, regulating insulin gene expression to human chromosomes 1 and 13.</strong> Genomics 24: 403-404, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7698771/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7698771</a>] [<a href="https://doi.org/10.1006/geno.1994.1639" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7698771">German et al. (1994)</a> determined that the LMX1 gene is located on distal chromosome 1q22 or the junction of bands 1q22-q23. <a href="#4" class="mim-tip-reference" title="Church, D. M., Stotler, C. J., Rutter, J. L., Murrell, J. R., Trofatter, J. A., Buckler, A. J. <strong>Isolation of genes from complex sources of mammalian genomic DNA using exon amplification.</strong> Nature Genet. 6: 98-105, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8136842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8136842</a>] [<a href="https://doi.org/10.1038/ng0194-98" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8136842">Church et al. (1994)</a> identified a locus on chromosome 9 that appears to represent a closely related but distinct gene; see <a href="/entry/602575">602575</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7698771+8136842" 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>Insulin is produced exclusively by the beta cells in the islets of Langerhans in the pancreas. The level and beta-cell specificity of insulin gene expression are regulated by a set of nuclear genes that bind to specific sequences within the promoter of the insulin gene (INS; <a href="/entry/176730">176730</a>) and interact with RNA polymerase to activate or repress transcription. LMX1 is a homeodomain protein that binds an A/T-rich sequence in the insulin promoter and stimulates transcription of insulin (<a href="#5" class="mim-tip-reference" title="German, M. S., Wang, J., Fernald, A. A., Espinosa, R., III, Le Beau, M. M., Bell, G. I. <strong>Localization of the genes encoding two transcription factors, LMX1 and CDX3, regulating insulin gene expression to human chromosomes 1 and 13.</strong> Genomics 24: 403-404, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7698771/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7698771</a>] [<a href="https://doi.org/10.1006/geno.1994.1639" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7698771">German et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7698771" 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="#1" class="mim-tip-reference" title="Andersson, E., Tryggvason, U., Deng, Q., Friling, S., Alekseenko, Z., Robert, B., Perlmann, T., Ericson, J. <strong>Identification of intrinsic determinants of midbrain dopamine neurons.</strong> Cell 124: 393-405, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16439212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16439212</a>] [<a href="https://doi.org/10.1016/j.cell.2005.10.037" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16439212">Andersson et al. (2006)</a> showed that Lmx1a and Msx1 (<a href="/entry/142983">142983</a>) were determinants of midbrain dopamine neurons in mouse and chicken embryos. Lmx1a was necessary and sufficient to trigger dopamine cell differentiation, and early activity of Lmx1a induced expression of Msx1, which complemented Lmx1a by inducing expression of Ngn2 (NEUROG2; <a href="/entry/606624">606624</a>) and neuronal differentiation. Expression of Lmx1a in embryonic stem cells resulted in robust generation of dopamine neurons with midbrain identity. <a href="#1" class="mim-tip-reference" title="Andersson, E., Tryggvason, U., Deng, Q., Friling, S., Alekseenko, Z., Robert, B., Perlmann, T., Ericson, J. <strong>Identification of intrinsic determinants of midbrain dopamine neurons.</strong> Cell 124: 393-405, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16439212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16439212</a>] [<a href="https://doi.org/10.1016/j.cell.2005.10.037" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16439212">Andersson et al. (2006)</a> concluded that LMX1A and MSX1 are critical intrinsic dopamine neuron determinants. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16439212" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Caiazzo, M., Dell'Anno, M. T., Dvoretskova, E., Lazarevic, D., Taverna, S., Leo, D., Sotnikova, T. D., Menegon, A., Roncaglia, P., Colciago, G., Russo, G., Carninci, P., Pezzoli, G., Gainetdinov, R. R., Gustincich, S., Dityatev, A., Broccoli, V. <strong>Direct generation of functional dopaminergic neurons from mouse and human fibroblasts.</strong> Nature 476: 224-227, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21725324/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21725324</a>] [<a href="https://doi.org/10.1038/nature10284" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21725324">Caiazzo et al. (2011)</a> identified a minimal set of 3 transcription factors--Mash1 (<a href="/entry/100790">100790</a>), Nr4a2 (<a href="/entry/601828">601828</a>), and Lmx1a--that are able to generate directly functional dopaminergic neurons from mouse and human fibroblasts without reverting to a progenitor cell stage. Induced dopaminergic cells released dopamine and showed spontaneous electrical activity organized in regular spikes consistent with the pacemaker activity featured by brain dopaminergic neurons. The 3 factors were able to elicit dopaminergic neuronal conversion in prenatal and adult fibroblasts from healthy donors and Parkinson disease (<a href="/entry/168600">168600</a>) patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21725324" 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="Mann, Z. F., Galvez, H., Pedreno, D., Chen, Z., Chrysostomou, E., Zak, M., Kang, M., Canden, E., Daudet, N. <strong>Shaping of inner ear sensory organs through antagonistic interactions between Notch signalling and Lmx1a.</strong> elife 6: e33323, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29199954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29199954</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29199954[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/10.7554/eLife.33323" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29199954">Mann et al. (2017)</a> found that sensory organs and nonsensory cells in mouse and chicken inner ear were derived from a common pool of cells through progressive segregation. This process was regulated by mutually antagonistic Notch signaling and Lmx1a (or its functional ortholog in chicken, Lmx1b) signaling. Notch-mediated lateral induction promoted a prosensory fate, whereas Lmx1a signaling antagonized lateral induction and promoted a nonsensory fate. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29199954" 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>In affected members of 2 unrelated Dutch families with autosomal dominant deafness-7 (DFNA7; <a href="/entry/601412">601412</a>), <a href="#10" class="mim-tip-reference" title="Wesdorp, M., de Koning Gans, P. A. M., Schraders, M., Oostrik, J., Huynen, M. A., Venselaar, H., Beynon, A. J., van Gaalen, J., Piai, V., Voermans, N., van Rossum, M. M., Hartel, B. P., and 14 others. <strong>Heterozygous missense variants of LMX1A lead to nonsyndromic hearing impairment and vestibular dysfunction.</strong> Hum. Genet. 137: 389-400, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29754270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29754270</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29754270[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/10.1007/s00439-018-1880-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29754270">Wesdorp et al. (2018)</a> identified heterozygous missense mutations at highly conserved residues in the LMX1A gene (V241L, <a href="#0001">600298.0001</a> and C97S, <a href="#0002">600298.0002</a>). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Neither was found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, and the authors postulated haploinsufficiency as a pathogenetic mechanism. However, <a href="#10" class="mim-tip-reference" title="Wesdorp, M., de Koning Gans, P. A. M., Schraders, M., Oostrik, J., Huynen, M. A., Venselaar, H., Beynon, A. J., van Gaalen, J., Piai, V., Voermans, N., van Rossum, M. M., Hartel, B. P., and 14 others. <strong>Heterozygous missense variants of LMX1A lead to nonsyndromic hearing impairment and vestibular dysfunction.</strong> Hum. Genet. 137: 389-400, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29754270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29754270</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29754270[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/10.1007/s00439-018-1880-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29754270">Wesdorp et al. (2018)</a> noted that Lmx1a +/- mice have normal hearing (see ANIMAL MODEL and <a href="#9" class="mim-tip-reference" title="Steffes, G., Lorente-Canovas, B., Pearson, S., Brooker, R. H., Spiden, S., Kiernan, A. E., Guenet, J. L., Steel, K. P. <strong>Mutanlallemand (mtl) and belly spot and deafness (bsd) are two new mutations of Lmx1a causing severe cochlear and vestibular defects.</strong> PLoS One 7: e51065, 2012. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23226461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23226461</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23226461[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/10.1371/journal.pone.0051065" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23226461">Steffes et al., 2012</a>), which is not supportive of haploinsufficiency as the disease mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23226461+29754270" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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For discussion of a possible association between autosomal recessive deafness and variation in the LMX1A gene, see <a href="#0003">600298.0003</a>.</p>
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<p><a href="#2" class="mim-tip-reference" title="Bergstrom, D. E., Gagnon, L. H., Eicher, E. M. <strong>Genetic and physical mapping of the Dreher locus on mouse chromosome 1.</strong> Genomics 59: 291-299, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10444330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10444330</a>] [<a href="https://doi.org/10.1006/geno.1999.5873" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10444330">Bergstrom et al. (1999)</a> characterized the phenotype of the recessive 'dreher' (dr) mutant mouse, which was later demonstrated to be caused by mutation in the Lmx1a gene (<a href="#7" class="mim-tip-reference" title="Millonig, J. H., Millen, K. J., Hatten, M. E. <strong>The mouse Dreher gene Lmx1a controls formation of the roof plate in the vertebrate CNS.</strong> Nature 403: 764-769, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10693804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10693804</a>] [<a href="https://doi.org/10.1038/35001573" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10693804">Millonig et al., 2000</a>). Mice homozygous for the dr allele have ataxic gait, circling behavior, impaired righting reflex, hyperactivity, inner ear defects, deafness, and pigmentation abnormalities. Other features include cerebellar hypoplasia, cerebellar foliation and lamination abnormalities, neocortical disruptions of neuronal migration, underdeveloped Mullerian duct derivatives, and skeletal and skull defects. <a href="#2" class="mim-tip-reference" title="Bergstrom, D. E., Gagnon, L. H., Eicher, E. M. <strong>Genetic and physical mapping of the Dreher locus on mouse chromosome 1.</strong> Genomics 59: 291-299, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10444330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10444330</a>] [<a href="https://doi.org/10.1006/geno.1999.5873" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10444330">Bergstrom et al. (1999)</a> mapped the dr locus to mouse chromosome 1 in a region with syntenic homology to human chromosome 1q21-q23. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10444330+10693804" 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 the vertebrate central nervous system, a cascade of signals that originates in the ectoderm adjacent to the neural tube is propagated by the roof plate to dorsalize the neural tube. <a href="#7" class="mim-tip-reference" title="Millonig, J. H., Millen, K. J., Hatten, M. E. <strong>The mouse Dreher gene Lmx1a controls formation of the roof plate in the vertebrate CNS.</strong> Nature 403: 764-769, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10693804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10693804</a>] [<a href="https://doi.org/10.1038/35001573" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10693804">Millonig et al. (2000)</a> reported that the phenotype of a spontaneous neurologic mutant mouse, called 'dreher' (dr), results from a failure of the roof plate to develop. Dorsalization of the neural tube is consequently affected: dorsal interneurons in the spinal cord and granule neurons in the cerebellar cortex are lost, and the dorsal vertebral neural arches fail to form. <a href="#7" class="mim-tip-reference" title="Millonig, J. H., Millen, K. J., Hatten, M. E. <strong>The mouse Dreher gene Lmx1a controls formation of the roof plate in the vertebrate CNS.</strong> Nature 403: 764-769, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10693804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10693804</a>] [<a href="https://doi.org/10.1038/35001573" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10693804">Millonig et al. (2000)</a> used positional cloning to identify the gene mutant in dreher and found that the Lim homeodomain protein Lmx1a is affected in 3 different alleles of dreher. Lmx1a is expressed in the roof plate along the neuraxis during development of the central nervous system and is required for the development of the roof plate and, in turn, for specification of dorsal cell fates in the central nervous system and developing vertebrae. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10693804" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Steffes, G., Lorente-Canovas, B., Pearson, S., Brooker, R. H., Spiden, S., Kiernan, A. E., Guenet, J. L., Steel, K. P. <strong>Mutanlallemand (mtl) and belly spot and deafness (bsd) are two new mutations of Lmx1a causing severe cochlear and vestibular defects.</strong> PLoS One 7: e51065, 2012. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23226461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23226461</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23226461[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/10.1371/journal.pone.0051065" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23226461">Steffes et al. (2012)</a> reported that mice homozygous for either the spontaneous mutanlallemand (mtl) mutation or the spontaneous belly spot and deafness (bsd) mutation had similar phenotypes. Homozygotes exhibited circling, head bobbing, and hyperactivity, and were smaller with short tails and white belly patches compared with wildtype. Mutant mice lacked a Preyer reflex, had severe morphologic defects of inner ear, and were profoundly deaf. Heterozygous mice had normal hearing. Complementation tests suggested that both mtl and bsd were mutant alleles of the Lmx1a gene. The authors identified the mtl mutation as a point mutation in the 3-prime splice site of exon 4 of Lmx1a and the bsd mutation as a genomic deletion including exon 3 of Lmx1a. Quantitative RT-PCR analysis revealed that Lmx1a transcripts in both mtl and bsd mutants were significantly downregulated compared with wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23226461" 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="https://www.ncbi.nlm.nih.gov/clinvar?term=600298[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1571147567 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1571147567;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1571147567" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1571147567" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 3 affected members of a 3-generation Dutch family (W15-0551) with autosomal dominant deafness-7 (DFNA7; <a href="/entry/601412">601412</a>), <a href="#10" class="mim-tip-reference" title="Wesdorp, M., de Koning Gans, P. A. M., Schraders, M., Oostrik, J., Huynen, M. A., Venselaar, H., Beynon, A. J., van Gaalen, J., Piai, V., Voermans, N., van Rossum, M. M., Hartel, B. P., and 14 others. <strong>Heterozygous missense variants of LMX1A lead to nonsyndromic hearing impairment and vestibular dysfunction.</strong> Hum. Genet. 137: 389-400, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29754270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29754270</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29754270[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/10.1007/s00439-018-1880-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29754270">Wesdorp et al. (2018)</a> identified a heterozygous c.721G-C transversion (c.721G-C, NM_001174069.1) in the LMX1A gene, resulting in a val241-to-leu (V241L) substitution at a conserved residue in the homeodomain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing and linkage analysis, segregated with the disorder in the family. It was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, but the authors postulated haploinsufficiency as a pathogenetic mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29754270" 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>In 4 affected members of a 2-generation Dutch family (63136) with autosomal dominant deafness-7 (DFNA7; <a href="/entry/601412">601412</a>), <a href="#10" class="mim-tip-reference" title="Wesdorp, M., de Koning Gans, P. A. M., Schraders, M., Oostrik, J., Huynen, M. A., Venselaar, H., Beynon, A. J., van Gaalen, J., Piai, V., Voermans, N., van Rossum, M. M., Hartel, B. P., and 14 others. <strong>Heterozygous missense variants of LMX1A lead to nonsyndromic hearing impairment and vestibular dysfunction.</strong> Hum. Genet. 137: 389-400, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29754270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29754270</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29754270[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/10.1007/s00439-018-1880-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29754270">Wesdorp et al. (2018)</a> identified a heterozygous c.290G-C transversion (c.290G-C, NM_001174069.1) in the LMX1A gene, resulting in a cys97-to-ser (C97S) substitution at a highly conserved residue in the second LIM domain that binds zinc atoms and is essential for DNA binding. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing and linkage analysis, segregated with the disorder in the family. It was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, but the authors postulated haploinsufficiency as a pathogenetic mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29754270" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 VARIANT OF UNKNOWN SIGNIFICANCE</strong>
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LMX1A, ILE369THR (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs763320093;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs763320093</a>)
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs763320093 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs763320093;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs763320093?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs763320093" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs763320093" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000680188 OR RCV001003347 OR RCV001034598" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000680188, RCV001003347, RCV001034598" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000680188...</a>
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<p>This variant is classified as a variant of unknown significance because its contribution to an autosomal recessive sensorineural deafness has not been confirmed.</p><p>In 2 brothers, born of consanguineous Pakistani parents (family 4755), with early-onset profound sensorineural hearing loss, <a href="#8" class="mim-tip-reference" title="Schrauwen, I., Chakchouk, I., Liaqat, K., Jan, A., Nasir, A., Hussain, S., Nickerson, D. A., Bamshad, M. J., Ullah, A., Ahmad, W., Leal, S. M. <strong>A variant in LMX1A causes autosomal recessive severe-to-profound hearing impairment.</strong> Hum. Genet. 137: 471-478, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29971487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29971487</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29971487[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/10.1007/s00439-018-1899-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29971487">Schrauwen et al. (2018)</a> identified a homozygous c.1106T-C transition (c.1106T-C, NM_001174069) in the LMX1A gene, resulting in an ile369-to-thr (I369T) substitution in the conserved C-terminal region. The variant, which was found by a combination of homozygosity mapping and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was found at a low frequency (1.8 x 10(-5)) in only heterozygous state in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, but the authors postulated that I369T is a hypomorphic allele that may compromise LMX1A binding to DNA. The patients presented with congenital prelingual severe to profound hearing loss without vestibular disturbances. The mother was not available for detailed testing, but did not report any hearing loss. The father developed mild late-onset unilateral hearing impairment that was possibly associated with antibiotic intake. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29971487" 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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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="Andersson2006" class="mim-anchor"></a>
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[<a href="https://doi.org/10.1016/j.cell.2005.10.037" target="_blank">Full Text</a>]
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<a id="Bergstrom1999" class="mim-anchor"></a>
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Bergstrom, D. E., Gagnon, L. H., Eicher, E. M.
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<strong>Genetic and physical mapping of the Dreher locus on mouse chromosome 1.</strong>
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Genomics 59: 291-299, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10444330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10444330</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10444330" 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/10.1006/geno.1999.5873" target="_blank">Full Text</a>]
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Caiazzo, M., Dell'Anno, M. T., Dvoretskova, E., Lazarevic, D., Taverna, S., Leo, D., Sotnikova, T. D., Menegon, A., Roncaglia, P., Colciago, G., Russo, G., Carninci, P., Pezzoli, G., Gainetdinov, R. R., Gustincich, S., Dityatev, A., Broccoli, V.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21725324/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21725324</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21725324" 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/nature10284" target="_blank">Full Text</a>]
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<a id="Church1994" class="mim-anchor"></a>
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Church, D. M., Stotler, C. J., Rutter, J. L., Murrell, J. R., Trofatter, J. A., Buckler, A. J.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8136842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8136842</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8136842" 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/ng0194-98" target="_blank">Full Text</a>]
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German, M. S., Wang, J., Fernald, A. A., Espinosa, R., III, Le Beau, M. M., Bell, G. I.
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<strong>Localization of the genes encoding two transcription factors, LMX1 and CDX3, regulating insulin gene expression to human chromosomes 1 and 13.</strong>
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Genomics 24: 403-404, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7698771/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7698771</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7698771" 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/10.1006/geno.1994.1639" target="_blank">Full Text</a>]
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Mann, Z. F., Galvez, H., Pedreno, D., Chen, Z., Chrysostomou, E., Zak, M., Kang, M., Canden, E., Daudet, N.
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<strong>Shaping of inner ear sensory organs through antagonistic interactions between Notch signalling and Lmx1a.</strong>
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elife 6: e33323, 2017. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29199954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29199954</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29199954[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=29199954" 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/10.7554/eLife.33323" target="_blank">Full Text</a>]
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Millonig, J. H., Millen, K. J., Hatten, M. E.
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<strong>The mouse Dreher gene Lmx1a controls formation of the roof plate in the vertebrate CNS.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10693804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10693804</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10693804" 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/10.1038/35001573" target="_blank">Full Text</a>]
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<a id="Schrauwen2018" class="mim-anchor"></a>
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Schrauwen, I., Chakchouk, I., Liaqat, K., Jan, A., Nasir, A., Hussain, S., Nickerson, D. A., Bamshad, M. J., Ullah, A., Ahmad, W., Leal, S. M.
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<strong>A variant in LMX1A causes autosomal recessive severe-to-profound hearing impairment.</strong>
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Hum. Genet. 137: 471-478, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29971487/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29971487</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29971487[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=29971487" 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/s00439-018-1899-7" target="_blank">Full Text</a>]
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Steffes, G., Lorente-Canovas, B., Pearson, S., Brooker, R. H., Spiden, S., Kiernan, A. E., Guenet, J. L., Steel, K. P.
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<strong>Mutanlallemand (mtl) and belly spot and deafness (bsd) are two new mutations of Lmx1a causing severe cochlear and vestibular defects.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23226461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23226461</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23226461[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=23226461" 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/10.1371/journal.pone.0051065" target="_blank">Full Text</a>]
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Wesdorp, M., de Koning Gans, P. A. M., Schraders, M., Oostrik, J., Huynen, M. A., Venselaar, H., Beynon, A. J., van Gaalen, J., Piai, V., Voermans, N., van Rossum, M. M., Hartel, B. P., and 14 others.
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<strong>Heterozygous missense variants of LMX1A lead to nonsyndromic hearing impairment and vestibular dysfunction.</strong>
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Hum. Genet. 137: 389-400, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29754270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29754270</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29754270[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=29754270" 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/s00439-018-1880-5" target="_blank">Full Text</a>]
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 02/11/2020
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Bao Lige - updated : 09/09/2019<br>Ada Hamosh - updated : 8/24/2011<br>Patricia A. Hartz - updated : 7/5/2007<br>Ada Hamosh - updated : 3/6/2000<br>Victor A. McKusick - updated : 12/21/1999<br>Ada Hamosh - updated : 4/9/1998
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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 : 1/9/1995
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</span>
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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carol : 09/12/2024
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<span class="mim-text-font">
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carol : 02/13/2020<br>carol : 02/12/2020<br>ckniffin : 02/11/2020<br>mgross : 09/09/2019<br>mgross : 09/09/2019<br>alopez : 08/25/2011<br>terry : 8/24/2011<br>mgross : 8/6/2007<br>terry : 7/5/2007<br>terry : 3/18/2004<br>alopez : 3/6/2000<br>terry : 3/6/2000<br>terry : 3/6/2000<br>mcapotos : 1/4/2000<br>terry : 12/21/1999<br>carol : 8/11/1998<br>carol : 7/1/1998<br>terry : 4/27/1998<br>alopez : 4/10/1998<br>alopez : 4/9/1998<br>jamie : 2/4/1997<br>pfoster : 2/6/1995<br>carol : 1/9/1995
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<span class="mim-font">
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<strong>*</strong> 600298
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<h3>
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LIM HOMEOBOX TRANSCRIPTION FACTOR 1, ALPHA; LMX1A
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</h3>
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<br />
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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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<h4>
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<span class="mim-font">
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LIM HOMEOBOX TRANSCRIPTION FACTOR 1; LMX1<br />
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LMX1.1<br />
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INSULIN-REGULATING TRANSCRIPTION FACTOR LMX1
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</h4>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: LMX1A</em></strong>
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</span>
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</p>
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<strong>
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<em>
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Cytogenetic location: 1q23.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 1:165,201,867-165,356,715 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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<tbody>
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<td rowspan="1">
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<span class="mim-font">
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1q23.3
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<td>
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<span class="mim-font">
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Deafness, autosomal dominant 7
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</td>
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<span class="mim-font">
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601412
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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<span class="mim-font">
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<strong>TEXT</strong>
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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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</div>
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<span class="mim-text-font">
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<p>The LMX1A gene encodes a transcription factor that plays an important role in various developmental processes, including neural progenitor specification and dopamine neurogenesis (summary by Wesdorp et al., 2018 and Schrauwen et al., 2018). </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>Cloning and Expression</strong>
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</h4>
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<span class="mim-text-font">
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<p>German et al. (1994) isolated human genomic clones for the LMX1 and CDX3 (600297) genes from a human genomic library by cross-hybridization with cDNA clones encoding Syrian hamster proteins. The identities of the clones were confirmed by DNA sequencing. </p><p>Using in situ hybridization, Steffes et al. (2012) detected Lmx1a transcripts in otic vesicle and endolymphatic sac of developing inner ear of mouse embryos at embryonic day 10.5 (E10.5). At E12.5, Lmx1a transcripts were also found in the region of fusion plates that later form the semicircular canals. In tissues forming the labyrinth and the cochlear duct, Lmx1a transcripts were restricted to prospective nonsensory inner ear tissue. </p>
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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>By fluorescence in situ hybridization, German et al. (1994) determined that the LMX1 gene is located on distal chromosome 1q22 or the junction of bands 1q22-q23. Church et al. (1994) identified a locus on chromosome 9 that appears to represent a closely related but distinct gene; see 602575. </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>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Insulin is produced exclusively by the beta cells in the islets of Langerhans in the pancreas. The level and beta-cell specificity of insulin gene expression are regulated by a set of nuclear genes that bind to specific sequences within the promoter of the insulin gene (INS; 176730) and interact with RNA polymerase to activate or repress transcription. LMX1 is a homeodomain protein that binds an A/T-rich sequence in the insulin promoter and stimulates transcription of insulin (German et al., 1994). </p><p>Andersson et al. (2006) showed that Lmx1a and Msx1 (142983) were determinants of midbrain dopamine neurons in mouse and chicken embryos. Lmx1a was necessary and sufficient to trigger dopamine cell differentiation, and early activity of Lmx1a induced expression of Msx1, which complemented Lmx1a by inducing expression of Ngn2 (NEUROG2; 606624) and neuronal differentiation. Expression of Lmx1a in embryonic stem cells resulted in robust generation of dopamine neurons with midbrain identity. Andersson et al. (2006) concluded that LMX1A and MSX1 are critical intrinsic dopamine neuron determinants. </p><p>Caiazzo et al. (2011) identified a minimal set of 3 transcription factors--Mash1 (100790), Nr4a2 (601828), and Lmx1a--that are able to generate directly functional dopaminergic neurons from mouse and human fibroblasts without reverting to a progenitor cell stage. Induced dopaminergic cells released dopamine and showed spontaneous electrical activity organized in regular spikes consistent with the pacemaker activity featured by brain dopaminergic neurons. The 3 factors were able to elicit dopaminergic neuronal conversion in prenatal and adult fibroblasts from healthy donors and Parkinson disease (168600) patients. </p><p>Mann et al. (2017) found that sensory organs and nonsensory cells in mouse and chicken inner ear were derived from a common pool of cells through progressive segregation. This process was regulated by mutually antagonistic Notch signaling and Lmx1a (or its functional ortholog in chicken, Lmx1b) signaling. Notch-mediated lateral induction promoted a prosensory fate, whereas Lmx1a signaling antagonized lateral induction and promoted a nonsensory fate. </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>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>In affected members of 2 unrelated Dutch families with autosomal dominant deafness-7 (DFNA7; 601412), Wesdorp et al. (2018) identified heterozygous missense mutations at highly conserved residues in the LMX1A gene (V241L, 600298.0001 and C97S, 600298.0002). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Neither was found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, and the authors postulated haploinsufficiency as a pathogenetic mechanism. However, Wesdorp et al. (2018) noted that Lmx1a +/- mice have normal hearing (see ANIMAL MODEL and Steffes et al., 2012), which is not supportive of haploinsufficiency as the disease mechanism. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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For discussion of a possible association between autosomal recessive deafness and variation in the LMX1A gene, see 600298.0003.</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>Bergstrom et al. (1999) characterized the phenotype of the recessive 'dreher' (dr) mutant mouse, which was later demonstrated to be caused by mutation in the Lmx1a gene (Millonig et al., 2000). Mice homozygous for the dr allele have ataxic gait, circling behavior, impaired righting reflex, hyperactivity, inner ear defects, deafness, and pigmentation abnormalities. Other features include cerebellar hypoplasia, cerebellar foliation and lamination abnormalities, neocortical disruptions of neuronal migration, underdeveloped Mullerian duct derivatives, and skeletal and skull defects. Bergstrom et al. (1999) mapped the dr locus to mouse chromosome 1 in a region with syntenic homology to human chromosome 1q21-q23. </p><p>In the vertebrate central nervous system, a cascade of signals that originates in the ectoderm adjacent to the neural tube is propagated by the roof plate to dorsalize the neural tube. Millonig et al. (2000) reported that the phenotype of a spontaneous neurologic mutant mouse, called 'dreher' (dr), results from a failure of the roof plate to develop. Dorsalization of the neural tube is consequently affected: dorsal interneurons in the spinal cord and granule neurons in the cerebellar cortex are lost, and the dorsal vertebral neural arches fail to form. Millonig et al. (2000) used positional cloning to identify the gene mutant in dreher and found that the Lim homeodomain protein Lmx1a is affected in 3 different alleles of dreher. Lmx1a is expressed in the roof plate along the neuraxis during development of the central nervous system and is required for the development of the roof plate and, in turn, for specification of dorsal cell fates in the central nervous system and developing vertebrae. </p><p>Steffes et al. (2012) reported that mice homozygous for either the spontaneous mutanlallemand (mtl) mutation or the spontaneous belly spot and deafness (bsd) mutation had similar phenotypes. Homozygotes exhibited circling, head bobbing, and hyperactivity, and were smaller with short tails and white belly patches compared with wildtype. Mutant mice lacked a Preyer reflex, had severe morphologic defects of inner ear, and were profoundly deaf. Heterozygous mice had normal hearing. Complementation tests suggested that both mtl and bsd were mutant alleles of the Lmx1a gene. The authors identified the mtl mutation as a point mutation in the 3-prime splice site of exon 4 of Lmx1a and the bsd mutation as a genomic deletion including exon 3 of Lmx1a. Quantitative RT-PCR analysis revealed that Lmx1a transcripts in both mtl and bsd mutants were significantly downregulated compared with wildtype. </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>ALLELIC VARIANTS</strong>
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</span>
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<strong>3 Selected Examples):</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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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 DEAFNESS, AUTOSOMAL DOMINANT 7</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMX1A, VAL241LEU
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<br />
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SNP: rs1571147567,
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ClinVar: RCV001003345
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 3 affected members of a 3-generation Dutch family (W15-0551) with autosomal dominant deafness-7 (DFNA7; 601412), Wesdorp et al. (2018) identified a heterozygous c.721G-C transversion (c.721G-C, NM_001174069.1) in the LMX1A gene, resulting in a val241-to-leu (V241L) substitution at a conserved residue in the homeodomain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing and linkage analysis, segregated with the disorder in the family. It was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, but the authors postulated haploinsufficiency as a pathogenetic mechanism. </p>
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</span>
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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>.0002 DEAFNESS, AUTOSOMAL DOMINANT 7</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMX1A, CYS97SER
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<br />
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SNP: rs1571177726,
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ClinVar: RCV001003346
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<div>
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<span class="mim-text-font">
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<p>In 4 affected members of a 2-generation Dutch family (63136) with autosomal dominant deafness-7 (DFNA7; 601412), Wesdorp et al. (2018) identified a heterozygous c.290G-C transversion (c.290G-C, NM_001174069.1) in the LMX1A gene, resulting in a cys97-to-ser (C97S) substitution at a highly conserved residue in the second LIM domain that binds zinc atoms and is essential for DNA binding. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing and linkage analysis, segregated with the disorder in the family. It was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, but the authors postulated haploinsufficiency as a pathogenetic mechanism. </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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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 VARIANT OF UNKNOWN SIGNIFICANCE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LMX1A, ILE369THR ({dbSNP rs763320093})
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<br />
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SNP: rs763320093,
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gnomAD: rs763320093,
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ClinVar: RCV000680188, RCV001003347, RCV001034598
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>This variant is classified as a variant of unknown significance because its contribution to an autosomal recessive sensorineural deafness has not been confirmed.</p><p>In 2 brothers, born of consanguineous Pakistani parents (family 4755), with early-onset profound sensorineural hearing loss, Schrauwen et al. (2018) identified a homozygous c.1106T-C transition (c.1106T-C, NM_001174069) in the LMX1A gene, resulting in an ile369-to-thr (I369T) substitution in the conserved C-terminal region. The variant, which was found by a combination of homozygosity mapping and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was found at a low frequency (1.8 x 10(-5)) in only heterozygous state in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, but the authors postulated that I369T is a hypomorphic allele that may compromise LMX1A binding to DNA. The patients presented with congenital prelingual severe to profound hearing loss without vestibular disturbances. The mother was not available for detailed testing, but did not report any hearing loss. The father developed mild late-onset unilateral hearing impairment that was possibly associated with antibiotic intake. </p>
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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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Bergstrom, D. E., Gagnon, L. H., Eicher, E. M.
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<strong>Genetic and physical mapping of the Dreher locus on mouse chromosome 1.</strong>
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Caiazzo, M., Dell'Anno, M. T., Dvoretskova, E., Lazarevic, D., Taverna, S., Leo, D., Sotnikova, T. D., Menegon, A., Roncaglia, P., Colciago, G., Russo, G., Carninci, P., Pezzoli, G., Gainetdinov, R. R., Gustincich, S., Dityatev, A., Broccoli, V.
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<strong>Direct generation of functional dopaminergic neurons from mouse and human fibroblasts.</strong>
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Nature 476: 224-227, 2011.
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Church, D. M., Stotler, C. J., Rutter, J. L., Murrell, J. R., Trofatter, J. A., Buckler, A. J.
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<strong>Isolation of genes from complex sources of mammalian genomic DNA using exon amplification.</strong>
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Nature Genet. 6: 98-105, 1994.
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German, M. S., Wang, J., Fernald, A. A., Espinosa, R., III, Le Beau, M. M., Bell, G. I.
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<strong>Localization of the genes encoding two transcription factors, LMX1 and CDX3, regulating insulin gene expression to human chromosomes 1 and 13.</strong>
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Genomics 24: 403-404, 1994.
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<p class="mim-text-font">
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Mann, Z. F., Galvez, H., Pedreno, D., Chen, Z., Chrysostomou, E., Zak, M., Kang, M., Canden, E., Daudet, N.
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<strong>Shaping of inner ear sensory organs through antagonistic interactions between Notch signalling and Lmx1a.</strong>
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[Full Text: https://doi.org/10.7554/eLife.33323]
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<li>
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<p class="mim-text-font">
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Millonig, J. H., Millen, K. J., Hatten, M. E.
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<strong>The mouse Dreher gene Lmx1a controls formation of the roof plate in the vertebrate CNS.</strong>
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Nature 403: 764-769, 2000.
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[Full Text: https://doi.org/10.1038/35001573]
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<p class="mim-text-font">
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Schrauwen, I., Chakchouk, I., Liaqat, K., Jan, A., Nasir, A., Hussain, S., Nickerson, D. A., Bamshad, M. J., Ullah, A., Ahmad, W., Leal, S. M.
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<strong>A variant in LMX1A causes autosomal recessive severe-to-profound hearing impairment.</strong>
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Hum. Genet. 137: 471-478, 2018.
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[Full Text: https://doi.org/10.1007/s00439-018-1899-7]
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<p class="mim-text-font">
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Steffes, G., Lorente-Canovas, B., Pearson, S., Brooker, R. H., Spiden, S., Kiernan, A. E., Guenet, J. L., Steel, K. P.
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<strong>Mutanlallemand (mtl) and belly spot and deafness (bsd) are two new mutations of Lmx1a causing severe cochlear and vestibular defects.</strong>
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PLoS One 7: e51065, 2012. Note: Electronic Article.
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[PubMed: 23226461]
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[Full Text: https://doi.org/10.1371/journal.pone.0051065]
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<p class="mim-text-font">
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Wesdorp, M., de Koning Gans, P. A. M., Schraders, M., Oostrik, J., Huynen, M. A., Venselaar, H., Beynon, A. J., van Gaalen, J., Piai, V., Voermans, N., van Rossum, M. M., Hartel, B. P., and 14 others.
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<strong>Heterozygous missense variants of LMX1A lead to nonsyndromic hearing impairment and vestibular dysfunction.</strong>
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Hum. Genet. 137: 389-400, 2018.
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[PubMed: 29754270]
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[Full Text: https://doi.org/10.1007/s00439-018-1880-5]
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Contributors:
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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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Cassandra L. Kniffin - updated : 02/11/2020<br>Bao Lige - updated : 09/09/2019<br>Ada Hamosh - updated : 8/24/2011<br>Patricia A. Hartz - updated : 7/5/2007<br>Ada Hamosh - updated : 3/6/2000<br>Victor A. McKusick - updated : 12/21/1999<br>Ada Hamosh - updated : 4/9/1998
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<span class="mim-text-font">
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Victor A. McKusick : 1/9/1995
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carol : 09/12/2024<br>carol : 02/13/2020<br>carol : 02/12/2020<br>ckniffin : 02/11/2020<br>mgross : 09/09/2019<br>mgross : 09/09/2019<br>alopez : 08/25/2011<br>terry : 8/24/2011<br>mgross : 8/6/2007<br>terry : 7/5/2007<br>terry : 3/18/2004<br>alopez : 3/6/2000<br>terry : 3/6/2000<br>terry : 3/6/2000<br>mcapotos : 1/4/2000<br>terry : 12/21/1999<br>carol : 8/11/1998<br>carol : 7/1/1998<br>terry : 4/27/1998<br>alopez : 4/10/1998<br>alopez : 4/9/1998<br>jamie : 2/4/1997<br>pfoster : 2/6/1995<br>carol : 1/9/1995
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