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Entry
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- *603681 - OTOFERLIN; OTOF
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- OMIM
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<p>
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<span class="h4">*603681</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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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="#cloning">Cloning and Expression</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/603681">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<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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<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 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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<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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</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=ENSG00000115155;t=ENST00000272371" 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=9381" 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=603681" 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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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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=ENSG00000115155;t=ENST00000272371" 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_001287489,NM_004802,NM_194248,NM_194322,NM_194323" 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_194248" 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=603681" 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=04727&isoform_id=04727_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/OTOF" 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/4588470,10119916,10119918,10442756,34740331,35493853,35493860,35493868,62822535,116242695,119621087,119621088,119621089,119621090,119621091,119621092,184161291,184161293,194382852,566559996" 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/Q9HC10" 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=9381" 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=ENSG00000115155;t=ENST00000272371" 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=OTOF" 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=OTOF" 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+9381" 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/OTOF" 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:9381" 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/9381" 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=chr2&hgg_gene=ENST00000272371.7&hgg_start=26457203&hgg_end=26558756&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://search.clinicalgenome.org/kb/gene-dosage/HGNC:8515" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:8515" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=603681[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=603681[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://www.deciphergenomics.org/gene/OTOF/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000115155" 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=OTOF" 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=OTOF" 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=OTOF" 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="#mimLocusSpecificDBsFold" id="mimLocusSpecificDBsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A gene-specific database of variation."><span id="mimLocusSpecificDBsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Locus Specific DBs</div>
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<div id="mimLocusSpecificDBsFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="http://webh01.ua.ac.be/hhh/" title="Hereditary Hearing Loss Homepage" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Hereditary Hearing Loss Ho…</a></div><div style="margin-left: 0.5em;"><a href="https://research.cchmc.org/LOVD2/home.php?select_db=OTOF" title="CCHMC Molecular Genetics Laboratory Mutation Database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">CCHMC Molecular Genetics L…</a></div>
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</div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=OTOF&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/PA32841" 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:8515" 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/FBgn0266757.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:1891247" 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/OTOF#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:1891247" 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/9381/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://omia.org/OMIA002413/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=9381" 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=WBGene00001414;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-030131-7778" 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">
|
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<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">
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<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=OTOF&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>
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603681
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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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OTOFERLIN; OTOF
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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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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=OTOF" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">OTOF</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/2/108?start=-3&limit=10&highlight=108">2p23.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:26457203-26558756&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'})">2:26,457,203-26,558,756</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="2">
|
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<span class="mim-font">
|
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<a href="/geneMap/2/108?start=-3&limit=10&highlight=108">
|
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2p23.3
|
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</a>
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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Auditory neuropathy, autosomal recessive, 1
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</span>
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</td>
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<td>
|
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<span class="mim-font">
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<a href="/entry/601071"> 601071 </a>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
|
Deafness, autosomal recessive 9
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/601071"> 601071 </a>
|
|
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
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<p>Using a candidate gene approach in the critical region of chromosome 2p23.1 for a form of nonsyndromic deafness (DFNB9; <a href="/entry/601071">601071</a>), <a href="#19" class="mim-tip-reference" title="Yasunaga, S., Grati, M., Cohen-Salmon, M., El-Amraoui, A., Mustapha, M., Salem, N., El-Zir, E., Loiselet, J., Petit, C. <strong>A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness.</strong> Nature Genet. 21: 363-369, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10192385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10192385</a>] [<a href="https://doi.org/10.1038/7693" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10192385">Yasunaga et al. (1999)</a> identified a novel human gene, which they called OTOF. ESTs in this region were submitted to rounds of 5-prime RACE-PCR and the deduced amino acids were compared with clones isolated from 2 subtracted mouse cochlear cDNA libraries. The human OTOF gene encodes a 4,954-bp transcript with a 3,690-bp open reading frame and a 1,038-bp 3-prime untranslated region with a polyadenylation signal at position 4934. The deduced 1,230-amino acid protein has a calculated molecular mass of 140.5 kD. It has 3 C2 domains and a single carboxy-terminal transmembrane domain. The protein is homologous to the C. elegans spermatogenesis factor FER-1 and human dysferlin (<a href="/entry/603009">603009</a>), prompting the authors to name it 'otoferlin.' The homology suggests the otoferlin is involved in vesicle membrane fusion. Otof expression was identified by RT-PCR in mouse cochlea, vestibule, and brain. By in situ hybridization, Otof labeling was seen in the inner hair cells, and faintly in the outer hair cells and spiral ganglion cells, at embryonic day 19.5, P0, and P2. Neuroepithelia of the utricle, saccule, and semicircular canals expressed Otof during the same days. Type I cells, but not type II cells or supporting cells, expressed Otof. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10192385" 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>By Northern blot analysis, <a href="#18" class="mim-tip-reference" title="Yasunaga, S., Grati, M., Chardenoux, S., Smith, T. N., Friedman, T. B., Lalwani, A. K., Wilcox, E. R., Petit, C. <strong>OTOF encodes multiple long and short isoforms: genetic evidence that the long ones underlie recessive deafness DFNB9.</strong> Am. J. Hum. Genet. 67: 591-600, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10903124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10903124</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10903124[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/10.1086/303049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10903124">Yasunaga et al. (2000)</a> detected a 7-kb otoferlin mRNA in the human brain. They isolated a corresponding cDNA, which was predicted to encode a 1,977-long form of otoferlin with 6 C2 domains. Other alternatively spliced transcripts were detected, which predicted several long isoforms (with 6 C2 domains) in humans and mice and short isoforms (3 C2 domains) only in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10903124" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Choi, B. Y., Ahmed, Z. M., Riazuddin, S., Bhinder, M. A., Shahzad, M., Husnain, T., Riazuddin, S., Griffith, A. J., Friedman, T. B. <strong>Identities and frequencies of mutations of the otoferlin gene (OTOF) causing DFNB9 deafness in Pakistan.</strong> Clin. Genet. 75: 237-243, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19250381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19250381</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2008.01128.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19250381">Choi et al. (2009)</a> demonstrated the existence of an alternative splice isoform of OTOF expressed in the human cochlea, and observed that human cochlear transcripts exclusively used exon 48 to encode the C-terminal 60 amino acids of this isoform, which lacks exon 47. The authors concluded that this isoform must be required for human hearing because it encodes a unique alternative C terminus affected by some DFNB9 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19250381" 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="#19" class="mim-tip-reference" title="Yasunaga, S., Grati, M., Cohen-Salmon, M., El-Amraoui, A., Mustapha, M., Salem, N., El-Zir, E., Loiselet, J., Petit, C. <strong>A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness.</strong> Nature Genet. 21: 363-369, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10192385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10192385</a>] [<a href="https://doi.org/10.1038/7693" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10192385">Yasunaga et al. (1999)</a> found that the OTOF gene extends over 21 kb and contains at least 28 coding exons, a 5-prime UTR exon, and a 3-prime UTR exon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10192385" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Yasunaga, S., Grati, M., Chardenoux, S., Smith, T. N., Friedman, T. B., Lalwani, A. K., Wilcox, E. R., Petit, C. <strong>OTOF encodes multiple long and short isoforms: genetic evidence that the long ones underlie recessive deafness DFNB9.</strong> Am. J. Hum. Genet. 67: 591-600, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10903124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10903124</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10903124[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/10.1086/303049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10903124">Yasunaga et al. (2000)</a> found that the OTOF gene contains 48 coding exons and spans approximately 90 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10903124" 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 analysis of a contig containing 8 YACs, 12 BACs, and 4 PACs, <a href="#20" class="mim-tip-reference" title="Yasunaga, S., Petit, C. <strong>Physical map of the region surrounding the otoferlin locus on chromosome 2p22-p23.</strong> Genomics 66: 110-112, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10843812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10843812</a>] [<a href="https://doi.org/10.1006/geno.2000.6185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10843812">Yasunaga and Petit (2000)</a> refined the mapping of OTOF and its surrounding genes on 2p23-p22. The authors oriented the 5-prime region of OTOF as centromeric. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10843812" 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="#13" class="mim-tip-reference" title="Roux, I., Safieddine, S., Nouvian, R., Grati, M., Simmler, M.-C., Bahloul, A., Perfettini, I., Le Gall, M., Rostaing, P., Hamard, G., Triller, A., Avan, P., Moser, T., Petit, C. <strong>Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse.</strong> Cell 127: 277-289, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17055430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17055430</a>] [<a href="https://doi.org/10.1016/j.cell.2006.08.040" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17055430">Roux et al. (2006)</a> showed that otoferlin expression in mouse hair cells correlated with afferent synaptogenesis, and they found that otoferlin localized to ribbon-associated synaptic vesicles. Otoferlin bound Ca(2+) and displayed Ca(2+)-dependent interactions with the SNARE proteins syntaxin-1 (STX1A; <a href="/entry/186590">186590</a>) and SNAP25 (<a href="/entry/600322">600322</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17055430" 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>Otoferlin has been proposed to be the calcium sensor in hair cell exocytosis, compensating for the classic synaptic fusion proteins synaptotagmin-1 (SYT1; <a href="/entry/185605">185605</a>) and synaptotagmin-2 (SYT2; <a href="/entry/600104">600104</a>). <a href="#6" class="mim-tip-reference" title="Heidrych, P., Zimmermann, U., Kuhn, S., Franz, C., Engel, J., Duncker, S. V., Hirt, B., Pusch, C. M., Ruth, P., Pfister, M., Marcotti, W., Blin, N., Knipper, M. <strong>Otoferlin interacts with myosin VI: implications for maintenance of the basolateral synaptic structure of the inner hair cell.</strong> Hum. Molec. Genet. 18: 2779-2790, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19417007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19417007</a>] [<a href="https://doi.org/10.1093/hmg/ddp213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19417007">Heidrych et al. (2009)</a> demonstrated in a yeast 2-hybrid assay that myosin VI (MYO6; <a href="/entry/600970">600970</a>) is a novel otoferlin-binding partner. Coimmunoprecipitation assay and coexpression suggested an interaction of both proteins within the basolateral part of inner hair cells (IHCs). Comparison of Otof-mutant and Myo6-mutant mice indicated noncomplementary and complementary roles of myosin VI and otoferlin for synaptic maturation. IHCs from Otof-mutant mice exhibited a decoupling of Ctbp2 (<a href="/entry/602619">602619</a>) and CaV1.3 (CACNA1D; <a href="/entry/114206">114206</a>) and severe reduction of exocytosis. Myo6-mutant IHCs failed to transport BK channels to the membrane of the apical cell regions, and the exocytotic Ca(2+) efficiency did not mature, and Otof- and Myo6-mutant IHCs showed a reduced basolateral synaptic surface area and altered active zone topography. Membrane infoldings in Otof-mutant inner hair cells indicated disturbed transport of endocytotic membranes and linked the above morphologic changes to a complementary role of otoferlin and myosin VI in transport of intracellular compartments to the basolateral inner hair cell membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19417007" 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="#19" class="mim-tip-reference" title="Yasunaga, S., Grati, M., Cohen-Salmon, M., El-Amraoui, A., Mustapha, M., Salem, N., El-Zir, E., Loiselet, J., Petit, C. <strong>A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness.</strong> Nature Genet. 21: 363-369, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10192385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10192385</a>] [<a href="https://doi.org/10.1038/7693" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10192385">Yasunaga et al. (1999)</a> identified a nonsense mutation (tyr703 to ter; <a href="#0001">603681.0001</a>) in the OTOF gene in all affected members of 4 unrelated Lebanese families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10192385" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Yasunaga, S., Grati, M., Chardenoux, S., Smith, T. N., Friedman, T. B., Lalwani, A. K., Wilcox, E. R., Petit, C. <strong>OTOF encodes multiple long and short isoforms: genetic evidence that the long ones underlie recessive deafness DFNB9.</strong> Am. J. Hum. Genet. 67: 591-600, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10903124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10903124</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10903124[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/10.1086/303049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10903124">Yasunaga et al. (2000)</a> studied a consanguineous family originating from India in which 3 sibs suffered from severe to profound hearing loss. By segregation analysis with polymorphic markers of the DFNB9 chromosomal region, they concluded that an OTOF mutation was likely to underlie deafness in this family. By sequencing the 48 OTOF coding exons in members of this family, they identified a splice mutation in intron 8 (<a href="#0002">603681.0002</a>). These studies demonstrated that the long otoferlin isoforms are required for inner ear function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10903124" 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="Adato, A., Raskin, L., Petit, C., Bonne-Tamir, B. <strong>Deafness heterogeneity in a Druze isolate from the Middle East: novel OTOF and PDS mutations, low prevalence of GJB2 35delG mutation and indication for a new DFNB locus.</strong> Europ. J. Hum. Genet. 8: 437-442, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10878664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10878664</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200489" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10878664">Adato et al. (2000)</a> studied the molecular basis of hearing impairment in 4 Druze families from the same village in northern Galilee. The Druze are a small, isolated population practicing endogamous marriage. Thus it was expected that a single mutation would account for hearing impairment in all these families. The results, however, showed that at least 4 different genes were involved. One was a new mutation in the OTOF gene (<a href="#0003">603681.0003</a>), the second was a mutation in the SLC26A4 gene (thr193 to ile; <a href="/entry/605646#0019">605646.0019</a>), and the third was a 35delG mutation in the GJB2 gene (<a href="/entry/121011#0005">121011.0005</a>). In the fourth family, linkage was excluded from all known hearing impairment loci (recessive and dominant), as well as from markers covering chromosomes 11 through 22, pointing therefore to the existence of another nonsyndromic recessive hearing loss locus on chromosomes 1 through 10. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10878664" 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 1 Cuban family, 2 Spanish families, and 8 sporadic Spanish patients with nonsyndromic sensorineural hearing loss, <a href="#9" class="mim-tip-reference" title="Migliosi, V., Modamio-Hoybjor, S., Moreno-Pelayo, M. A., Rodriguez-Ballesteros, M., Villamar, M., Telleria, D., Menendez, I., Moreno, F., del Castillo, I. <strong>Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is frequently found in Spanish patients with prelingual non-syndromic hearing loss.</strong> J. Med. Genet. 39: 502-506, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12114484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12114484</a>] [<a href="https://doi.org/10.1136/jmg.39.7.502" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12114484">Migliosi et al. (2002)</a> identified a gln829-to-ter mutation in exon 22 of the OTOF gene (Q829X; <a href="#0004">603681.0004</a>). <a href="#9" class="mim-tip-reference" title="Migliosi, V., Modamio-Hoybjor, S., Moreno-Pelayo, M. A., Rodriguez-Ballesteros, M., Villamar, M., Telleria, D., Menendez, I., Moreno, F., del Castillo, I. <strong>Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is frequently found in Spanish patients with prelingual non-syndromic hearing loss.</strong> J. Med. Genet. 39: 502-506, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12114484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12114484</a>] [<a href="https://doi.org/10.1136/jmg.39.7.502" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12114484">Migliosi et al. (2002)</a> determined that the Q829X mutation was responsible for 4.4% of recessive familial or sporadic cases of deafness in the Spanish population, and presented evidence for a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12114484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Rodriguez-Ballesteros, M., del Castillo, F. J., Martin, Y., Moreno-Pelayo, M. A., Morera, C., Prieto, F., Marco, J., Morant, A., Gallo-Teran, J., Morales-Angulo, C., Navas, C., Trinidad, G., Tapia, M. C., Moreno, F., del Castillo, I. <strong>Auditory neuropathy in patients carrying mutations in the otoferlin gene (OTOF).</strong> Hum. Mutat. 22: 451-456, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14635104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14635104</a>] [<a href="https://doi.org/10.1002/humu.10274" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14635104">Rodriguez-Ballesteros et al. (2003)</a> extended the screening for the Q829X mutation to 289 additional unrelated families, finding 15 new cases, 9 of which were homozygous and 6 of which were heterozygous. All of them had a mode of inheritance compatible with an autosomal recessive pattern. Four previously undescribed mutations were identified. A total of 37 subjects with mutations in OTOF were studied clinically. They were phenotypically homogeneous, having profound hearing impairment with very early onset, as shown by pure-tone audiometry and auditory brainstem responses. No inner ear malformation was demonstrated by MRI and CT. Cochlear implants had been successfully provided in 10 subjects. They found that transient evoked otoacoustic emissions (TEOAEs) were present, either bilaterally or unilaterally, in 11 subjects. This raises questions about universal screening programs that use TEOAEs as the first detection test for hearing impairment in newborns, since this technique may overlook a nonnegligible proportion of cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14635104" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Almontashiri, N. A. M., Alswaid, A., Oza, A., Al-Mazrou, K. A., Elrehim, O., Tayoun, A. A., Rehm, H. L., Amr, S. S. <strong>Recurrent variants in OTOF are significant contributors to prelingual nonsyndromic hearing loss in Saudi patients.</strong> Genet. Med. 20: 536-544, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29048421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29048421</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29048421[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/10.1038/gim.2017.143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29048421">Almontashiri et al. (2018)</a> screened 33 Saudi hearing loss probands for mutations in hearing loss genes and identified mutations in 21 probands. One of 2 mutations in the OTOF gene, glu57-to-ter (<a href="#0014">603681.0014</a>) and arg1792-to-his (<a href="#0015">603681.0015</a>), was present in one-third of these individuals (7/21). Only 1 of the 33 probands had a homozygous GJB6 (<a href="/entry/604418">604418</a>) deletion, and no sequence variants were detected in GJB2 (<a href="/entry/121011">121011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29048421" 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="#8" class="mim-tip-reference" title="Matsunaga, T., Mutai, H., Kunishima, S., Namba, K., Morimoto, N., Shinjo, Y., Arimoto, Y., Kataoka, Y., Shintani, T., Morita, N., Sugiuchi, T., Masuda, S., Nakano, A., Taiji, H., Kaga, K. <strong>A prevalent founder mutation and genotype-phenotype correlations of OTOF in Japanese patients with auditory neuropathy.</strong> Clin. Genet. 82: 425-432, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22575033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22575033</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2012.01897.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22575033">Matsunaga et al. (2012)</a> identified an R1939Q (<a href="#0012">603681.0012</a>) mutation in the OTOF gene, in 13 (56.5%) of 23 Japanese patients with early-onset auditory neuropathy. Seven patients were homozygous for the mutation, 4 were compound heterozygous for R1939Q and a truncating or splice site mutation in OTOF, 1 was compound heterozygous for R1939Q and a nontruncating mutation in OTOF, and 1 was heterozygous for the R1939Q mutation. Haplotype analysis indicated a founder effect for the R1939Q mutation. Those who were homozygous for R1939Q or compound heterozygous for R1939Q and a truncating mutation had a consistent and severe phenotype, whereas the patient who was compound heterozygous for R1939Q and a nontruncating mutation had a less severe phenotype, with moderate hearing loss at age 29 years and sloping audiograms. The findings suggested that the R1939Q variant likely causes a severe impairment of protein function, and that, in general, truncating mutations cause a more severe phenotype than nontruncating mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22575033" 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>Among 64 patients with OTOF-related hearing loss from a large Japanese database, <a href="#7" class="mim-tip-reference" title="Iwasa, Y., Nishio, S., Yoshimura, H., Sugaya, A., Kataoka, Y., Maeda, Y., Kanda, Y., Nagai, K., Naito, Y., Yamazaki, H., Ikezono, T., Matsuda, H., and 34 others. <strong>Detailed clinical features and genotype-phenotype correlation in an OTOF-related hearing loss cohort in Japan.</strong> Hum. Genet. 141: 865-875, 2022. Note: Erratum: Hum. Genet. 141: 993-995, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34536124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34536124</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34536124[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/s00439-021-02351-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34536124">Iwasa et al. (2022)</a> found that all 27 patients homozygous for the R1939Q mutation, as well as 22 compound heterozygotes for R1939Q and a truncating mutation and 1 patient with 2 truncating mutations, showed profound hearing loss. Among patients with one or more nontruncating mutations other than R1939Q, almost half had mild to moderate hearing loss. The genotype-phenotype correlation in nontruncating mutations was unclear, with the same mutation sometimes causing different phenotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34536124" 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="#13" class="mim-tip-reference" title="Roux, I., Safieddine, S., Nouvian, R., Grati, M., Simmler, M.-C., Bahloul, A., Perfettini, I., Le Gall, M., Rostaing, P., Hamard, G., Triller, A., Avan, P., Moser, T., Petit, C. <strong>Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse.</strong> Cell 127: 277-289, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17055430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17055430</a>] [<a href="https://doi.org/10.1016/j.cell.2006.08.040" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17055430">Roux et al. (2006)</a> found that Otof -/- mice were profoundly deaf. Exocytosis in Otof -/- auditory inner hair cells was almost completely abolished, despite normal ribbon synapse morphogenesis and Ca(2+) current. <a href="#13" class="mim-tip-reference" title="Roux, I., Safieddine, S., Nouvian, R., Grati, M., Simmler, M.-C., Bahloul, A., Perfettini, I., Le Gall, M., Rostaing, P., Hamard, G., Triller, A., Avan, P., Moser, T., Petit, C. <strong>Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse.</strong> Cell 127: 277-289, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17055430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17055430</a>] [<a href="https://doi.org/10.1016/j.cell.2006.08.040" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17055430">Roux et al. (2006)</a> concluded that OTOF is essential for a late step of synaptic vesicle exocytosis and may act as the major Ca(2+) sensor triggering membrane fusion at the auditory inner hair cell ribbon synapse. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17055430" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80356600 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356600;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=rs80356600" 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=rs80356600" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In members of 4 unrelated Lebanese families (F, AB, K1, and K2) of disparate geographic origin affected with autosomal recessive deafness-9 (DFNB9; <a href="/entry/601071">601071</a>), <a href="#19" class="mim-tip-reference" title="Yasunaga, S., Grati, M., Cohen-Salmon, M., El-Amraoui, A., Mustapha, M., Salem, N., El-Zir, E., Loiselet, J., Petit, C. <strong>A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness.</strong> Nature Genet. 21: 363-369, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10192385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10192385</a>] [<a href="https://doi.org/10.1038/7693" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10192385">Yasunaga et al. (1999)</a> identified a homozygous T-to-A transversion at position 2416 in exon 18 of the OTOF gene, causing a tyr-to-stop substitution at codon 730. The mutation was not identified in 106 unrelated, unaffected individuals living in Lebanon. Family F was originally reported by <a href="#3" class="mim-tip-reference" title="Chaib, H., Place, C., Salem, N., Chardenoux, S., Vincent, C., Weissenbach, J., El-Zir, E., Loiselet, J., Petit, C. <strong>A gene responsible for a sensorineural nonsyndromic recessive deafness maps to chromosome 2p22-23.</strong> Hum. Molec. Genet. 5: 155-158, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8789454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8789454</a>] [<a href="https://doi.org/10.1093/hmg/5.1.155" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8789454">Chaib et al. (1996)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10192385+8789454" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80356584 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356584;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=rs80356584" 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=rs80356584" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006508 OR RCV003698743" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006508, RCV003698743" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006508...</a>
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<p>In a family from southwestern India, <a href="#18" class="mim-tip-reference" title="Yasunaga, S., Grati, M., Chardenoux, S., Smith, T. N., Friedman, T. B., Lalwani, A. K., Wilcox, E. R., Petit, C. <strong>OTOF encodes multiple long and short isoforms: genetic evidence that the long ones underlie recessive deafness DFNB9.</strong> Am. J. Hum. Genet. 67: 591-600, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10903124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10903124</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10903124[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/10.1086/303049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10903124">Yasunaga et al. (2000)</a> showed that deafness (DFNB9; <a href="/entry/601071">601071</a>) was due to homozygosity for an A-to-G transition at the intron 8/exon 9 junction (IVS8-2A-G) of the OTOF gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10903124" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2148047884 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2148047884;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=rs2148047884" 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=rs2148047884" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006509" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006509" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006509</a>
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<p><a href="#1" class="mim-tip-reference" title="Adato, A., Raskin, L., Petit, C., Bonne-Tamir, B. <strong>Deafness heterogeneity in a Druze isolate from the Middle East: novel OTOF and PDS mutations, low prevalence of GJB2 35delG mutation and indication for a new DFNB locus.</strong> Europ. J. Hum. Genet. 8: 437-442, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10878664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10878664</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200489" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10878664">Adato et al. (2000)</a> found that nonsyndromic deafness (DFNB9; <a href="/entry/601071">601071</a>) in a Druze family was due to homozygosity for a G-to-A transition at position +1, the first intronic nucleotide in the splice donor site of exon 5. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10878664" 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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<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> rs80356593 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356593;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/rs80356593?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=rs80356593" 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=rs80356593" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006511 OR RCV000211838 OR RCV000325939 OR RCV002227998 OR RCV004751204" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006511, RCV000211838, RCV000325939, RCV002227998, RCV004751204" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006511...</a>
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<p>Among 28 unrelated Spanish families with nonsyndromic sensorineural hearing loss (<a href="/entry/601071">601071</a>), <a href="#9" class="mim-tip-reference" title="Migliosi, V., Modamio-Hoybjor, S., Moreno-Pelayo, M. A., Rodriguez-Ballesteros, M., Villamar, M., Telleria, D., Menendez, I., Moreno, F., del Castillo, I. <strong>Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is frequently found in Spanish patients with prelingual non-syndromic hearing loss.</strong> J. Med. Genet. 39: 502-506, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12114484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12114484</a>] [<a href="https://doi.org/10.1136/jmg.39.7.502" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12114484">Migliosi et al. (2002)</a> identified 1 family with a mutation in the OTOF gene: a 2485C-T transition in exon 22, resulting in a premature stop codon, gln829 to ter (Q829X). Both parents were carriers of the mutation and their 2 affected children were homozygous. The mutation was not present in 200 unrelated Spanish controls with normal hearing. Genetic analysis of another 269 unrelated patients with hearing loss revealed 11 more cases (8 sporadic and 3 familial) of the Q829X mutation. One of these families was compound heterozygous for Q829X and P1825A (<a href="#0005">603681.0005</a>). <a href="#9" class="mim-tip-reference" title="Migliosi, V., Modamio-Hoybjor, S., Moreno-Pelayo, M. A., Rodriguez-Ballesteros, M., Villamar, M., Telleria, D., Menendez, I., Moreno, F., del Castillo, I. <strong>Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is frequently found in Spanish patients with prelingual non-syndromic hearing loss.</strong> J. Med. Genet. 39: 502-506, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12114484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12114484</a>] [<a href="https://doi.org/10.1136/jmg.39.7.502" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12114484">Migliosi et al. (2002)</a> determined that the Q829X mutation was responsible for 4.4% of recessive familial or sporadic cases of deafness in the Spanish population, and presented evidence for a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12114484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Varga, R., Avenarius, M. R., Kelley, P. M., Keats, B. J., Berlin, C. I., Hood, L. J., Morlet, T. G., Brashears, S. M., Starr, A., Cohn, E. S., Smith, R. J. H., Kimberling, W. J. <strong>OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele.</strong> J. Med. Genet. 43: 576-581, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16371502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16371502</a>] [<a href="https://doi.org/10.1136/jmg.2005.038612" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16371502">Varga et al. (2006)</a> found the Q829X mutation in 2 families. They referred to Q829X as the Hispanic mutation, it having been found in a group of Spanish families and 1 Cuban family as noted. They described it in a family from England with no known Hispanic ancestry. In a family of Mexican ancestry, the Q829X mutation was present in heterozygous state. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16371502" 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>.0005 DEAFNESS, AUTOSOMAL RECESSIVE 9</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28937591 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937591;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=rs28937591" 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=rs28937591" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006512" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006512" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006512</a>
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<p>In a Spanish family with sensorineural hearing loss (<a href="/entry/601071">601071</a>), <a href="#9" class="mim-tip-reference" title="Migliosi, V., Modamio-Hoybjor, S., Moreno-Pelayo, M. A., Rodriguez-Ballesteros, M., Villamar, M., Telleria, D., Menendez, I., Moreno, F., del Castillo, I. <strong>Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is frequently found in Spanish patients with prelingual non-syndromic hearing loss.</strong> J. Med. Genet. 39: 502-506, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12114484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12114484</a>] [<a href="https://doi.org/10.1136/jmg.39.7.502" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12114484">Migliosi et al. (2002)</a> identified compound heterozygosity for mutations in the OTOF gene: a 5473C-G transversion in exon 44, resulting in a pro1825-to-ala (P1825A) substitution, and Q829X (<a href="#0004">603681.0004</a>). The authors noted that P1825A was the first missense mutation identified in the OTOF gene, and that it alters a conserved residue in the sixth C2 domain of the long isoforms, a domain expected to bind calcium. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12114484" 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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<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> rs80356587 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356587;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/rs80356587?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=rs80356587" 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=rs80356587" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000021037 OR RCV002293239 OR RCV004589519" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000021037, RCV002293239, RCV004589519" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000021037...</a>
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<p>In a family with nonsyndromic recessive auditory neuropathy (see <a href="/entry/601071">601071</a>) characterized by hearing loss with normal function of the outer hair cells, <a href="#17" class="mim-tip-reference" title="Varga, R., Kelley, P. M., Keats, B. J., Starr, A., Leal, S. M., Cohn, E., Kimberling, W. J. <strong>Non-syndromic recessive auditory neuropathy is the result of mutations in the otoferlin (OTOF) gene (Letter)</strong> J. Med. Genet. 40: 45-50, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12525542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12525542</a>] [<a href="https://doi.org/10.1136/jmg.40.1.45" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12525542">Varga et al. (2003)</a> identified compound heterozygosity for mutations in the OTOF gene: a 1-bp deletion (1778G) in exon 16, leading to a stop codon, and a 6141G-A change, resulting in an arg-to-gln substitution in exon 48 (<a href="#0007">603681.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12525542" 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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<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> rs80356605 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356605;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/rs80356605?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=rs80356605" 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=rs80356605" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006510 OR RCV000021073 OR RCV003480023" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006510, RCV000021073, RCV003480023" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006510...</a>
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<p>For discussion of the 6141G-A change in the OTOF gene that was found in compound heterozygous state in patients with nonsyndromic recessive auditory neuropathy (see <a href="/entry/601071">601071</a>) by <a href="#17" class="mim-tip-reference" title="Varga, R., Kelley, P. M., Keats, B. J., Starr, A., Leal, S. M., Cohn, E., Kimberling, W. J. <strong>Non-syndromic recessive auditory neuropathy is the result of mutations in the otoferlin (OTOF) gene (Letter)</strong> J. Med. Genet. 40: 45-50, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12525542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12525542</a>] [<a href="https://doi.org/10.1136/jmg.40.1.45" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12525542">Varga et al. (2003)</a>, see <a href="#0006">603681.0006</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12525542" 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>.0008 AUDITORY NEUROPATHY, AUTOSOMAL RECESSIVE, 1</strong>
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OTOF, IVS39, +1, G-C
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80356602 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356602;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=rs80356602" 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=rs80356602" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006514 OR RCV000021068" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006514, RCV000021068" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006514...</a>
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<p>In a family with nonsyndromic recessive auditory neuropathy (see <a href="/entry/601071">601071</a>) characterized by hearing loss with normal function of the outer hair cells, <a href="#17" class="mim-tip-reference" title="Varga, R., Kelley, P. M., Keats, B. J., Starr, A., Leal, S. M., Cohn, E., Kimberling, W. J. <strong>Non-syndromic recessive auditory neuropathy is the result of mutations in the otoferlin (OTOF) gene (Letter)</strong> J. Med. Genet. 40: 45-50, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12525542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12525542</a>] [<a href="https://doi.org/10.1136/jmg.40.1.45" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12525542">Varga et al. (2003)</a> identified a heterozygous G-C transversion in the donor splice site of intron 39, which is predicted to result in a truncated protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12525542" 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>.0009 AUDITORY NEUROPATHY, AUTOSOMAL RECESSIVE, 1</strong>
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OTOF, PRO50ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908598 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908598;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=rs121908598" 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=rs121908598" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006515" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006515" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006515</a>
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<p>In a family with nonsyndromic recessive auditory neuropathy (see <a href="/entry/601071">601071</a>) characterized by hearing loss with normal function of the outer hair cells, <a href="#17" class="mim-tip-reference" title="Varga, R., Kelley, P. M., Keats, B. J., Starr, A., Leal, S. M., Cohn, E., Kimberling, W. J. <strong>Non-syndromic recessive auditory neuropathy is the result of mutations in the otoferlin (OTOF) gene (Letter)</strong> J. Med. Genet. 40: 45-50, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12525542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12525542</a>] [<a href="https://doi.org/10.1136/jmg.40.1.45" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12525542">Varga et al. (2003)</a> identified a heterozygous 6285C-G change in the OTOF gene, resulting in a pro50-to-arg (P50R) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12525542" 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>.0010 AUDITORY NEUROPATHY, AUTOSOMAL RECESSIVE, 1</strong>
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OTOF, LEU1011PRO
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80356596 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356596;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=rs80356596" 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=rs80356596" 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=RCV000006516 OR RCV000021054" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006516, RCV000021054" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006516...</a>
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<p>In 3 Turkish sibs with nonsyndromic recessive auditory neuropathy (see <a href="/entry/601071">601071</a>), <a href="#15" class="mim-tip-reference" title="Tekin, M., Akcayoz, D., Incesulu, A. <strong>A novel missense mutation in a C2 domain of OTOF results in autosomal recessive auditory neuropathy.</strong> Am. J. Med. Genet. 138A: 6-10, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16097006/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16097006</a>] [<a href="https://doi.org/10.1002/ajmg.a.30907" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16097006">Tekin et al. (2005)</a> identified a homozygous 3032T-C transition in exon 26 of the OTOF gene, resulting in a leu1011-to-pro (L1011P) substitution in the fourth C2 domain (C2D) of the protein. The consanguineous parents were heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16097006" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0011" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0011 AUDITORY NEUROPATHY, AUTOSOMAL RECESSIVE, 1</strong>
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AUDITORY NEUROPATHY, AUTOSOMAL RECESSIVE, 1, TEMPERATURE-SENSITIVE, INCLUDED
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OTOF, ILE515THR
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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> rs80356586 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356586;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/rs80356586?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=rs80356586" 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=rs80356586" 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=RCV000006517 OR RCV000021035 OR RCV000604852 OR RCV003555942" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006517, RCV000021035, RCV000604852, RCV003555942" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006517...</a>
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<p><a href="#10" class="mim-tip-reference" title="Mirghomizadeh, F., Pfister, M., Apaydin, F., Petit, C., Kupka, S., Pusch, C. M., Zenner, H. P., Blin, N. <strong>Substitutions in the conserved C2C domain of otoferlin cause DFNB9, a form of nonsyndromic autosomal recessive deafness.</strong> Neurobiol. Dis. 10: 157-164, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12127154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12127154</a>] [<a href="https://doi.org/10.1006/nbdi.2002.0488" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12127154">Mirghomizadeh et al. (2002)</a> described a consanguineous family from eastern Turkey in which members had profound prelingual hearing loss (see <a href="/entry/601071">601071</a>) and a 1544T-C transition in the OTOF gene causing an ile515-to-thr (I515T) substitution. Affected members of the family were homozygous for the I515T mutation and a second missense mutation, inherited in cis. Both mutations were in the C2C domain (third C2 domain), which is predicted to bind calcium. The alignment of otoferlin and otoferlin-related proteins revealed remarkable conservation of amino acids within the human and mouse C2C domains. <a href="#10" class="mim-tip-reference" title="Mirghomizadeh, F., Pfister, M., Apaydin, F., Petit, C., Kupka, S., Pusch, C. M., Zenner, H. P., Blin, N. <strong>Substitutions in the conserved C2C domain of otoferlin cause DFNB9, a form of nonsyndromic autosomal recessive deafness.</strong> Neurobiol. Dis. 10: 157-164, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12127154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12127154</a>] [<a href="https://doi.org/10.1006/nbdi.2002.0488" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12127154">Mirghomizadeh et al. (2002)</a> predicted that either of the 2 mutations would severely disrupt the structure of the C2C domain, with the I515T mutation resulting in the creation of a new myristylation site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12127154" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Varga, R., Avenarius, M. R., Kelley, P. M., Keats, B. J., Berlin, C. I., Hood, L. J., Morlet, T. G., Brashears, S. M., Starr, A., Cohn, E. S., Smith, R. J. H., Kimberling, W. J. <strong>OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele.</strong> J. Med. Genet. 43: 576-581, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16371502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16371502</a>] [<a href="https://doi.org/10.1136/jmg.2005.038612" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16371502">Varga et al. (2006)</a> reported the I515T mutation in heterozygous state in an individual who was observed to be temperature-sensitive for the auditory neuropathy phenotype (see <a href="/entry/601071">601071</a>). In the family reported by <a href="#14" class="mim-tip-reference" title="Starr, A., Sininger, Y., Winter, M., Derebery, M. J., Oba, S., Michalewski, H. J. <strong>Transient deafness due to temperature-sensitive auditory neuropathy.</strong> Ear Hear. 19: 169-179, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9657592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9657592</a>] [<a href="https://doi.org/10.1097/00003446-199806000-00001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9657592">Starr et al. (1998)</a>, <a href="#16" class="mim-tip-reference" title="Varga, R., Avenarius, M. R., Kelley, P. M., Keats, B. J., Berlin, C. I., Hood, L. J., Morlet, T. G., Brashears, S. M., Starr, A., Cohn, E. S., Smith, R. J. H., Kimberling, W. J. <strong>OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele.</strong> J. Med. Genet. 43: 576-581, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16371502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16371502</a>] [<a href="https://doi.org/10.1136/jmg.2005.038612" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16371502">Varga et al. (2006)</a> found that the proband had abnormal auditory brainstem response (ABR), present otoacoustic emissions (OAE), and relatively normal hearing until she became febrile, when OAE remained normal but hearing degraded, and ABR worsened from abnormal with unidentified waves I-III and delayed latency of the wave IV-V complex to being totally absent. The amount of decline in hearing in the proband was dependent on the degree of fever. A mild to moderate hearing loss was present when she had the temperature of 37.8 degrees centigrade and profound hearing loss was present at 38.1 degrees centigrade. The proband's brother, who also carried the mutation, experienced similar hearing loss when febrile. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16371502+9657592" 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>.0012 AUDITORY NEUROPATHY, AUTOSOMAL RECESSIVE, 1</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006510 OR RCV000021073 OR RCV003480023" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006510, RCV000021073, RCV003480023" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006510...</a>
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<p>In 13 (56.5%) of 23 Japanese patients with early-onset auditory neuropathy (see <a href="/entry/601071">601071</a>), <a href="#8" class="mim-tip-reference" title="Matsunaga, T., Mutai, H., Kunishima, S., Namba, K., Morimoto, N., Shinjo, Y., Arimoto, Y., Kataoka, Y., Shintani, T., Morita, N., Sugiuchi, T., Masuda, S., Nakano, A., Taiji, H., Kaga, K. <strong>A prevalent founder mutation and genotype-phenotype correlations of OTOF in Japanese patients with auditory neuropathy.</strong> Clin. Genet. 82: 425-432, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22575033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22575033</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2012.01897.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22575033">Matsunaga et al. (2012)</a> identified a 5816G-A transition in exon 50 of the OTOF gene, resulting in an arg1939-to-gln (R1939Q) substitution. Seven patients were homozygous for the mutation, 4 were compound heterozygous for R1939Q and a truncating or splice site mutation in OTOF, 1 was compound heterozygous for R1939Q and a nontruncating mutation in OTOF, and 1 was heterozygous for the R1939Q mutation. Haplotype analysis indicated a founder effect for the R1939Q mutation. The R1939Q mutation was found in 1 of 189 control individuals. Those who were homozygous for R1939Q or compound heterozygous for R1939Q and a truncating mutation had a consistent and severe phenotype, whereas the patient who was compound heterozygous for R1939Q and a nontruncating mutation had a less severe phenotype, with moderate hearing loss at age 29 years and sloping audiograms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22575033" 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>Among the 64 patients with DFNB9 identified in a large Japanese database, <a href="#7" class="mim-tip-reference" title="Iwasa, Y., Nishio, S., Yoshimura, H., Sugaya, A., Kataoka, Y., Maeda, Y., Kanda, Y., Nagai, K., Naito, Y., Yamazaki, H., Ikezono, T., Matsuda, H., and 34 others. <strong>Detailed clinical features and genotype-phenotype correlation in an OTOF-related hearing loss cohort in Japan.</strong> Hum. Genet. 141: 865-875, 2022. Note: Erratum: Hum. Genet. 141: 993-995, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34536124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34536124</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34536124[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/s00439-021-02351-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34536124">Iwasa et al. (2022)</a> found that 27 (42%) were homozygous for the R1939Q variant, and 29 (45%) were compound heterozygous for the R1939Q variant and another mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34536124" 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 a 26-year-old Japanese man, born of consanguineous parents, with temperature-sensitive auditory neuropathy (see <a href="/entry/601071">601071</a>), <a href="#8" class="mim-tip-reference" title="Matsunaga, T., Mutai, H., Kunishima, S., Namba, K., Morimoto, N., Shinjo, Y., Arimoto, Y., Kataoka, Y., Shintani, T., Morita, N., Sugiuchi, T., Masuda, S., Nakano, A., Taiji, H., Kaga, K. <strong>A prevalent founder mutation and genotype-phenotype correlations of OTOF in Japanese patients with auditory neuropathy.</strong> Clin. Genet. 82: 425-432, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22575033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22575033</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2012.01897.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22575033">Matsunaga et al. (2012)</a> identified a homozygous 1621G-A transition in exon 15 of the OTOF gene, resulting in a gly541-to-ser (G541S) substitution that was specific to the long isoform. The mutation was not found in 376 control individuals. The patient complained of difficulty in understanding conversation and reported that his hearing deteriorated when he became febrile or was exposed to loud noise. Pure-tone audiometry when he was afebrile revealed mild hearing loss with a flat configuration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22575033" 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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<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> rs397515591 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397515591;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/rs397515591?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=rs397515591" 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=rs397515591" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a 2-year-old child from a multiplex Libyan family with profound prelingual sensorineural hearing loss (DFNB9; <a href="/entry/601071">601071</a>), <a href="#12" class="mim-tip-reference" title="Rodriguez-Ballesteros, M., Reynoso, R., Olarte, M., Villamar, M., Morera, C., Santarelli, R., Arslan, E., Meda, C., Curet, C., Volter, C., Sainz-Quevedo, M., Castorina, P., and 16 others. <strong>A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and auditory neuropathy.</strong> Hum. Mutat. 29: 823-831, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18381613/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18381613</a>] [<a href="https://doi.org/10.1002/humu.20708" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18381613">Rodriguez-Ballesteros et al. (2008)</a> detected homozygosity for a c.2239G-T transversion in exon 20 of the OTOF gene that resulted in a glu747-to-ter (E747X) amino acid substitution. The authors noted that the mutation affected both the long and the short isoforms of OTOF. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18381613" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a Saudi Arabian brother and sister with severe to profound hearing impairment, <a href="#5" class="mim-tip-reference" title="Dallol, A., Daghistani, K., Elaimi, A., Al-Wazani, W. A., Bamanie, A., Safiah, M., Sagaty, S., Taha, L., Zahed, R., Bajouh, O., Chaudhary, A. G., Gari, M. A., Turki, R., Al-Qahtani, M. H., Abuzenadah, A. M. <strong>Utilization of amplicon-based targeted sequencing panel for the massively parallel sequencing of sporadic hearing impairment patients from Saudi Arabia.</strong> BMC Med. Genet. 17: 67, 2016. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27766948/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27766948</a>] [<a href="https://doi.org/10.1186/s12881-016-0329-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27766948">Dallol et al. (2016)</a> identified homozygosity for a c.2239G-T transversion (c.2239G-T, NM_194248) in the OTOF gene that resulted in an E747X amino acid substitution. The mutation was identified by targeted sequencing of 87 genes known to be involved in hearing impairment, and confirmed by Sanger sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27766948" 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 3 Saudi families (F-7, F-25, and F-27) with autosomal recessive prelingual sensorineural hearing loss, <a href="#2" class="mim-tip-reference" title="Almontashiri, N. A. M., Alswaid, A., Oza, A., Al-Mazrou, K. A., Elrehim, O., Tayoun, A. A., Rehm, H. L., Amr, S. S. <strong>Recurrent variants in OTOF are significant contributors to prelingual nonsyndromic hearing loss in Saudi patients.</strong> Genet. Med. 20: 536-544, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29048421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29048421</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29048421[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/10.1038/gim.2017.143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29048421">Almontashiri et al. (2018)</a> identified homozygosity for the E747X mutation in the OTOF gene, which they designated c.169G-T (GLU57TER, E57X). The mutation was identified by targeted sequencing and confirmed by Sanger sequencing. <a href="#2" class="mim-tip-reference" title="Almontashiri, N. A. M., Alswaid, A., Oza, A., Al-Mazrou, K. A., Elrehim, O., Tayoun, A. A., Rehm, H. L., Amr, S. S. <strong>Recurrent variants in OTOF are significant contributors to prelingual nonsyndromic hearing loss in Saudi patients.</strong> Genet. Med. 20: 536-544, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29048421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29048421</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29048421[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/10.1038/gim.2017.143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29048421">Almontashiri et al. (2018)</a> observed this variant in 1 of 251,632 alleles from non-Middle Eastern populations in the gnomAD database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29048421" 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>.0015 DEAFNESS, AUTOSOMAL RECESSIVE 9</strong>
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OTOF, ARG1792HIS (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033349;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs111033349</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> rs111033349 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033349;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/rs111033349?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=rs111033349" 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=rs111033349" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000041571 OR RCV000171287 OR RCV000656336" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000041571, RCV000171287, RCV000656336" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000041571...</a>
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<p>In affected members from 4 (F-18, F-22, F-31, and F-32) of 33 Saudi families with autosomal recessive prelingual sensorineural hearing loss (DFNB9; <a href="/entry/601071">601071</a>), <a href="#2" class="mim-tip-reference" title="Almontashiri, N. A. M., Alswaid, A., Oza, A., Al-Mazrou, K. A., Elrehim, O., Tayoun, A. A., Rehm, H. L., Amr, S. S. <strong>Recurrent variants in OTOF are significant contributors to prelingual nonsyndromic hearing loss in Saudi patients.</strong> Genet. Med. 20: 536-544, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29048421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29048421</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29048421[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/10.1038/gim.2017.143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29048421">Almontashiri et al. (2018)</a> identified homozygosity for a c.5375G-A transition in the OTOF gene that resulted in an arg1792-to-his (R1792H) amino acid substitution. <a href="#2" class="mim-tip-reference" title="Almontashiri, N. A. M., Alswaid, A., Oza, A., Al-Mazrou, K. A., Elrehim, O., Tayoun, A. A., Rehm, H. L., Amr, S. S. <strong>Recurrent variants in OTOF are significant contributors to prelingual nonsyndromic hearing loss in Saudi patients.</strong> Genet. Med. 20: 536-544, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29048421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29048421</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29048421[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/10.1038/gim.2017.143" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29048421">Almontashiri et al. (2018)</a> observed this variant in 1 of 252,426 alleles from non-Middle Eastern populations in the gnomAD database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29048421" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="Almontashiri2018" class="mim-anchor"></a>
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Almontashiri, N. A. M., Alswaid, A., Oza, A., Al-Mazrou, K. A., Elrehim, O., Tayoun, A. A., Rehm, H. L., Amr, S. S.
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<strong>Recurrent variants in OTOF are significant contributors to prelingual nonsyndromic hearing loss in Saudi patients.</strong>
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Genet. Med. 20: 536-544, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29048421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29048421</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29048421[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=29048421" 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/gim.2017.143" target="_blank">Full Text</a>]
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Chaib, H., Place, C., Salem, N., Chardenoux, S., Vincent, C., Weissenbach, J., El-Zir, E., Loiselet, J., Petit, C.
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[<a href="https://doi.org/10.1093/hmg/5.1.155" target="_blank">Full Text</a>]
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Choi, B. Y., Ahmed, Z. M., Riazuddin, S., Bhinder, M. A., Shahzad, M., Husnain, T., Riazuddin, S., Griffith, A. J., Friedman, T. B.
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<strong>Identities and frequencies of mutations of the otoferlin gene (OTOF) causing DFNB9 deafness in Pakistan.</strong>
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Clin. Genet. 75: 237-243, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19250381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19250381</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19250381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2008.01128.x" target="_blank">Full Text</a>]
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<a id="Dallol2016" class="mim-anchor"></a>
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Dallol, A., Daghistani, K., Elaimi, A., Al-Wazani, W. A., Bamanie, A., Safiah, M., Sagaty, S., Taha, L., Zahed, R., Bajouh, O., Chaudhary, A. G., Gari, M. A., Turki, R., Al-Qahtani, M. H., Abuzenadah, A. M.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27766948/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27766948</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27766948" 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/10.1186/s12881-016-0329-8" target="_blank">Full Text</a>]
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Heidrych, P., Zimmermann, U., Kuhn, S., Franz, C., Engel, J., Duncker, S. V., Hirt, B., Pusch, C. M., Ruth, P., Pfister, M., Marcotti, W., Blin, N., Knipper, M.
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[<a href="https://doi.org/10.1093/hmg/ddp213" target="_blank">Full Text</a>]
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<a id="Iwasa2022" class="mim-anchor"></a>
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Iwasa, Y., Nishio, S., Yoshimura, H., Sugaya, A., Kataoka, Y., Maeda, Y., Kanda, Y., Nagai, K., Naito, Y., Yamazaki, H., Ikezono, T., Matsuda, H., and 34 others.
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<strong>Detailed clinical features and genotype-phenotype correlation in an OTOF-related hearing loss cohort in Japan.</strong>
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Hum. Genet. 141: 865-875, 2022. Note: Erratum: Hum. Genet. 141: 993-995, 2022.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34536124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34536124</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34536124[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=34536124" 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/s00439-021-02351-7" target="_blank">Full Text</a>]
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<a id="Matsunaga2012" class="mim-anchor"></a>
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Matsunaga, T., Mutai, H., Kunishima, S., Namba, K., Morimoto, N., Shinjo, Y., Arimoto, Y., Kataoka, Y., Shintani, T., Morita, N., Sugiuchi, T., Masuda, S., Nakano, A., Taiji, H., Kaga, K.
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<strong>A prevalent founder mutation and genotype-phenotype correlations of OTOF in Japanese patients with auditory neuropathy.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22575033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22575033</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22575033" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2012.01897.x" target="_blank">Full Text</a>]
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<a id="Migliosi2002" class="mim-anchor"></a>
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Migliosi, V., Modamio-Hoybjor, S., Moreno-Pelayo, M. A., Rodriguez-Ballesteros, M., Villamar, M., Telleria, D., Menendez, I., Moreno, F., del Castillo, I.
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<strong>Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is frequently found in Spanish patients with prelingual non-syndromic hearing loss.</strong>
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J. Med. Genet. 39: 502-506, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12114484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12114484</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12114484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmg.39.7.502" target="_blank">Full Text</a>]
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<a id="10" class="mim-anchor"></a>
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<a id="Mirghomizadeh2002" class="mim-anchor"></a>
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Mirghomizadeh, F., Pfister, M., Apaydin, F., Petit, C., Kupka, S., Pusch, C. M., Zenner, H. P., Blin, N.
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<strong>Substitutions in the conserved C2C domain of otoferlin cause DFNB9, a form of nonsyndromic autosomal recessive deafness.</strong>
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Neurobiol. Dis. 10: 157-164, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12127154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12127154</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12127154" 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/nbdi.2002.0488" target="_blank">Full Text</a>]
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<a id="Rodriguez-Ballesteros2003" class="mim-anchor"></a>
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Rodriguez-Ballesteros, M., del Castillo, F. J., Martin, Y., Moreno-Pelayo, M. A., Morera, C., Prieto, F., Marco, J., Morant, A., Gallo-Teran, J., Morales-Angulo, C., Navas, C., Trinidad, G., Tapia, M. C., Moreno, F., del Castillo, I.
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<strong>Auditory neuropathy in patients carrying mutations in the otoferlin gene (OTOF).</strong>
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Hum. Mutat. 22: 451-456, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14635104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14635104</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14635104" 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/10.1002/humu.10274" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Rodriguez-Ballesteros2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Rodriguez-Ballesteros, M., Reynoso, R., Olarte, M., Villamar, M., Morera, C., Santarelli, R., Arslan, E., Meda, C., Curet, C., Volter, C., Sainz-Quevedo, M., Castorina, P., and 16 others.
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<strong>A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and auditory neuropathy.</strong>
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Hum. Mutat. 29: 823-831, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18381613/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18381613</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18381613" 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/10.1002/humu.20708" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Roux2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Roux, I., Safieddine, S., Nouvian, R., Grati, M., Simmler, M.-C., Bahloul, A., Perfettini, I., Le Gall, M., Rostaing, P., Hamard, G., Triller, A., Avan, P., Moser, T., Petit, C.
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<strong>Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse.</strong>
|
|
Cell 127: 277-289, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17055430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17055430</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17055430" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.cell.2006.08.040" target="_blank">Full Text</a>]
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</p>
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</li>
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Starr1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Starr, A., Sininger, Y., Winter, M., Derebery, M. J., Oba, S., Michalewski, H. J.
|
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<strong>Transient deafness due to temperature-sensitive auditory neuropathy.</strong>
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Ear Hear. 19: 169-179, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9657592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9657592</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9657592" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1097/00003446-199806000-00001" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="Tekin2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tekin, M., Akcayoz, D., Incesulu, A.
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<strong>A novel missense mutation in a C2 domain of OTOF results in autosomal recessive auditory neuropathy.</strong>
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Am. J. Med. Genet. 138A: 6-10, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16097006/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16097006</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16097006" 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/10.1002/ajmg.a.30907" target="_blank">Full Text</a>]
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<a id="16" class="mim-anchor"></a>
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<a id="Varga2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Varga, R., Avenarius, M. R., Kelley, P. M., Keats, B. J., Berlin, C. I., Hood, L. J., Morlet, T. G., Brashears, S. M., Starr, A., Cohn, E. S., Smith, R. J. H., Kimberling, W. J.
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<strong>OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele.</strong>
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J. Med. Genet. 43: 576-581, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16371502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16371502</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16371502" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmg.2005.038612" target="_blank">Full Text</a>]
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<li>
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<a id="17" class="mim-anchor"></a>
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<a id="Varga2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Varga, R., Kelley, P. M., Keats, B. J., Starr, A., Leal, S. M., Cohn, E., Kimberling, W. J.
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<strong>Non-syndromic recessive auditory neuropathy is the result of mutations in the otoferlin (OTOF) gene (Letter)</strong>
|
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J. Med. Genet. 40: 45-50, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12525542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12525542</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12525542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmg.40.1.45" target="_blank">Full Text</a>]
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<li>
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<a id="18" class="mim-anchor"></a>
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<a id="Yasunaga2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yasunaga, S., Grati, M., Chardenoux, S., Smith, T. N., Friedman, T. B., Lalwani, A. K., Wilcox, E. R., Petit, C.
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<strong>OTOF encodes multiple long and short isoforms: genetic evidence that the long ones underlie recessive deafness DFNB9.</strong>
|
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Am. J. Hum. Genet. 67: 591-600, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10903124/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10903124</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10903124[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=10903124" 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/10.1086/303049" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="19" class="mim-anchor"></a>
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<a id="Yasunaga1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yasunaga, S., Grati, M., Cohen-Salmon, M., El-Amraoui, A., Mustapha, M., Salem, N., El-Zir, E., Loiselet, J., Petit, C.
|
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<strong>A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness.</strong>
|
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Nature Genet. 21: 363-369, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10192385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10192385</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10192385" 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/10.1038/7693" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="20" class="mim-anchor"></a>
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<a id="Yasunaga2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yasunaga, S., Petit, C.
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<strong>Physical map of the region surrounding the otoferlin locus on chromosome 2p22-p23.</strong>
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Genomics 66: 110-112, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10843812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10843812</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10843812" 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.2000.6185" target="_blank">Full Text</a>]
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</p>
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</div>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Sonja A. Rasmussen - updated : 07/29/2022
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
|
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Ada Hamosh - updated : 08/31/2018<br>Cassandra L. Kniffin - updated : 2/26/2013<br>Marla J. F. O'Neill - updated : 3/13/2012<br>George E. Tiller - updated : 6/23/2010<br>Stylianos E. Antonarakis - updated : 3/20/2007<br>Victor A. McKusick - updated : 9/13/2006<br>Cassandra L. Kniffin - updated : 9/16/2005<br>Victor A. McKusick - updated : 1/12/2004<br>Cassandra L. Kniffin - updated : 12/9/2003<br>Cassandra L. Kniffin - updated : 11/13/2003<br>Victor A. McKusick - updated : 3/12/2003<br>Victor A. McKusick - updated : 11/1/2000<br>Victor A. McKusick - updated : 9/22/2000<br>Paul J. Converse - updated : 7/7/2000
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh : 3/29/1999
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 07/29/2022
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 09/05/2018<br>carol : 09/04/2018<br>alopez : 08/31/2018<br>joanna : 04/28/2015<br>alopez : 4/22/2015<br>mcolton : 4/16/2015<br>carol : 3/4/2013<br>ckniffin : 2/26/2013<br>carol : 3/15/2012<br>terry : 3/13/2012<br>wwang : 7/1/2010<br>terry : 6/23/2010<br>carol : 8/4/2009<br>carol : 9/11/2007<br>mgross : 3/20/2007<br>alopez : 2/4/2007<br>alopez : 9/15/2006<br>alopez : 9/15/2006<br>terry : 9/13/2006<br>carol : 10/5/2005<br>wwang : 9/30/2005<br>ckniffin : 9/16/2005<br>terry : 3/3/2005<br>carol : 12/30/2004<br>carol : 12/30/2004<br>cwells : 1/15/2004<br>terry : 1/12/2004<br>carol : 12/12/2003<br>ckniffin : 12/9/2003<br>tkritzer : 11/18/2003<br>tkritzer : 11/18/2003<br>ckniffin : 11/13/2003<br>carol : 4/1/2003<br>tkritzer : 3/25/2003<br>terry : 3/12/2003<br>alopez : 2/21/2001<br>mcapotos : 11/8/2000<br>mcapotos : 11/7/2000<br>terry : 11/1/2000<br>mcapotos : 10/5/2000<br>mcapotos : 9/28/2000<br>mcapotos : 9/28/2000<br>terry : 9/22/2000<br>mgross : 7/7/2000<br>alopez : 3/24/2000<br>carol : 3/30/1999<br>alopez : 3/30/1999<br>alopez : 3/29/1999<br>alopez : 3/29/1999
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
|
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<span class="mim-font">
|
|
<strong>*</strong> 603681
|
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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OTOFERLIN; OTOF
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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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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: OTOF</em></strong>
|
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
|
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<em>
|
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Cytogenetic location: 2p23.3
|
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 2:26,457,203-26,558,756 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</h4>
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<div>
|
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
|
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
|
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</th>
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<th>
|
|
Inheritance
|
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</th>
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<th>
|
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="2">
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<span class="mim-font">
|
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2p23.3
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</span>
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</td>
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<td>
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<span class="mim-font">
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|
Auditory neuropathy, autosomal recessive, 1
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|
</span>
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</td>
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<td>
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<span class="mim-font">
|
|
601071
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
|
Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
3
|
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
|
|
Deafness, autosomal recessive 9
|
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
601071
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
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<td>
|
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<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
|
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>TEXT</strong>
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</span>
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</h4>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>Cloning and Expression</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>Using a candidate gene approach in the critical region of chromosome 2p23.1 for a form of nonsyndromic deafness (DFNB9; 601071), Yasunaga et al. (1999) identified a novel human gene, which they called OTOF. ESTs in this region were submitted to rounds of 5-prime RACE-PCR and the deduced amino acids were compared with clones isolated from 2 subtracted mouse cochlear cDNA libraries. The human OTOF gene encodes a 4,954-bp transcript with a 3,690-bp open reading frame and a 1,038-bp 3-prime untranslated region with a polyadenylation signal at position 4934. The deduced 1,230-amino acid protein has a calculated molecular mass of 140.5 kD. It has 3 C2 domains and a single carboxy-terminal transmembrane domain. The protein is homologous to the C. elegans spermatogenesis factor FER-1 and human dysferlin (603009), prompting the authors to name it 'otoferlin.' The homology suggests the otoferlin is involved in vesicle membrane fusion. Otof expression was identified by RT-PCR in mouse cochlea, vestibule, and brain. By in situ hybridization, Otof labeling was seen in the inner hair cells, and faintly in the outer hair cells and spiral ganglion cells, at embryonic day 19.5, P0, and P2. Neuroepithelia of the utricle, saccule, and semicircular canals expressed Otof during the same days. Type I cells, but not type II cells or supporting cells, expressed Otof. </p><p>By Northern blot analysis, Yasunaga et al. (2000) detected a 7-kb otoferlin mRNA in the human brain. They isolated a corresponding cDNA, which was predicted to encode a 1,977-long form of otoferlin with 6 C2 domains. Other alternatively spliced transcripts were detected, which predicted several long isoforms (with 6 C2 domains) in humans and mice and short isoforms (3 C2 domains) only in humans. </p><p>Choi et al. (2009) demonstrated the existence of an alternative splice isoform of OTOF expressed in the human cochlea, and observed that human cochlear transcripts exclusively used exon 48 to encode the C-terminal 60 amino acids of this isoform, which lacks exon 47. The authors concluded that this isoform must be required for human hearing because it encodes a unique alternative C terminus affected by some DFNB9 mutations. </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>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</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>Yasunaga et al. (1999) found that the OTOF gene extends over 21 kb and contains at least 28 coding exons, a 5-prime UTR exon, and a 3-prime UTR exon. </p><p>Yasunaga et al. (2000) found that the OTOF gene contains 48 coding exons and spans approximately 90 kb. </p>
|
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</span>
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<div>
|
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>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">
|
|
<p>By analysis of a contig containing 8 YACs, 12 BACs, and 4 PACs, Yasunaga and Petit (2000) refined the mapping of OTOF and its surrounding genes on 2p23-p22. The authors oriented the 5-prime region of OTOF as centromeric. </p>
|
|
</span>
|
|
<div>
|
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<br />
|
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<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>Roux et al. (2006) showed that otoferlin expression in mouse hair cells correlated with afferent synaptogenesis, and they found that otoferlin localized to ribbon-associated synaptic vesicles. Otoferlin bound Ca(2+) and displayed Ca(2+)-dependent interactions with the SNARE proteins syntaxin-1 (STX1A; 186590) and SNAP25 (600322). </p><p>Otoferlin has been proposed to be the calcium sensor in hair cell exocytosis, compensating for the classic synaptic fusion proteins synaptotagmin-1 (SYT1; 185605) and synaptotagmin-2 (SYT2; 600104). Heidrych et al. (2009) demonstrated in a yeast 2-hybrid assay that myosin VI (MYO6; 600970) is a novel otoferlin-binding partner. Coimmunoprecipitation assay and coexpression suggested an interaction of both proteins within the basolateral part of inner hair cells (IHCs). Comparison of Otof-mutant and Myo6-mutant mice indicated noncomplementary and complementary roles of myosin VI and otoferlin for synaptic maturation. IHCs from Otof-mutant mice exhibited a decoupling of Ctbp2 (602619) and CaV1.3 (CACNA1D; 114206) and severe reduction of exocytosis. Myo6-mutant IHCs failed to transport BK channels to the membrane of the apical cell regions, and the exocytotic Ca(2+) efficiency did not mature, and Otof- and Myo6-mutant IHCs showed a reduced basolateral synaptic surface area and altered active zone topography. Membrane infoldings in Otof-mutant inner hair cells indicated disturbed transport of endocytotic membranes and linked the above morphologic changes to a complementary role of otoferlin and myosin VI in transport of intracellular compartments to the basolateral inner hair cell membrane. </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>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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|
|
|
|
<span class="mim-text-font">
|
|
<p>Yasunaga et al. (1999) identified a nonsense mutation (tyr703 to ter; 603681.0001) in the OTOF gene in all affected members of 4 unrelated Lebanese families. </p><p>Yasunaga et al. (2000) studied a consanguineous family originating from India in which 3 sibs suffered from severe to profound hearing loss. By segregation analysis with polymorphic markers of the DFNB9 chromosomal region, they concluded that an OTOF mutation was likely to underlie deafness in this family. By sequencing the 48 OTOF coding exons in members of this family, they identified a splice mutation in intron 8 (603681.0002). These studies demonstrated that the long otoferlin isoforms are required for inner ear function. </p><p>Adato et al. (2000) studied the molecular basis of hearing impairment in 4 Druze families from the same village in northern Galilee. The Druze are a small, isolated population practicing endogamous marriage. Thus it was expected that a single mutation would account for hearing impairment in all these families. The results, however, showed that at least 4 different genes were involved. One was a new mutation in the OTOF gene (603681.0003), the second was a mutation in the SLC26A4 gene (thr193 to ile; 605646.0019), and the third was a 35delG mutation in the GJB2 gene (121011.0005). In the fourth family, linkage was excluded from all known hearing impairment loci (recessive and dominant), as well as from markers covering chromosomes 11 through 22, pointing therefore to the existence of another nonsyndromic recessive hearing loss locus on chromosomes 1 through 10. </p><p>In 1 Cuban family, 2 Spanish families, and 8 sporadic Spanish patients with nonsyndromic sensorineural hearing loss, Migliosi et al. (2002) identified a gln829-to-ter mutation in exon 22 of the OTOF gene (Q829X; 603681.0004). Migliosi et al. (2002) determined that the Q829X mutation was responsible for 4.4% of recessive familial or sporadic cases of deafness in the Spanish population, and presented evidence for a founder effect. </p><p>Rodriguez-Ballesteros et al. (2003) extended the screening for the Q829X mutation to 289 additional unrelated families, finding 15 new cases, 9 of which were homozygous and 6 of which were heterozygous. All of them had a mode of inheritance compatible with an autosomal recessive pattern. Four previously undescribed mutations were identified. A total of 37 subjects with mutations in OTOF were studied clinically. They were phenotypically homogeneous, having profound hearing impairment with very early onset, as shown by pure-tone audiometry and auditory brainstem responses. No inner ear malformation was demonstrated by MRI and CT. Cochlear implants had been successfully provided in 10 subjects. They found that transient evoked otoacoustic emissions (TEOAEs) were present, either bilaterally or unilaterally, in 11 subjects. This raises questions about universal screening programs that use TEOAEs as the first detection test for hearing impairment in newborns, since this technique may overlook a nonnegligible proportion of cases. </p><p>Almontashiri et al. (2018) screened 33 Saudi hearing loss probands for mutations in hearing loss genes and identified mutations in 21 probands. One of 2 mutations in the OTOF gene, glu57-to-ter (603681.0014) and arg1792-to-his (603681.0015), was present in one-third of these individuals (7/21). Only 1 of the 33 probands had a homozygous GJB6 (604418) deletion, and no sequence variants were detected in GJB2 (121011). </p>
|
|
</span>
|
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<div>
|
|
<br />
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</div>
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|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Matsunaga et al. (2012) identified an R1939Q (603681.0012) mutation in the OTOF gene, in 13 (56.5%) of 23 Japanese patients with early-onset auditory neuropathy. Seven patients were homozygous for the mutation, 4 were compound heterozygous for R1939Q and a truncating or splice site mutation in OTOF, 1 was compound heterozygous for R1939Q and a nontruncating mutation in OTOF, and 1 was heterozygous for the R1939Q mutation. Haplotype analysis indicated a founder effect for the R1939Q mutation. Those who were homozygous for R1939Q or compound heterozygous for R1939Q and a truncating mutation had a consistent and severe phenotype, whereas the patient who was compound heterozygous for R1939Q and a nontruncating mutation had a less severe phenotype, with moderate hearing loss at age 29 years and sloping audiograms. The findings suggested that the R1939Q variant likely causes a severe impairment of protein function, and that, in general, truncating mutations cause a more severe phenotype than nontruncating mutations. </p><p>Among 64 patients with OTOF-related hearing loss from a large Japanese database, Iwasa et al. (2022) found that all 27 patients homozygous for the R1939Q mutation, as well as 22 compound heterozygotes for R1939Q and a truncating mutation and 1 patient with 2 truncating mutations, showed profound hearing loss. Among patients with one or more nontruncating mutations other than R1939Q, almost half had mild to moderate hearing loss. The genotype-phenotype correlation in nontruncating mutations was unclear, with the same mutation sometimes causing different phenotypes. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Roux et al. (2006) found that Otof -/- mice were profoundly deaf. Exocytosis in Otof -/- auditory inner hair cells was almost completely abolished, despite normal ribbon synapse morphogenesis and Ca(2+) current. Roux et al. (2006) concluded that OTOF is essential for a late step of synaptic vesicle exocytosis and may act as the major Ca(2+) sensor triggering membrane fusion at the auditory inner hair cell ribbon synapse. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
|
|
|
|
</div>
|
|
|
|
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|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>15 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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|
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|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 DEAFNESS, AUTOSOMAL RECESSIVE 9</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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|
|
|
OTOF, TYR730TER
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<br />
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|
|
SNP: rs80356600,
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|
|
ClinVar: RCV000006507, RCV000219111, RCV005055505
|
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</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In members of 4 unrelated Lebanese families (F, AB, K1, and K2) of disparate geographic origin affected with autosomal recessive deafness-9 (DFNB9; 601071), Yasunaga et al. (1999) identified a homozygous T-to-A transversion at position 2416 in exon 18 of the OTOF gene, causing a tyr-to-stop substitution at codon 730. The mutation was not identified in 106 unrelated, unaffected individuals living in Lebanon. Family F was originally reported by Chaib et al. (1996). </p>
|
|
</span>
|
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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>
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|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 DEAFNESS, AUTOSOMAL RECESSIVE 9</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
OTOF, IVS8AS, A-G, -2
|
|
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|
|
<br />
|
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|
|
SNP: rs80356584,
|
|
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|
|
|
|
|
ClinVar: RCV000006508, RCV003698743
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family from southwestern India, Yasunaga et al. (2000) showed that deafness (DFNB9; 601071) was due to homozygosity for an A-to-G transition at the intron 8/exon 9 junction (IVS8-2A-G) of the OTOF gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 DEAFNESS, AUTOSOMAL RECESSIVE 9</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
OTOF, IVS5, G-A, +1
|
|
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|
|
<br />
|
|
|
|
SNP: rs2148047884,
|
|
|
|
|
|
|
|
ClinVar: RCV000006509
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Adato et al. (2000) found that nonsyndromic deafness (DFNB9; 601071) in a Druze family was due to homozygosity for a G-to-A transition at position +1, the first intronic nucleotide in the splice donor site of exon 5. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 DEAFNESS, AUTOSOMAL RECESSIVE 9</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
OTOF, GLN829TER
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|
|
<br />
|
|
|
|
SNP: rs80356593,
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|
|
|
gnomAD: rs80356593,
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|
|
|
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ClinVar: RCV000006511, RCV000211838, RCV000325939, RCV002227998, RCV004751204
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Among 28 unrelated Spanish families with nonsyndromic sensorineural hearing loss (601071), Migliosi et al. (2002) identified 1 family with a mutation in the OTOF gene: a 2485C-T transition in exon 22, resulting in a premature stop codon, gln829 to ter (Q829X). Both parents were carriers of the mutation and their 2 affected children were homozygous. The mutation was not present in 200 unrelated Spanish controls with normal hearing. Genetic analysis of another 269 unrelated patients with hearing loss revealed 11 more cases (8 sporadic and 3 familial) of the Q829X mutation. One of these families was compound heterozygous for Q829X and P1825A (603681.0005). Migliosi et al. (2002) determined that the Q829X mutation was responsible for 4.4% of recessive familial or sporadic cases of deafness in the Spanish population, and presented evidence for a founder effect. </p><p>Varga et al. (2006) found the Q829X mutation in 2 families. They referred to Q829X as the Hispanic mutation, it having been found in a group of Spanish families and 1 Cuban family as noted. They described it in a family from England with no known Hispanic ancestry. In a family of Mexican ancestry, the Q829X mutation was present in heterozygous state. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
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</div>
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</div>
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<div>
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 DEAFNESS, AUTOSOMAL RECESSIVE 9</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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|
|
|
OTOF, PRO1825ALA
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|
|
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|
<br />
|
|
|
|
SNP: rs28937591,
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|
|
|
|
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ClinVar: RCV000006512
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|
|
|
|
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</span>
|
|
</div>
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|
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Spanish family with sensorineural hearing loss (601071), Migliosi et al. (2002) identified compound heterozygosity for mutations in the OTOF gene: a 5473C-G transversion in exon 44, resulting in a pro1825-to-ala (P1825A) substitution, and Q829X (603681.0004). The authors noted that P1825A was the first missense mutation identified in the OTOF gene, and that it alters a conserved residue in the sixth C2 domain of the long isoforms, a domain expected to bind calcium. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 AUDITORY NEUROPATHY, AUTOSOMAL RECESSIVE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
|
|
|
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OTOF, 1-BP DEL, 1778G
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|
|
|
|
|
<br />
|
|
|
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SNP: rs80356587,
|
|
|
|
|
|
gnomAD: rs80356587,
|
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|
|
|
|
ClinVar: RCV000021037, RCV002293239, RCV004589519
|
|
|
|
|
|
</span>
|
|
</div>
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|
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with nonsyndromic recessive auditory neuropathy (see 601071) characterized by hearing loss with normal function of the outer hair cells, Varga et al. (2003) identified compound heterozygosity for mutations in the OTOF gene: a 1-bp deletion (1778G) in exon 16, leading to a stop codon, and a 6141G-A change, resulting in an arg-to-gln substitution in exon 48 (603681.0007). </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
|
|
</div>
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|
|
|
</div>
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|
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|
<div>
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 AUDITORY NEUROPATHY, AUTOSOMAL RECESSIVE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
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<span class="mim-text-font">
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OTOF, 6141G-A
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<br />
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|
|
SNP: rs80356605,
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|
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|
|
|
gnomAD: rs80356605,
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|
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|
|
|
ClinVar: RCV000006510, RCV000021073, RCV003480023
|
|
|
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|
|
</span>
|
|
</div>
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|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 6141G-A change in the OTOF gene that was found in compound heterozygous state in patients with nonsyndromic recessive auditory neuropathy (see 601071) by Varga et al. (2003), see 603681.0006. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
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|
</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 AUDITORY NEUROPATHY, AUTOSOMAL RECESSIVE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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|
|
<div>
|
|
<span class="mim-text-font">
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|
|
|
OTOF, IVS39, +1, G-C
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<br />
|
|
|
|
SNP: rs80356602,
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|
|
ClinVar: RCV000006514, RCV000021068
|
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|
|
</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with nonsyndromic recessive auditory neuropathy (see 601071) characterized by hearing loss with normal function of the outer hair cells, Varga et al. (2003) identified a heterozygous G-C transversion in the donor splice site of intron 39, which is predicted to result in a truncated protein. </p>
|
|
</span>
|
|
</div>
|
|
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|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 AUDITORY NEUROPATHY, AUTOSOMAL RECESSIVE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
OTOF, PRO50ARG
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|
<br />
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|
|
SNP: rs121908598,
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|
|
|
|
|
|
|
ClinVar: RCV000006515
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with nonsyndromic recessive auditory neuropathy (see 601071) characterized by hearing loss with normal function of the outer hair cells, Varga et al. (2003) identified a heterozygous 6285C-G change in the OTOF gene, resulting in a pro50-to-arg (P50R) substitution. </p>
|
|
</span>
|
|
</div>
|
|
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|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 AUDITORY NEUROPATHY, AUTOSOMAL RECESSIVE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
OTOF, LEU1011PRO
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|
|
|
|
|
<br />
|
|
|
|
SNP: rs80356596,
|
|
|
|
|
|
|
|
ClinVar: RCV000006516, RCV000021054
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 Turkish sibs with nonsyndromic recessive auditory neuropathy (see 601071), Tekin et al. (2005) identified a homozygous 3032T-C transition in exon 26 of the OTOF gene, resulting in a leu1011-to-pro (L1011P) substitution in the fourth C2 domain (C2D) of the protein. The consanguineous parents were heterozygous for the mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 AUDITORY NEUROPATHY, AUTOSOMAL RECESSIVE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
AUDITORY NEUROPATHY, AUTOSOMAL RECESSIVE, 1, TEMPERATURE-SENSITIVE, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
OTOF, ILE515THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80356586,
|
|
|
|
|
|
gnomAD: rs80356586,
|
|
|
|
|
|
ClinVar: RCV000006517, RCV000021035, RCV000604852, RCV003555942
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Mirghomizadeh et al. (2002) described a consanguineous family from eastern Turkey in which members had profound prelingual hearing loss (see 601071) and a 1544T-C transition in the OTOF gene causing an ile515-to-thr (I515T) substitution. Affected members of the family were homozygous for the I515T mutation and a second missense mutation, inherited in cis. Both mutations were in the C2C domain (third C2 domain), which is predicted to bind calcium. The alignment of otoferlin and otoferlin-related proteins revealed remarkable conservation of amino acids within the human and mouse C2C domains. Mirghomizadeh et al. (2002) predicted that either of the 2 mutations would severely disrupt the structure of the C2C domain, with the I515T mutation resulting in the creation of a new myristylation site. </p><p>Varga et al. (2006) reported the I515T mutation in heterozygous state in an individual who was observed to be temperature-sensitive for the auditory neuropathy phenotype (see 601071). In the family reported by Starr et al. (1998), Varga et al. (2006) found that the proband had abnormal auditory brainstem response (ABR), present otoacoustic emissions (OAE), and relatively normal hearing until she became febrile, when OAE remained normal but hearing degraded, and ABR worsened from abnormal with unidentified waves I-III and delayed latency of the wave IV-V complex to being totally absent. The amount of decline in hearing in the proband was dependent on the degree of fever. A mild to moderate hearing loss was present when she had the temperature of 37.8 degrees centigrade and profound hearing loss was present at 38.1 degrees centigrade. The proband's brother, who also carried the mutation, experienced similar hearing loss when febrile. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 AUDITORY NEUROPATHY, AUTOSOMAL RECESSIVE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
OTOF, ARG1939GLN
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000006510, RCV000021073, RCV003480023
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 13 (56.5%) of 23 Japanese patients with early-onset auditory neuropathy (see 601071), Matsunaga et al. (2012) identified a 5816G-A transition in exon 50 of the OTOF gene, resulting in an arg1939-to-gln (R1939Q) substitution. Seven patients were homozygous for the mutation, 4 were compound heterozygous for R1939Q and a truncating or splice site mutation in OTOF, 1 was compound heterozygous for R1939Q and a nontruncating mutation in OTOF, and 1 was heterozygous for the R1939Q mutation. Haplotype analysis indicated a founder effect for the R1939Q mutation. The R1939Q mutation was found in 1 of 189 control individuals. Those who were homozygous for R1939Q or compound heterozygous for R1939Q and a truncating mutation had a consistent and severe phenotype, whereas the patient who was compound heterozygous for R1939Q and a nontruncating mutation had a less severe phenotype, with moderate hearing loss at age 29 years and sloping audiograms. </p><p>Among the 64 patients with DFNB9 identified in a large Japanese database, Iwasa et al. (2022) found that 27 (42%) were homozygous for the R1939Q variant, and 29 (45%) were compound heterozygous for the R1939Q variant and another mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 AUDITORY NEUROPATHY, AUTOSOMAL RECESSIVE, 1, TEMPERATURE-SENSITIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
OTOF, GLY541SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397515435,
|
|
|
|
|
|
gnomAD: rs397515435,
|
|
|
|
|
|
ClinVar: RCV000033199
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 26-year-old Japanese man, born of consanguineous parents, with temperature-sensitive auditory neuropathy (see 601071), Matsunaga et al. (2012) identified a homozygous 1621G-A transition in exon 15 of the OTOF gene, resulting in a gly541-to-ser (G541S) substitution that was specific to the long isoform. The mutation was not found in 376 control individuals. The patient complained of difficulty in understanding conversation and reported that his hearing deteriorated when he became febrile or was exposed to loud noise. Pure-tone audiometry when he was afebrile revealed mild hearing loss with a flat configuration. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 DEAFNESS, AUTOSOMAL RECESSIVE 9</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
OTOF, GLU747X ({dbSNP rs397515591})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397515591,
|
|
|
|
|
|
gnomAD: rs397515591,
|
|
|
|
|
|
ClinVar: RCV000056026, RCV000211840, RCV000318963, RCV003905022
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2-year-old child from a multiplex Libyan family with profound prelingual sensorineural hearing loss (DFNB9; 601071), Rodriguez-Ballesteros et al. (2008) detected homozygosity for a c.2239G-T transversion in exon 20 of the OTOF gene that resulted in a glu747-to-ter (E747X) amino acid substitution. The authors noted that the mutation affected both the long and the short isoforms of OTOF. </p><p>In a Saudi Arabian brother and sister with severe to profound hearing impairment, Dallol et al. (2016) identified homozygosity for a c.2239G-T transversion (c.2239G-T, NM_194248) in the OTOF gene that resulted in an E747X amino acid substitution. The mutation was identified by targeted sequencing of 87 genes known to be involved in hearing impairment, and confirmed by Sanger sequencing. </p><p>In 3 Saudi families (F-7, F-25, and F-27) with autosomal recessive prelingual sensorineural hearing loss, Almontashiri et al. (2018) identified homozygosity for the E747X mutation in the OTOF gene, which they designated c.169G-T (GLU57TER, E57X). The mutation was identified by targeted sequencing and confirmed by Sanger sequencing. Almontashiri et al. (2018) observed this variant in 1 of 251,632 alleles from non-Middle Eastern populations in the gnomAD database. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 DEAFNESS, AUTOSOMAL RECESSIVE 9</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
OTOF, ARG1792HIS ({dbSNP rs111033349})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs111033349,
|
|
|
|
|
|
gnomAD: rs111033349,
|
|
|
|
|
|
ClinVar: RCV000041571, RCV000171287, RCV000656336
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members from 4 (F-18, F-22, F-31, and F-32) of 33 Saudi families with autosomal recessive prelingual sensorineural hearing loss (DFNB9; 601071), Almontashiri et al. (2018) identified homozygosity for a c.5375G-A transition in the OTOF gene that resulted in an arg1792-to-his (R1792H) amino acid substitution. Almontashiri et al. (2018) observed this variant in 1 of 252,426 alleles from non-Middle Eastern populations in the gnomAD database. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Adato, A., Raskin, L., Petit, C., Bonne-Tamir, B.
|
|
<strong>Deafness heterogeneity in a Druze isolate from the Middle East: novel OTOF and PDS mutations, low prevalence of GJB2 35delG mutation and indication for a new DFNB locus.</strong>
|
|
Europ. J. Hum. Genet. 8: 437-442, 2000.
|
|
|
|
|
|
[PubMed: 10878664]
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|
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|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5200489]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Almontashiri, N. A. M., Alswaid, A., Oza, A., Al-Mazrou, K. A., Elrehim, O., Tayoun, A. A., Rehm, H. L., Amr, S. S.
|
|
<strong>Recurrent variants in OTOF are significant contributors to prelingual nonsyndromic hearing loss in Saudi patients.</strong>
|
|
Genet. Med. 20: 536-544, 2018.
|
|
|
|
|
|
[PubMed: 29048421]
|
|
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|
|
[Full Text: https://doi.org/10.1038/gim.2017.143]
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chaib, H., Place, C., Salem, N., Chardenoux, S., Vincent, C., Weissenbach, J., El-Zir, E., Loiselet, J., Petit, C.
|
|
<strong>A gene responsible for a sensorineural nonsyndromic recessive deafness maps to chromosome 2p22-23.</strong>
|
|
Hum. Molec. Genet. 5: 155-158, 1996.
|
|
|
|
|
|
[PubMed: 8789454]
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|
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|
|
|
[Full Text: https://doi.org/10.1093/hmg/5.1.155]
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|
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</p>
|
|
</li>
|
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Choi, B. Y., Ahmed, Z. M., Riazuddin, S., Bhinder, M. A., Shahzad, M., Husnain, T., Riazuddin, S., Griffith, A. J., Friedman, T. B.
|
|
<strong>Identities and frequencies of mutations of the otoferlin gene (OTOF) causing DFNB9 deafness in Pakistan.</strong>
|
|
Clin. Genet. 75: 237-243, 2009.
|
|
|
|
|
|
[PubMed: 19250381]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2008.01128.x]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dallol, A., Daghistani, K., Elaimi, A., Al-Wazani, W. A., Bamanie, A., Safiah, M., Sagaty, S., Taha, L., Zahed, R., Bajouh, O., Chaudhary, A. G., Gari, M. A., Turki, R., Al-Qahtani, M. H., Abuzenadah, A. M.
|
|
<strong>Utilization of amplicon-based targeted sequencing panel for the massively parallel sequencing of sporadic hearing impairment patients from Saudi Arabia.</strong>
|
|
BMC Med. Genet. 17: 67, 2016. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 27766948]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1186/s12881-016-0329-8]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Heidrych, P., Zimmermann, U., Kuhn, S., Franz, C., Engel, J., Duncker, S. V., Hirt, B., Pusch, C. M., Ruth, P., Pfister, M., Marcotti, W., Blin, N., Knipper, M.
|
|
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Rodriguez-Ballesteros, M., del Castillo, F. J., Martin, Y., Moreno-Pelayo, M. A., Morera, C., Prieto, F., Marco, J., Morant, A., Gallo-Teran, J., Morales-Angulo, C., Navas, C., Trinidad, G., Tapia, M. C., Moreno, F., del Castillo, I.
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Rodriguez-Ballesteros, M., Reynoso, R., Olarte, M., Villamar, M., Morera, C., Santarelli, R., Arslan, E., Meda, C., Curet, C., Volter, C., Sainz-Quevedo, M., Castorina, P., and 16 others.
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<strong>A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and auditory neuropathy.</strong>
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Roux, I., Safieddine, S., Nouvian, R., Grati, M., Simmler, M.-C., Bahloul, A., Perfettini, I., Le Gall, M., Rostaing, P., Hamard, G., Triller, A., Avan, P., Moser, T., Petit, C.
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<strong>Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse.</strong>
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Starr, A., Sininger, Y., Winter, M., Derebery, M. J., Oba, S., Michalewski, H. J.
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<strong>A novel missense mutation in a C2 domain of OTOF results in autosomal recessive auditory neuropathy.</strong>
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Varga, R., Avenarius, M. R., Kelley, P. M., Keats, B. J., Berlin, C. I., Hood, L. J., Morlet, T. G., Brashears, S. M., Starr, A., Cohn, E. S., Smith, R. J. H., Kimberling, W. J.
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<strong>Non-syndromic recessive auditory neuropathy is the result of mutations in the otoferlin (OTOF) gene (Letter)</strong>
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<strong>OTOF encodes multiple long and short isoforms: genetic evidence that the long ones underlie recessive deafness DFNB9.</strong>
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Yasunaga, S., Grati, M., Cohen-Salmon, M., El-Amraoui, A., Mustapha, M., Salem, N., El-Zir, E., Loiselet, J., Petit, C.
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<strong>A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness.</strong>
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Nature Genet. 21: 363-369, 1999.
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Yasunaga, S., Petit, C.
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<strong>Physical map of the region surrounding the otoferlin locus on chromosome 2p22-p23.</strong>
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