3752 lines
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Entry
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- *606844 - ALMS1 CENTROSOME AND BASAL BODY ASSOCIATED PROTEIN; ALMS1
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*606844</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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<a href="#description">Description</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="#geneFunction">Gene Function</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="#molecularGenetics">Molecular Genetics</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/606844">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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<div id="mimFloatingLinksMenu">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000116127;t=ENST00000613296" 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=7840" 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=606844" 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 class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000116127;t=ENST00000613296" 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_001378454,NM_015120" 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_001378454" 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=606844" 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=06023&isoform_id=06023_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/ALMS1" 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/20067381,20521001,30047718,32693320,34783277,62420306,62988821,110349786,119620134,119620135,119620136,119620137,119712139,751259018,1131739974,1131739976,1375381500,1809496305" 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/Q8TCU4" 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=7840" 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=ENSG00000116127;t=ENST00000613296" 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=ALMS1" 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=ALMS1" 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+7840" 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/ALMS1" 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:7840" 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/7840" 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=ENST00000613296.6&hgg_start=73385758&hgg_end=73609919&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:428" 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:428" 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://medlineplus.gov/genetics/gene/alms1" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=606844[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=606844[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/ALMS1/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/ENSG00000116127" 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=ALMS1" 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=ALMS1" 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=ALMS1" 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="http://www.euro-wabb.org/en/lovd-genetic-variation-database" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=ALMS1&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/PA24721" 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:428" 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://www.mousephenotype.org/data/genes/MGI:1934606" 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/ALMS1#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:1934606" 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/7840/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/OMIA002316/" 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=7840" 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://zfin.org/ZDB-GENE-030131-4837" 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=ALMS1&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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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 63702009<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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606844
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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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ALMS1 CENTROSOME AND BASAL BODY ASSOCIATED PROTEIN; ALMS1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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KIAA0328
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<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=ALMS1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ALMS1</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/2/364?start=-3&limit=10&highlight=364">2p13.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:73385758-73609919&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'})">2:73,385,758-73,609,919</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="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/2/364?start=-3&limit=10&highlight=364">
|
|
2p13.1
|
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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">
|
|
Alstrom syndrome
|
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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/203800"> 203800 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<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">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/606844" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/606844" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>ALMS1 localizes to the centrosome and appears to have a role in centriole structure and function (<a href="#6" class="mim-tip-reference" title="Knorz, V. J., Spalluto, C., Lessard, M., Purvis, T. L., Adigun, F. F., Collin, G. B., Hanley, N. A., Wilson, D. I., Hearn, T. <strong>Centriolar association of ALMS1 and likely centrosomal functions of the ALMS motif-containing proteins C10orf90 and KIAA1731.</strong> Molec. Biol. Cell 21: 3617-3629, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20844083/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20844083</a>] [<a href="https://doi.org/10.1091/mbc.E10-03-0246" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20844083">Knorz et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20844083" 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 sequencing clones obtained from a size-fractionated brain cDNA library, <a href="#11" class="mim-tip-reference" title="Nagase, T., Ishikawa, K., Nakajima, D., Ohira, M., Seki, N., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.</strong> DNA Res. 4: 141-150, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9205841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9205841</a>] [<a href="https://doi.org/10.1093/dnares/4.2.141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9205841">Nagase et al. (1997)</a> cloned ALMS1, which they designated KIAA0328. The transcript contains a repetitive sequence at its 3-prime UTR. RT-PCR detected low expression in testis and little to no expression in all other tissues examined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9205841" 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 linkage mapping and scrutiny of positional candidate genes, <a href="#4" class="mim-tip-reference" title="Collin, G. B., Marshall, J. D., Ikeda, A., So, W. V., Russell-Eggitt, I., Maffei, P., Beck, S., Boerkoel, C. F., Sicolo, N., Martin, M., Nishina, P. M., Naggert, J. K. <strong>Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome.</strong> Nature Genet. 31: 74-78, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941369</a>] [<a href="https://doi.org/10.1038/ng867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11941369">Collin et al. (2002)</a> identified an uncharacterized transcript, KIAA0328, in which sequence variations were found to segregate with Alstrom syndrome (ALMS; <a href="/entry/203800">203800</a>). By aligning KIAA0328 with overlapping transcripts from several sequence databases, they obtained a full-length cDNA sequence of 12,871 basepairs with an open reading frame of 4,169 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11941369" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Hearn, T., Renforth, G. L., Spalluto, C., Hanley, N. A., Piper, K., Brickwood, S., White, C., Connolly, V., Taylor, J. F. N., Russell-Eggitt, I., Bonneau, D., Walker, M., Wilson, D. I. <strong>Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alstrom syndrome.</strong> Nature Genet. 31: 79-83, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941370</a>] [<a href="https://doi.org/10.1038/ng874" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11941370">Hearn et al. (2002)</a> studied a unique patient with a familial balanced reciprocal translocation involving 2p13 in which the KIAA0328 gene was disrupted by the translocation and the other copy disrupted by an intragenic mutation to cause Alstrom syndrome. By RT-PCR with exon prediction and specific primer design, they identified an ALMS1 sequence containing an open reading frame of 12.5 kb that encodes a protein of 4,169 amino acids. The protein contains a large tandem-repeat domain comprising 34 imperfect repetitions of 47 amino acids. <a href="#5" class="mim-tip-reference" title="Hearn, T., Renforth, G. L., Spalluto, C., Hanley, N. A., Piper, K., Brickwood, S., White, C., Connolly, V., Taylor, J. F. N., Russell-Eggitt, I., Bonneau, D., Walker, M., Wilson, D. I. <strong>Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alstrom syndrome.</strong> Nature Genet. 31: 79-83, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941370</a>] [<a href="https://doi.org/10.1038/ng874" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11941370">Hearn et al. (2002)</a> stated that their identification of the ALMS1 gene using cloning of the breakpoint of a balanced translocation represented the first use of this strategy to identify a gene involved in a recessive disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11941370" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using real-time PCR of mouse tissues, <a href="#7" class="mim-tip-reference" title="Li, G., Vega, R., Nelms, K., Gekakis, N., Goodnow, C., McNamara, P., Wu, H., Hong, N. A., Glynne, R. <strong>A role for Alstrom syndrome protein, Alms1, in kidney ciliogenesis and cellular quiescence.</strong> PLoS Genet. 3: e8, 2007. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17206865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17206865</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17206865[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1371/journal.pgen.0030008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17206865">Li et al. (2007)</a> detected highest Alms1 expression in testis. Expression was moderate in brain, eye, lung, and olfactory bulb and low in spleen, liver, and kidney. Immunohistochemical analysis localized Alms1 to the base of cilia in cultured mouse kidney cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17206865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Knorz, V. J., Spalluto, C., Lessard, M., Purvis, T. L., Adigun, F. F., Collin, G. B., Hanley, N. A., Wilson, D. I., Hearn, T. <strong>Centriolar association of ALMS1 and likely centrosomal functions of the ALMS motif-containing proteins C10orf90 and KIAA1731.</strong> Molec. Biol. Cell 21: 3617-3629, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20844083/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20844083</a>] [<a href="https://doi.org/10.1091/mbc.E10-03-0246" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20844083">Knorz et al. (2010)</a> reported that the deduced 4,169-amino acid ALMS1 protein has an N-terminal stretch of 17 consecutive glu residues, followed by a tandem repeat domain, a putative leucine zipper, his-rich and ser-rich regions, and a C-terminal ALMS motif domain. Unlike many other centrosomal proteins, ALMS1 has limited potential to form coiled-coils. <a href="#6" class="mim-tip-reference" title="Knorz, V. J., Spalluto, C., Lessard, M., Purvis, T. L., Adigun, F. F., Collin, G. B., Hanley, N. A., Wilson, D. I., Hearn, T. <strong>Centriolar association of ALMS1 and likely centrosomal functions of the ALMS motif-containing proteins C10orf90 and KIAA1731.</strong> Molec. Biol. Cell 21: 3617-3629, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20844083/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20844083</a>] [<a href="https://doi.org/10.1091/mbc.E10-03-0246" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20844083">Knorz et al. (2010)</a> also described a splice variant of ALMS1 that includes exon 2, which introduces 42 additional residues. This variant is rarely expressed in humans. High-resolution immunofluorescence microscopy of hTERT-RPE1 cells detected ALMS1 at the proximal ends of centrioles and basal bodies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20844083" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#7" class="mim-tip-reference" title="Li, G., Vega, R., Nelms, K., Gekakis, N., Goodnow, C., McNamara, P., Wu, H., Hong, N. A., Glynne, R. <strong>A role for Alstrom syndrome protein, Alms1, in kidney ciliogenesis and cellular quiescence.</strong> PLoS Genet. 3: e8, 2007. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17206865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17206865</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17206865[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1371/journal.pgen.0030008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17206865">Li et al. (2007)</a> found that depletion of Alms1 by short interfering RNA in mouse inner medullary collecting duct cells caused defective ciliogenesis. Alms1 knockdown did not affect transcription of ciliary genes, but cilia were stunted and mutant cells lacked the ability to increase calcium influx in response to mechanical stimuli. The stunted cilium phenotype was rescued by transfection of a cDNA encoding the N-terminal 1,282 amino acids of Alms1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17206865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using RNA interference, <a href="#6" class="mim-tip-reference" title="Knorz, V. J., Spalluto, C., Lessard, M., Purvis, T. L., Adigun, F. F., Collin, G. B., Hanley, N. A., Wilson, D. I., Hearn, T. <strong>Centriolar association of ALMS1 and likely centrosomal functions of the ALMS motif-containing proteins C10orf90 and KIAA1731.</strong> Molec. Biol. Cell 21: 3617-3629, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20844083/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20844083</a>] [<a href="https://doi.org/10.1091/mbc.E10-03-0246" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20844083">Knorz et al. (2010)</a> found that knockdown of ALMS1 in human cells reduced the intensity of CNAP1 (CEP2; <a href="/entry/609689">609689</a>) staining at the centrosome, increased the distance between centrioles, and caused a defect in trafficking of centriolar satellite PCM1 (<a href="/entry/600299">600299</a>)-positive granules. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20844083" 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="#4" class="mim-tip-reference" title="Collin, G. B., Marshall, J. D., Ikeda, A., So, W. V., Russell-Eggitt, I., Maffei, P., Beck, S., Boerkoel, C. F., Sicolo, N., Martin, M., Nishina, P. M., Naggert, J. K. <strong>Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome.</strong> Nature Genet. 31: 74-78, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941369</a>] [<a href="https://doi.org/10.1038/ng867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11941369">Collin et al. (2002)</a> and <a href="#5" class="mim-tip-reference" title="Hearn, T., Renforth, G. L., Spalluto, C., Hanley, N. A., Piper, K., Brickwood, S., White, C., Connolly, V., Taylor, J. F. N., Russell-Eggitt, I., Bonneau, D., Walker, M., Wilson, D. I. <strong>Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alstrom syndrome.</strong> Nature Genet. 31: 79-83, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941370</a>] [<a href="https://doi.org/10.1038/ng874" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11941370">Hearn et al. (2002)</a> identified 23 exons in the ALMS1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11941370+11941369" 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 radiation hybrid analysis, <a href="#11" class="mim-tip-reference" title="Nagase, T., Ishikawa, K., Nakajima, D., Ohira, M., Seki, N., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.</strong> DNA Res. 4: 141-150, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9205841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9205841</a>] [<a href="https://doi.org/10.1093/dnares/4.2.141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9205841">Nagase et al. (1997)</a> mapped the ALMS1 gene to chromosome 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9205841" 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>As a result of a linkage study in a large French Acadian kindred with Alstrom syndrome and because of evidence of founder effect, <a href="#3" class="mim-tip-reference" title="Collin, G. B., Marshall, J. D., Cardon, L. R., Nishina, P. M. <strong>Homozygosity mapping of Alstrom syndrome to chromosome 2p.</strong> Hum. Molec. Genet. 6: 213-219, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9063741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9063741</a>] [<a href="https://doi.org/10.1093/hmg/6.2.213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9063741">Collin et al. (1997)</a> were able to use homozygosity mapping to identify the Alstrom disease locus. In a genomewide screen, haplotype sharing for a region on chromosome 2 was observed in all affected individuals. Two-point linkage analysis resulted in a maximum lod score of 3.84 at theta = 0.00 for marker D2S292. By testing additional markers, the disease gene was localized to a 14.9-cM region on 2p14-p13 (see Figure 3 of <a href="#3" class="mim-tip-reference" title="Collin, G. B., Marshall, J. D., Cardon, L. R., Nishina, P. M. <strong>Homozygosity mapping of Alstrom syndrome to chromosome 2p.</strong> Hum. Molec. Genet. 6: 213-219, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9063741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9063741</a>] [<a href="https://doi.org/10.1093/hmg/6.2.213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9063741">Collin et al., 1997</a>). In a North African family in Algeria, <a href="#8" class="mim-tip-reference" title="Macari, F., Lautier, C., Girardet, A., Dadoun, F., Darmon, P., Dutour, A., Renard, E., Bouvagnet, P., Claustres, M., Oliver, C., Grigorescu, F. <strong>Refinement of genetic localization of the Alstrom syndrome on chromosome 2p12-13 by linkage analysis in a North African family.</strong> Hum. Genet. 103: 658-661, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9921899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9921899</a>] [<a href="https://doi.org/10.1007/s004390050887" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9921899">Macari et al. (1998)</a> refined the localization of the Alstrom syndrome locus to 2p13-p12, reducing the genetic interval to 6.1 cM. <a href="#2" class="mim-tip-reference" title="Collin, G. B., Marshall, J. D., Boerkoel, C. F., Levin, A. V., Weksberg, R., Greenberg, J., Michaud, J. L., Naggert, J. K., Nishina, P. M. <strong>Alstrom syndrome: further evidence for linkage to human chromosome 2p13.</strong> Hum. Genet. 105: 474-479, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10598815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10598815</a>] [<a href="https://doi.org/10.1007/s004390051133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10598815">Collin et al. (1999)</a> confirmed the mapping to 2p13 by performing a linkage study in 12 additional families. A maximum 2-point lod score of 7.13 (theta = 0.00) for marker D2S2110 and a maximum cumulative multipoint lod score of 9.16 for marker D2S2110 were observed. Meiotic recombination events localized the critical region containing the ALMS1 locus to a 6.1-cM interval flanked by markers D2S327 and D2S286. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9921899+10598815+9063741" 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="Collin, G. B., Marshall, J. D., Ikeda, A., So, W. V., Russell-Eggitt, I., Maffei, P., Beck, S., Boerkoel, C. F., Sicolo, N., Martin, M., Nishina, P. M., Naggert, J. K. <strong>Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome.</strong> Nature Genet. 31: 74-78, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941369</a>] [<a href="https://doi.org/10.1038/ng867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11941369">Collin et al. (2002)</a> and <a href="#5" class="mim-tip-reference" title="Hearn, T., Renforth, G. L., Spalluto, C., Hanley, N. A., Piper, K., Brickwood, S., White, C., Connolly, V., Taylor, J. F. N., Russell-Eggitt, I., Bonneau, D., Walker, M., Wilson, D. I. <strong>Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alstrom syndrome.</strong> Nature Genet. 31: 79-83, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941370</a>] [<a href="https://doi.org/10.1038/ng874" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11941370">Hearn et al. (2002)</a> cloned the ALMS1 gene within the critical region on 2p13 and detected mutations in ALMS1 resulting in Alstrom syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11941370+11941369" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Hearn, T., Renforth, G. L., Spalluto, C., Hanley, N. A., Piper, K., Brickwood, S., White, C., Connolly, V., Taylor, J. F. N., Russell-Eggitt, I., Bonneau, D., Walker, M., Wilson, D. I. <strong>Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alstrom syndrome.</strong> Nature Genet. 31: 79-83, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941370</a>] [<a href="https://doi.org/10.1038/ng874" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11941370">Hearn et al. (2002)</a> detected 6 different mutations (2 nonsense and 4 frameshift causing premature stop codons) in affected members of 7 families segregating Alstrom syndrome. <a href="#4" class="mim-tip-reference" title="Collin, G. B., Marshall, J. D., Ikeda, A., So, W. V., Russell-Eggitt, I., Maffei, P., Beck, S., Boerkoel, C. F., Sicolo, N., Martin, M., Nishina, P. M., Naggert, J. K. <strong>Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome.</strong> Nature Genet. 31: 74-78, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941369</a>] [<a href="https://doi.org/10.1038/ng867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11941369">Collin et al. (2002)</a> identified 6 different mutations (4 frameshift and 2 nonsense) in affected members of 6 unrelated families with Alstrom syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11941370+11941369" 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="Collin, G. B., Marshall, J. D., Ikeda, A., So, W. V., Russell-Eggitt, I., Maffei, P., Beck, S., Boerkoel, C. F., Sicolo, N., Martin, M., Nishina, P. M., Naggert, J. K. <strong>Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome.</strong> Nature Genet. 31: 74-78, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941369</a>] [<a href="https://doi.org/10.1038/ng867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11941369">Collin et al. (2002)</a> reasoned that the infantile obesity observed in individuals with Alstrom syndrome is probably caused by mutation in ALMS1, as it constitutes a relatively early (as early as 6 months) phenotype observed in all affected children. The early onset of obesity, anecdotal reports of hyperphagia, and the sensory deficits observed in individuals with Alstrom syndrome suggested to <a href="#4" class="mim-tip-reference" title="Collin, G. B., Marshall, J. D., Ikeda, A., So, W. V., Russell-Eggitt, I., Maffei, P., Beck, S., Boerkoel, C. F., Sicolo, N., Martin, M., Nishina, P. M., Naggert, J. K. <strong>Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome.</strong> Nature Genet. 31: 74-78, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941369</a>] [<a href="https://doi.org/10.1038/ng867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11941369">Collin et al. (2002)</a> that the obesity is due to loss of ALMS1 function in the central nervous system. Nearly all individuals with Alstrom syndrome develop type 2 diabetes (<a href="/entry/125853">125853</a>), suggesting that ALMS1 may be involved in 'diabesity,' a term used by <a href="#4" class="mim-tip-reference" title="Collin, G. B., Marshall, J. D., Ikeda, A., So, W. V., Russell-Eggitt, I., Maffei, P., Beck, S., Boerkoel, C. F., Sicolo, N., Martin, M., Nishina, P. M., Naggert, J. K. <strong>Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome.</strong> Nature Genet. 31: 74-78, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941369</a>] [<a href="https://doi.org/10.1038/ng867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11941369">Collin et al. (2002)</a> for combined obesity and diabetes susceptibility due to altered function of a single gene. This distinguishes it from the common forms of obesity, in which the genes that are presumably involved appear to interact with independently segregating genes that confer diabetes susceptibility, as not all obese individuals develop type 2 diabetes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11941369" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Marshall, J. D., Hinman, E. G., Collin, G. B., Beck, S., Cerqueira, R., Maffei, P., Milan, G., Zhang, W., Wilson, D. I., Hearn, T., Tavares, P., Vettor, R., Veronese, C., Martin, M., So, W. V., Nishina, P. M., Naggert, J. K. <strong>Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alstrom syndrome.</strong> Hum. Mutat. 28: 1114-1123, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17594715/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17594715</a>] [<a href="https://doi.org/10.1002/humu.20577" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17594715">Marshall et al. (2007)</a> identified a total of 79 mutations in the ALMS1 gene, including 55 novel mutations, among 250 individuals with a clinical diagnosis of Alstrom syndrome from 206 unrelated kindreds. There were 32 mutations in exon 16, 19 mutations in exon 10, and 17 mutations in exon 8, suggesting that these regions represent mutation hotspots. The most common allele was a 1-bp deletion (10775delC; <a href="#0003">606844.0003</a>), identified in 12% of mutated alleles. Common haplotypes were observed in kindreds of English descent who carried this allele, suggesting a founder effect. A genotype-phenotype correlation analysis in a subset of 58 patients found a trend for disease-causing variants in exon 16 and a more severe phenotype. These patients tended to have onset of retinal degeneration before age 1 year (p = 0.02), urologic dysfunction (p = 0.02), dilated cardiomyopathy (p = 0.03), and diabetes (p = 0.03). A significant association was found between alterations in exon 8 and absent, mild, or delayed renal disease (p = 0.0007). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17594715" 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 2 cousins with Alstrom syndrome from a consanguineous Turkish pedigree, <a href="#13" class="mim-tip-reference" title="Taskesen, M., Collin, G. B., Evsikov, A. V., Guzel, A., Ozgul, R. K., Marshall, J. D., Naggert, J. K. <strong>Novel Alu retrotransposon insertion leading to Alstrom syndrome.</strong> Hum. Genet. 131: 407-413, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21877133/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21877133</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21877133[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/s00439-011-1083-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21877133">Taskesen et al. (2012)</a> identified homozygosity for insertion of a novel 333-bp Alu Ya5 SINE retrotransposon into exon 16 of the ALMS1 gene (<a href="#0008">606844.0008</a>). The severely affected male proband died at 14 years of age of multiple organ failure after an episode of acute gastroenteritis; his 6-year-old female cousin developed vision loss and obesity in early childhood and had hypertriglyceridemia but otherwise normal hepatic, pulmonary, cardiac, and renal function and normal hearing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21877133" 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>See <a href="#0009">606844.0009</a> for a possible association between Leber congenital amaurosis (LCA; see <a href="/entry/204000">204000</a>) and mutation in the ALMS1 gene.</p>
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<p><a href="#1" class="mim-tip-reference" title="Collin, G. B., Cyr, E., Bronson, R., Marshall, J. D., Gifford, E. J., Hicks, W., Murray, S. A., Zheng, Q. Y., Smith, R. S., Nishina, P. M., Naggert, J. K. <strong>Alms1-disrupted mice recapitulate human Alstrom syndrome.</strong> Hum. Molec. Genet. 14: 2323-2333, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16000322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16000322</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16000322[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/10.1093/hmg/ddi235" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16000322">Collin et al. (2005)</a> generated a mouse model of Alstrom syndrome using an Alms1 gene-trapped ES cell line. Alms1 -/- mice developed features similar to human patients with ALMS, including obesity, hypogonadism, hyperinsulinemia, retinal dysfunction, and late-onset hearing loss. Insulin resistance and increased body weight were apparent at 8 to 12 weeks of age, with hyperglycemia manifesting at 16 weeks of age. Alms1 -/- mice displayed abnormal auditory brainstem responses after 8 months of age. Diminished cone ERG b-wave response was observed early, followed by the degeneration of photoreceptor cells. Electron microscopy revealed accumulation of intracellular vesicles in the inner segments of photoreceptors, whereas immunohistochemical analysis showed mislocalization of rhodopsin (RHO; <a href="/entry/180380">180380</a>) to the outer nuclear layer. <a href="#1" class="mim-tip-reference" title="Collin, G. B., Cyr, E., Bronson, R., Marshall, J. D., Gifford, E. J., Hicks, W., Murray, S. A., Zheng, Q. Y., Smith, R. S., Nishina, P. M., Naggert, J. K. <strong>Alms1-disrupted mice recapitulate human Alstrom syndrome.</strong> Hum. Molec. Genet. 14: 2323-2333, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16000322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16000322</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16000322[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/10.1093/hmg/ddi235" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16000322">Collin et al. (2005)</a> suggested that ALMS1 may play a role in intracellular trafficking. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16000322" 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="#7" class="mim-tip-reference" title="Li, G., Vega, R., Nelms, K., Gekakis, N., Goodnow, C., McNamara, P., Wu, H., Hong, N. A., Glynne, R. <strong>A role for Alstrom syndrome protein, Alms1, in kidney ciliogenesis and cellular quiescence.</strong> PLoS Genet. 3: e8, 2007. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17206865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17206865</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17206865[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1371/journal.pgen.0030008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17206865">Li et al. (2007)</a> studied a mouse model of Alstrom syndrome in which the Alms1 protein was prematurely terminated at 2,130 amino acids. Primary fibroblasts and kidney cells from homozygous mutant mice expressed both mutant mRNA and protein, and they showed normal primary cilia and normal localization of the mutant protein. Homozygous mutant mice increased in weight faster than wildtype mice due to increased fat mass, and they had abnormal blood lipid chemistry, defective sperm formation, and defective rhodopsin transport in the retina. By 6 months of age, homozygous mutant mice developed multiple dilated cortical tubules, and older animals showed loss of cilia from kidney proximal tubules, which was associated with foci of apoptosis or proliferation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17206865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=606844[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2104104085 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2104104085;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=rs2104104085" 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=rs2104104085" 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=RCV000004175" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004175" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004175</a>
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<p>In the large consanguineous Acadian kindred with Alstrom syndrome (ALMS; <a href="/entry/203800">203800</a>) studied by <a href="#3" class="mim-tip-reference" title="Collin, G. B., Marshall, J. D., Cardon, L. R., Nishina, P. M. <strong>Homozygosity mapping of Alstrom syndrome to chromosome 2p.</strong> Hum. Molec. Genet. 6: 213-219, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9063741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9063741</a>] [<a href="https://doi.org/10.1093/hmg/6.2.213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9063741">Collin et al. (1997)</a> and <a href="#10" class="mim-tip-reference" title="Marshall, J. D., Ludman, M. D., Shea, S. E., Salisbury, S. R., Willi, S. M., LaRoche, R. G., Nishina, P. M. <strong>Genealogy, natural history, and phenotype of Alstrom syndrome in a large Acadian kindred and three additional families.</strong> Am. J. Med. Genet. 73: 150-161, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9409865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9409865</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19971212)73:2<150::aid-ajmg9>3.0.co;2-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9409865">Marshall et al. (1997)</a>, <a href="#4" class="mim-tip-reference" title="Collin, G. B., Marshall, J. D., Ikeda, A., So, W. V., Russell-Eggitt, I., Maffei, P., Beck, S., Boerkoel, C. F., Sicolo, N., Martin, M., Nishina, P. M., Naggert, J. K. <strong>Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome.</strong> Nature Genet. 31: 74-78, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941369</a>] [<a href="https://doi.org/10.1038/ng867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11941369">Collin et al. (2002)</a> identified an insertion of 19 bp in exon 16 of the ALMS1 gene, causing a frameshift resulting in early termination at codon 3530. All 5 affected subjects from the extended pedigree were homozygous with respect to the insertion. Transmission of the insertion allele in unaffected carriers was consistent with previously reported haplotypes (<a href="#3" class="mim-tip-reference" title="Collin, G. B., Marshall, J. D., Cardon, L. R., Nishina, P. M. <strong>Homozygosity mapping of Alstrom syndrome to chromosome 2p.</strong> Hum. Molec. Genet. 6: 213-219, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9063741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9063741</a>] [<a href="https://doi.org/10.1093/hmg/6.2.213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9063741">Collin et al., 1997</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9409865+9063741+11941369" 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">rs193919338 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193919338;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=rs193919338" 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=rs193919338" 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=RCV000004176" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004176" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004176</a>
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<p>In a consanguineous Italian family with Alstrom syndrome (ALMS; <a href="/entry/203800">203800</a>), <a href="#4" class="mim-tip-reference" title="Collin, G. B., Marshall, J. D., Ikeda, A., So, W. V., Russell-Eggitt, I., Maffei, P., Beck, S., Boerkoel, C. F., Sicolo, N., Martin, M., Nishina, P. M., Naggert, J. K. <strong>Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome.</strong> Nature Genet. 31: 74-78, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941369</a>] [<a href="https://doi.org/10.1038/ng867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11941369">Collin et al. (2002)</a> observed an 8383C-T transition in the ALMS1 gene in homozygous state, causing a nonsense change, glu2795 to ter (G2795X). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11941369" 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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ALMS1, 1-BP DEL, 10775C
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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> rs387906312 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906312;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/rs387906312?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=rs387906312" 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=rs387906312" 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=RCV000004177 OR RCV000726756 OR RCV001075440 OR RCV004018550" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004177, RCV000726756, RCV001075440, RCV004018550" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004177...</a>
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<p>In 2 unrelated young adults with Alstrom syndrome (ALMS; <a href="/entry/203800">203800</a>), <a href="#4" class="mim-tip-reference" title="Collin, G. B., Marshall, J. D., Ikeda, A., So, W. V., Russell-Eggitt, I., Maffei, P., Beck, S., Boerkoel, C. F., Sicolo, N., Martin, M., Nishina, P. M., Naggert, J. K. <strong>Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome.</strong> Nature Genet. 31: 74-78, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941369</a>] [<a href="https://doi.org/10.1038/ng867" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11941369">Collin et al. (2002)</a> found a 10775delC mutation in the ALMS1 gene. One subject was a 19-year-old male of British ancestry and the other a 21-year-old male who traced his ancestry to Britain 2 centuries earlier. Both presented with infantile cardiomyopathy within the first 2 months of life and subsequently developed short stature, scoliosis, type 2 diabetes, and renal insufficiency. However, they differed in the course of their disease presentation. The first experienced a sudden recurrence of dilated cardiomyopathy at age 18 and had no evidence of hepatic dysfunction, whereas the second presented with severe hepatic failure at age 20 and had not had a recurrence of cardiomyopathy. This difference in disease progression in individuals carrying the same mutation suggested that the phenotypic variability observed in many individuals with Alstrom syndrome may be the result of genetic or environmental modifiers interacting with the ALMS1 locus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11941369" 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 2 sibs with Alstrom syndrome, <a href="#5" class="mim-tip-reference" title="Hearn, T., Renforth, G. L., Spalluto, C., Hanley, N. A., Piper, K., Brickwood, S., White, C., Connolly, V., Taylor, J. F. N., Russell-Eggitt, I., Bonneau, D., Walker, M., Wilson, D. I. <strong>Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alstrom syndrome.</strong> Nature Genet. 31: 79-83, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941370</a>] [<a href="https://doi.org/10.1038/ng874" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11941370">Hearn et al. (2002)</a> found compound heterozygosity for the 10775delC mutation and a trp3664-to-ter mutation in the ALMS1 gene (W3664X; <a href="#0006">606844.0006</a>); the former was inherited from the father and the latter presumably from the mother. The W3664X mutation was caused by a G-to-A transition at nucleotide 10992. <a href="#5" class="mim-tip-reference" title="Hearn, T., Renforth, G. L., Spalluto, C., Hanley, N. A., Piper, K., Brickwood, S., White, C., Connolly, V., Taylor, J. F. N., Russell-Eggitt, I., Bonneau, D., Walker, M., Wilson, D. I. <strong>Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alstrom syndrome.</strong> Nature Genet. 31: 79-83, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941370</a>] [<a href="https://doi.org/10.1038/ng874" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11941370">Hearn et al. (2002)</a> found the 10775delC mutation in 3 additional families not known to be related to the original family in which this mutation was identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11941370" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Marshall, J. D., Hinman, E. G., Collin, G. B., Beck, S., Cerqueira, R., Maffei, P., Milan, G., Zhang, W., Wilson, D. I., Hearn, T., Tavares, P., Vettor, R., Veronese, C., Martin, M., So, W. V., Nishina, P. M., Naggert, J. K. <strong>Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alstrom syndrome.</strong> Hum. Mutat. 28: 1114-1123, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17594715/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17594715</a>] [<a href="https://doi.org/10.1002/humu.20577" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17594715">Marshall et al. (2007)</a> identified the 10775delC mutation in 12% of mutated alleles from a large study of 250 patients with ALMS. Common haplotypes were observed in kindreds of English descent who carried this allele, suggesting a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17594715" 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">rs387906313 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906313;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=rs387906313" 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=rs387906313" 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=RCV000004178 OR RCV000599323" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004178, RCV000599323" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004178...</a>
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<p><a href="#5" class="mim-tip-reference" title="Hearn, T., Renforth, G. L., Spalluto, C., Hanley, N. A., Piper, K., Brickwood, S., White, C., Connolly, V., Taylor, J. F. N., Russell-Eggitt, I., Bonneau, D., Walker, M., Wilson, D. I. <strong>Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alstrom syndrome.</strong> Nature Genet. 31: 79-83, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941370</a>] [<a href="https://doi.org/10.1038/ng874" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11941370">Hearn et al. (2002)</a> described a patient with Alstrom syndrome (ALMS; <a href="/entry/203800">203800</a>) who was compound heterozygous for mutations involving the ALMS1 gene. The ALMS1 gene on the maternal chromosome 2 was disrupted by the translocation break; the ALMS1 gene on the paternal chromosome carried a deletion of 2 bp in exon 8 (2141delCT) that was predicted to cause premature termination 5 codons downstream of the deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11941370" 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">rs193919339 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193919339;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=rs193919339" 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=rs193919339" 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=RCV000004180" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004180" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004180</a>
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<p>For discussion of the trp3664-to-ter (W3664X) mutation in the ALMS1 gene that was found in compound heterozygous state in patients with Alstrom syndrome (ALMS; <a href="/entry/203800">203800</a>) by <a href="#5" class="mim-tip-reference" title="Hearn, T., Renforth, G. L., Spalluto, C., Hanley, N. A., Piper, K., Brickwood, S., White, C., Connolly, V., Taylor, J. F. N., Russell-Eggitt, I., Bonneau, D., Walker, M., Wilson, D. I. <strong>Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alstrom syndrome.</strong> Nature Genet. 31: 79-83, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941370</a>] [<a href="https://doi.org/10.1038/ng874" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11941370">Hearn et al. (2002)</a>, see <a href="#0003">606844.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11941370" 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> rs193919340 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193919340;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/rs193919340?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=rs193919340" 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=rs193919340" 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=RCV000004181 OR RCV003313026" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004181, RCV003313026" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004181...</a>
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<p>In 3 Turkish sisters with Alstrom syndrome (ALMS; <a href="/entry/203800">203800</a>), <a href="#12" class="mim-tip-reference" title="Ozgul, R. K., Satman, I., Collin, G. B., Hinman, E. G., Marshall, J. D., Kocaman, O., Tutuncu, Y., Yilmaz, T., Naggert, J. K. <strong>Molecular analysis and long-term clinical evaluation of three siblings with Alstrom syndrome.</strong> Clin. Genet. 72: 351-356, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17850632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17850632</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00848.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17850632">Ozgul et al. (2007)</a> identified a homozygous 8164C-T transition in the ALMS1 gene, resulting in an arg2722-to-ter (R2722X) substitution. The girls had been followed for 20 years and showed typical clinical features of the disorder with some additional unusual findings such as pes planus, tooth enamel discoloration, and structural renal anomalies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17850632" 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 ALSTROM SYNDROME</strong>
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ALMS1, 333-BP ALU INS, EX16
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000030808" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030808" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030808</a>
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<p>In 2 cousins with Alstrom syndrome (ALMS; <a href="/entry/203800">203800</a>) from a consanguineous Turkish pedigree, <a href="#13" class="mim-tip-reference" title="Taskesen, M., Collin, G. B., Evsikov, A. V., Guzel, A., Ozgul, R. K., Marshall, J. D., Naggert, J. K. <strong>Novel Alu retrotransposon insertion leading to Alstrom syndrome.</strong> Hum. Genet. 131: 407-413, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21877133/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21877133</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21877133[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/s00439-011-1083-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21877133">Taskesen et al. (2012)</a> identified homozygosity for insertion of a 333-bp Alu Ya5 element in exon 16 of the ALMS1 gene, predicted to cause a frameshift resulting in a premature termination codon. PCR genotyping for the presence of the Alu allele revealed that the wildtype allele produces a 313-bp PCR product, whereas the Alu allele produces a 646-bp PCR product. <a href="#13" class="mim-tip-reference" title="Taskesen, M., Collin, G. B., Evsikov, A. V., Guzel, A., Ozgul, R. K., Marshall, J. D., Naggert, J. K. <strong>Novel Alu retrotransposon insertion leading to Alstrom syndrome.</strong> Hum. Genet. 131: 407-413, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21877133/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21877133</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21877133[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/s00439-011-1083-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21877133">Taskesen et al. (2012)</a> did not detect a 100% identical sequence anywhere in the human genome assembly, indicating a previously unknown polymorphism of active Alu Ya5 elements. The authors suggested that the truncation of 34 nucleotides at the 5-prime end of the ALMS1(Alu) allele, possibly due to incomplete reverse transcription during transposition, made it likely that this particular element would no longer be transcription- or retroposition-competent. The ALMS1(Alu) allele was detected in 2 (6.9%) of 29 unaffected individuals from the same Turkish village as the affected pedigree, but was not found in 50 unrelated Turkish controls. The severely affected male proband died at 14 years of age of multiple organ failure after an episode of acute gastroenteritis; his 6-year-old female cousin developed vision loss and obesity in early childhood and had hypertriglyceridemia but otherwise normal hepatic, pulmonary, cardiac, and renal function and normal hearing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21877133" 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">rs397514576 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514576;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=rs397514576" 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=rs397514576" 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=RCV000032964" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032964" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032964</a>
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<p>In a study of 250 patients with Alstrom syndrome (ALMS; <a href="/entry/203800">203800</a>), <a href="#9" class="mim-tip-reference" title="Marshall, J. D., Hinman, E. G., Collin, G. B., Beck, S., Cerqueira, R., Maffei, P., Milan, G., Zhang, W., Wilson, D. I., Hearn, T., Tavares, P., Vettor, R., Veronese, C., Martin, M., So, W. V., Nishina, P. M., Naggert, J. K. <strong>Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alstrom syndrome.</strong> Hum. Mutat. 28: 1114-1123, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17594715/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17594715</a>] [<a href="https://doi.org/10.1002/humu.20577" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17594715">Marshall et al. (2007)</a> identified 2 alleles carrying a 10945G-T transversion in exon 16 of the ALMS1 gene, resulting in a glu3649-to-ter (E3649X) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17594715" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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In members of a large consanguineous Saudi Arabian family who had been diagnosed with Leber congenital amaurosis (LCA; see <a href="/entry/204000">204000</a>), <a href="#14" class="mim-tip-reference" title="Wang, X., Wang, H., Cao, M., Li, Z., Chen, X., Patenia, C., Gore, A., Abboud, E. B., Al-Rajhi, A. A., Lewis, R. A., Lupski, J. R., Mardon, G., Zhang, K., Muzny, D., Gibbs, R. A., Chen, R. <strong>Whole-exome sequencing identifies ALMS1, IQCB1, CNGA3, and MYO7A mutations in patients with Leber congenital amaurosis.</strong> Hum. Mutat. 32: 1450-1459, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21901789/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21901789</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21901789[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/10.1002/humu.21587" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21901789">Wang et al. (2011)</a> identified homozygosity for the E3649X mutation in the ALMS1 gene. The authors stated that no other syndromic features such as hearing loss or obesity had been reported in the Saudi Arabian patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21901789" 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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Collin, G. B., Cyr, E., Bronson, R., Marshall, J. D., Gifford, E. J., Hicks, W., Murray, S. A., Zheng, Q. Y., Smith, R. S., Nishina, P. M., Naggert, J. K.
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<strong>Alms1-disrupted mice recapitulate human Alstrom syndrome.</strong>
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Hum. Molec. Genet. 14: 2323-2333, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16000322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16000322</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16000322[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=16000322" 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/10.1093/hmg/ddi235" target="_blank">Full Text</a>]
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Collin, G. B., Marshall, J. D., Boerkoel, C. F., Levin, A. V., Weksberg, R., Greenberg, J., Michaud, J. L., Naggert, J. K., Nishina, P. M.
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<strong>Alstrom syndrome: further evidence for linkage to human chromosome 2p13.</strong>
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Hum. Genet. 105: 474-479, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10598815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10598815</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10598815" 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/s004390051133" target="_blank">Full Text</a>]
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<a id="Collin1997" class="mim-anchor"></a>
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Collin, G. B., Marshall, J. D., Cardon, L. R., Nishina, P. M.
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<strong>Homozygosity mapping of Alstrom syndrome to chromosome 2p.</strong>
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Hum. Molec. Genet. 6: 213-219, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9063741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9063741</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9063741" 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/10.1093/hmg/6.2.213" target="_blank">Full Text</a>]
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<a id="Collin2002" class="mim-anchor"></a>
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Collin, G. B., Marshall, J. D., Ikeda, A., So, W. V., Russell-Eggitt, I., Maffei, P., Beck, S., Boerkoel, C. F., Sicolo, N., Martin, M., Nishina, P. M., Naggert, J. K.
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<strong>Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome.</strong>
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Nature Genet. 31: 74-78, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941369</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11941369" 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/ng867" target="_blank">Full Text</a>]
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<a id="Hearn2002" class="mim-anchor"></a>
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<div class="">
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Hearn, T., Renforth, G. L., Spalluto, C., Hanley, N. A., Piper, K., Brickwood, S., White, C., Connolly, V., Taylor, J. F. N., Russell-Eggitt, I., Bonneau, D., Walker, M., Wilson, D. I.
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<strong>Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alstrom syndrome.</strong>
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Nature Genet. 31: 79-83, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11941370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11941370</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11941370" 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/ng874" target="_blank">Full Text</a>]
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<a id="6" class="mim-anchor"></a>
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<a id="Knorz2010" class="mim-anchor"></a>
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<div class="">
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Knorz, V. J., Spalluto, C., Lessard, M., Purvis, T. L., Adigun, F. F., Collin, G. B., Hanley, N. A., Wilson, D. I., Hearn, T.
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<strong>Centriolar association of ALMS1 and likely centrosomal functions of the ALMS motif-containing proteins C10orf90 and KIAA1731.</strong>
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Molec. Biol. Cell 21: 3617-3629, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20844083/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20844083</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20844083" 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/10.1091/mbc.E10-03-0246" target="_blank">Full Text</a>]
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<a id="Li2007" class="mim-anchor"></a>
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Li, G., Vega, R., Nelms, K., Gekakis, N., Goodnow, C., McNamara, P., Wu, H., Hong, N. A., Glynne, R.
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<strong>A role for Alstrom syndrome protein, Alms1, in kidney ciliogenesis and cellular quiescence.</strong>
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PLoS Genet. 3: e8, 2007. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17206865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17206865</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17206865[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=17206865" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1371/journal.pgen.0030008" target="_blank">Full Text</a>]
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<a id="Macari1998" class="mim-anchor"></a>
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Macari, F., Lautier, C., Girardet, A., Dadoun, F., Darmon, P., Dutour, A., Renard, E., Bouvagnet, P., Claustres, M., Oliver, C., Grigorescu, F.
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<strong>Refinement of genetic localization of the Alstrom syndrome on chromosome 2p12-13 by linkage analysis in a North African family.</strong>
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Hum. Genet. 103: 658-661, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9921899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9921899</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9921899" 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/s004390050887" target="_blank">Full Text</a>]
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<a id="Marshall2007" class="mim-anchor"></a>
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Marshall, J. D., Hinman, E. G., Collin, G. B., Beck, S., Cerqueira, R., Maffei, P., Milan, G., Zhang, W., Wilson, D. I., Hearn, T., Tavares, P., Vettor, R., Veronese, C., Martin, M., So, W. V., Nishina, P. M., Naggert, J. K.
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<strong>Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alstrom syndrome.</strong>
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Hum. Mutat. 28: 1114-1123, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17594715/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17594715</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17594715" 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.20577" target="_blank">Full Text</a>]
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<a id="Marshall1997" class="mim-anchor"></a>
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Marshall, J. D., Ludman, M. D., Shea, S. E., Salisbury, S. R., Willi, S. M., LaRoche, R. G., Nishina, P. M.
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<strong>Genealogy, natural history, and phenotype of Alstrom syndrome in a large Acadian kindred and three additional families.</strong>
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Am. J. Med. Genet. 73: 150-161, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9409865/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9409865</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9409865" 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/(sici)1096-8628(19971212)73:2<150::aid-ajmg9>3.0.co;2-y" target="_blank">Full Text</a>]
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<a id="Nagase1997" class="mim-anchor"></a>
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Nagase, T., Ishikawa, K., Nakajima, D., Ohira, M., Seki, N., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O.
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<strong>Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.</strong>
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DNA Res. 4: 141-150, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9205841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9205841</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9205841" 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/10.1093/dnares/4.2.141" target="_blank">Full Text</a>]
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Ozgul, R. K., Satman, I., Collin, G. B., Hinman, E. G., Marshall, J. D., Kocaman, O., Tutuncu, Y., Yilmaz, T., Naggert, J. K.
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<strong>Molecular analysis and long-term clinical evaluation of three siblings with Alstrom syndrome.</strong>
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Clin. Genet. 72: 351-356, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17850632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17850632</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17850632" 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.1399-0004.2007.00848.x" target="_blank">Full Text</a>]
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<a id="Taskesen2012" class="mim-anchor"></a>
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Taskesen, M., Collin, G. B., Evsikov, A. V., Guzel, A., Ozgul, R. K., Marshall, J. D., Naggert, J. K.
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<strong>Novel Alu retrotransposon insertion leading to Alstrom syndrome.</strong>
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Hum. Genet. 131: 407-413, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21877133/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21877133</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21877133[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=21877133" 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/s00439-011-1083-9" target="_blank">Full Text</a>]
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<a id="Wang2011" class="mim-anchor"></a>
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Wang, X., Wang, H., Cao, M., Li, Z., Chen, X., Patenia, C., Gore, A., Abboud, E. B., Al-Rajhi, A. A., Lewis, R. A., Lupski, J. R., Mardon, G., Zhang, K., Muzny, D., Gibbs, R. A., Chen, R.
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<strong>Whole-exome sequencing identifies ALMS1, IQCB1, CNGA3, and MYO7A mutations in patients with Leber congenital amaurosis.</strong>
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Hum. Mutat. 32: 1450-1459, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21901789/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21901789</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21901789[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=21901789" 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.21587" target="_blank">Full Text</a>]
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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Patricia A. Hartz - updated : 10/18/2017
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Marla J. F. O'Neill - updated : 11/2/2012<br>Marla J. F. O'Neill - updated : 10/1/2012<br>George E. Tiller - updated : 1/9/2009<br>Cassandra L. Kniffin - updated : 1/8/2008<br>Cassandra L. Kniffin - updated : 11/14/2007<br>Patricia A. Hartz - updated : 8/8/2007
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Victor A. McKusick : 4/10/2002
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carol : 11/01/2019
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carol : 10/31/2019<br>alopez : 10/18/2017<br>carol : 08/17/2015<br>mcolton : 6/11/2015<br>carol : 11/2/2012<br>carol : 10/2/2012<br>terry : 10/1/2012<br>wwang : 1/9/2009<br>wwang : 1/28/2008<br>ckniffin : 1/8/2008<br>wwang : 12/14/2007<br>ckniffin : 11/14/2007<br>mgross : 8/13/2007<br>terry : 8/8/2007<br>terry : 3/24/2004<br>alopez : 6/7/2002<br>alopez : 4/10/2002<br>alopez : 4/10/2002
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<h3>
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<span class="mim-font">
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<strong>*</strong> 606844
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</h3>
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<h3>
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<span class="mim-font">
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ALMS1 CENTROSOME AND BASAL BODY ASSOCIATED PROTEIN; ALMS1
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</h3>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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<div>
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<h4>
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<span class="mim-font">
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KIAA0328
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</h4>
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<br />
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: ALMS1</em></strong>
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</span>
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</p>
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</div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 63702009;
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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: 2p13.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 2:73,385,758-73,609,919 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</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>
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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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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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2p13.1
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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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Alstrom syndrome
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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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203800
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</table>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>ALMS1 localizes to the centrosome and appears to have a role in centriole structure and function (Knorz et al., 2010). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>By sequencing clones obtained from a size-fractionated brain cDNA library, Nagase et al. (1997) cloned ALMS1, which they designated KIAA0328. The transcript contains a repetitive sequence at its 3-prime UTR. RT-PCR detected low expression in testis and little to no expression in all other tissues examined. </p><p>By linkage mapping and scrutiny of positional candidate genes, Collin et al. (2002) identified an uncharacterized transcript, KIAA0328, in which sequence variations were found to segregate with Alstrom syndrome (ALMS; 203800). By aligning KIAA0328 with overlapping transcripts from several sequence databases, they obtained a full-length cDNA sequence of 12,871 basepairs with an open reading frame of 4,169 amino acids. </p><p>Hearn et al. (2002) studied a unique patient with a familial balanced reciprocal translocation involving 2p13 in which the KIAA0328 gene was disrupted by the translocation and the other copy disrupted by an intragenic mutation to cause Alstrom syndrome. By RT-PCR with exon prediction and specific primer design, they identified an ALMS1 sequence containing an open reading frame of 12.5 kb that encodes a protein of 4,169 amino acids. The protein contains a large tandem-repeat domain comprising 34 imperfect repetitions of 47 amino acids. Hearn et al. (2002) stated that their identification of the ALMS1 gene using cloning of the breakpoint of a balanced translocation represented the first use of this strategy to identify a gene involved in a recessive disorder. </p><p>Using real-time PCR of mouse tissues, Li et al. (2007) detected highest Alms1 expression in testis. Expression was moderate in brain, eye, lung, and olfactory bulb and low in spleen, liver, and kidney. Immunohistochemical analysis localized Alms1 to the base of cilia in cultured mouse kidney cells. </p><p>Knorz et al. (2010) reported that the deduced 4,169-amino acid ALMS1 protein has an N-terminal stretch of 17 consecutive glu residues, followed by a tandem repeat domain, a putative leucine zipper, his-rich and ser-rich regions, and a C-terminal ALMS motif domain. Unlike many other centrosomal proteins, ALMS1 has limited potential to form coiled-coils. Knorz et al. (2010) also described a splice variant of ALMS1 that includes exon 2, which introduces 42 additional residues. This variant is rarely expressed in humans. High-resolution immunofluorescence microscopy of hTERT-RPE1 cells detected ALMS1 at the proximal ends of centrioles and basal bodies. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Li et al. (2007) found that depletion of Alms1 by short interfering RNA in mouse inner medullary collecting duct cells caused defective ciliogenesis. Alms1 knockdown did not affect transcription of ciliary genes, but cilia were stunted and mutant cells lacked the ability to increase calcium influx in response to mechanical stimuli. The stunted cilium phenotype was rescued by transfection of a cDNA encoding the N-terminal 1,282 amino acids of Alms1. </p><p>Using RNA interference, Knorz et al. (2010) found that knockdown of ALMS1 in human cells reduced the intensity of CNAP1 (CEP2; 609689) staining at the centrosome, increased the distance between centrioles, and caused a defect in trafficking of centriolar satellite PCM1 (600299)-positive granules. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene 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>Collin et al. (2002) and Hearn et al. (2002) identified 23 exons in the ALMS1 gene. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By radiation hybrid analysis, Nagase et al. (1997) mapped the ALMS1 gene to chromosome 2. </p><p>As a result of a linkage study in a large French Acadian kindred with Alstrom syndrome and because of evidence of founder effect, Collin et al. (1997) were able to use homozygosity mapping to identify the Alstrom disease locus. In a genomewide screen, haplotype sharing for a region on chromosome 2 was observed in all affected individuals. Two-point linkage analysis resulted in a maximum lod score of 3.84 at theta = 0.00 for marker D2S292. By testing additional markers, the disease gene was localized to a 14.9-cM region on 2p14-p13 (see Figure 3 of Collin et al., 1997). In a North African family in Algeria, Macari et al. (1998) refined the localization of the Alstrom syndrome locus to 2p13-p12, reducing the genetic interval to 6.1 cM. Collin et al. (1999) confirmed the mapping to 2p13 by performing a linkage study in 12 additional families. A maximum 2-point lod score of 7.13 (theta = 0.00) for marker D2S2110 and a maximum cumulative multipoint lod score of 9.16 for marker D2S2110 were observed. Meiotic recombination events localized the critical region containing the ALMS1 locus to a 6.1-cM interval flanked by markers D2S327 and D2S286. </p><p>Collin et al. (2002) and Hearn et al. (2002) cloned the ALMS1 gene within the critical region on 2p13 and detected mutations in ALMS1 resulting in Alstrom syndrome. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Hearn et al. (2002) detected 6 different mutations (2 nonsense and 4 frameshift causing premature stop codons) in affected members of 7 families segregating Alstrom syndrome. Collin et al. (2002) identified 6 different mutations (4 frameshift and 2 nonsense) in affected members of 6 unrelated families with Alstrom syndrome. </p><p>Collin et al. (2002) reasoned that the infantile obesity observed in individuals with Alstrom syndrome is probably caused by mutation in ALMS1, as it constitutes a relatively early (as early as 6 months) phenotype observed in all affected children. The early onset of obesity, anecdotal reports of hyperphagia, and the sensory deficits observed in individuals with Alstrom syndrome suggested to Collin et al. (2002) that the obesity is due to loss of ALMS1 function in the central nervous system. Nearly all individuals with Alstrom syndrome develop type 2 diabetes (125853), suggesting that ALMS1 may be involved in 'diabesity,' a term used by Collin et al. (2002) for combined obesity and diabetes susceptibility due to altered function of a single gene. This distinguishes it from the common forms of obesity, in which the genes that are presumably involved appear to interact with independently segregating genes that confer diabetes susceptibility, as not all obese individuals develop type 2 diabetes. </p><p>Marshall et al. (2007) identified a total of 79 mutations in the ALMS1 gene, including 55 novel mutations, among 250 individuals with a clinical diagnosis of Alstrom syndrome from 206 unrelated kindreds. There were 32 mutations in exon 16, 19 mutations in exon 10, and 17 mutations in exon 8, suggesting that these regions represent mutation hotspots. The most common allele was a 1-bp deletion (10775delC; 606844.0003), identified in 12% of mutated alleles. Common haplotypes were observed in kindreds of English descent who carried this allele, suggesting a founder effect. A genotype-phenotype correlation analysis in a subset of 58 patients found a trend for disease-causing variants in exon 16 and a more severe phenotype. These patients tended to have onset of retinal degeneration before age 1 year (p = 0.02), urologic dysfunction (p = 0.02), dilated cardiomyopathy (p = 0.03), and diabetes (p = 0.03). A significant association was found between alterations in exon 8 and absent, mild, or delayed renal disease (p = 0.0007). </p><p>In 2 cousins with Alstrom syndrome from a consanguineous Turkish pedigree, Taskesen et al. (2012) identified homozygosity for insertion of a novel 333-bp Alu Ya5 SINE retrotransposon into exon 16 of the ALMS1 gene (606844.0008). The severely affected male proband died at 14 years of age of multiple organ failure after an episode of acute gastroenteritis; his 6-year-old female cousin developed vision loss and obesity in early childhood and had hypertriglyceridemia but otherwise normal hepatic, pulmonary, cardiac, and renal function and normal hearing. </p><p>See 606844.0009 for a possible association between Leber congenital amaurosis (LCA; see 204000) and mutation in the ALMS1 gene.</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Collin et al. (2005) generated a mouse model of Alstrom syndrome using an Alms1 gene-trapped ES cell line. Alms1 -/- mice developed features similar to human patients with ALMS, including obesity, hypogonadism, hyperinsulinemia, retinal dysfunction, and late-onset hearing loss. Insulin resistance and increased body weight were apparent at 8 to 12 weeks of age, with hyperglycemia manifesting at 16 weeks of age. Alms1 -/- mice displayed abnormal auditory brainstem responses after 8 months of age. Diminished cone ERG b-wave response was observed early, followed by the degeneration of photoreceptor cells. Electron microscopy revealed accumulation of intracellular vesicles in the inner segments of photoreceptors, whereas immunohistochemical analysis showed mislocalization of rhodopsin (RHO; 180380) to the outer nuclear layer. Collin et al. (2005) suggested that ALMS1 may play a role in intracellular trafficking. </p><p>Li et al. (2007) studied a mouse model of Alstrom syndrome in which the Alms1 protein was prematurely terminated at 2,130 amino acids. Primary fibroblasts and kidney cells from homozygous mutant mice expressed both mutant mRNA and protein, and they showed normal primary cilia and normal localization of the mutant protein. Homozygous mutant mice increased in weight faster than wildtype mice due to increased fat mass, and they had abnormal blood lipid chemistry, defective sperm formation, and defective rhodopsin transport in the retina. By 6 months of age, homozygous mutant mice developed multiple dilated cortical tubules, and older animals showed loss of cilia from kidney proximal tubules, which was associated with foci of apoptosis or proliferation. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>9 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 ALSTROM SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ALMS1, 19-BP INS, EX16
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<br />
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SNP: rs2104104085,
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ClinVar: RCV000004175
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In the large consanguineous Acadian kindred with Alstrom syndrome (ALMS; 203800) studied by Collin et al. (1997) and Marshall et al. (1997), Collin et al. (2002) identified an insertion of 19 bp in exon 16 of the ALMS1 gene, causing a frameshift resulting in early termination at codon 3530. All 5 affected subjects from the extended pedigree were homozygous with respect to the insertion. Transmission of the insertion allele in unaffected carriers was consistent with previously reported haplotypes (Collin et al., 1997). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 ALSTROM SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ALMS1, GLU2795TER
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<br />
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SNP: rs193919338,
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ClinVar: RCV000004176
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a consanguineous Italian family with Alstrom syndrome (ALMS; 203800), Collin et al. (2002) observed an 8383C-T transition in the ALMS1 gene in homozygous state, causing a nonsense change, glu2795 to ter (G2795X). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 ALSTROM SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ALMS1, 1-BP DEL, 10775C
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<br />
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SNP: rs387906312,
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gnomAD: rs387906312,
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ClinVar: RCV000004177, RCV000726756, RCV001075440, RCV004018550
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 unrelated young adults with Alstrom syndrome (ALMS; 203800), Collin et al. (2002) found a 10775delC mutation in the ALMS1 gene. One subject was a 19-year-old male of British ancestry and the other a 21-year-old male who traced his ancestry to Britain 2 centuries earlier. Both presented with infantile cardiomyopathy within the first 2 months of life and subsequently developed short stature, scoliosis, type 2 diabetes, and renal insufficiency. However, they differed in the course of their disease presentation. The first experienced a sudden recurrence of dilated cardiomyopathy at age 18 and had no evidence of hepatic dysfunction, whereas the second presented with severe hepatic failure at age 20 and had not had a recurrence of cardiomyopathy. This difference in disease progression in individuals carrying the same mutation suggested that the phenotypic variability observed in many individuals with Alstrom syndrome may be the result of genetic or environmental modifiers interacting with the ALMS1 locus. </p><p>In 2 sibs with Alstrom syndrome, Hearn et al. (2002) found compound heterozygosity for the 10775delC mutation and a trp3664-to-ter mutation in the ALMS1 gene (W3664X; 606844.0006); the former was inherited from the father and the latter presumably from the mother. The W3664X mutation was caused by a G-to-A transition at nucleotide 10992. Hearn et al. (2002) found the 10775delC mutation in 3 additional families not known to be related to the original family in which this mutation was identified. </p><p>Marshall et al. (2007) identified the 10775delC mutation in 12% of mutated alleles from a large study of 250 patients with ALMS. Common haplotypes were observed in kindreds of English descent who carried this allele, suggesting a founder effect. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 ALSTROM SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ALMS1, 2-BP DEL, 2141CT
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<br />
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SNP: rs387906313,
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ClinVar: RCV000004178, RCV000599323
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Hearn et al. (2002) described a patient with Alstrom syndrome (ALMS; 203800) who was compound heterozygous for mutations involving the ALMS1 gene. The ALMS1 gene on the maternal chromosome 2 was disrupted by the translocation break; the ALMS1 gene on the paternal chromosome carried a deletion of 2 bp in exon 8 (2141delCT) that was predicted to cause premature termination 5 codons downstream of the deletion. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-text-font">
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<strong>.0005 MOVED TO 606844.0003</strong>
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</span>
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</h4>
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</div>
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<div>
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<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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<h4>
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<span class="mim-font">
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<strong>.0006 ALSTROM SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ALMS1, TRP3664TER
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<br />
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SNP: rs193919339,
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ClinVar: RCV000004180
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the trp3664-to-ter (W3664X) mutation in the ALMS1 gene that was found in compound heterozygous state in patients with Alstrom syndrome (ALMS; 203800) by Hearn et al. (2002), see 606844.0003. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0007 ALSTROM SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ALMS1, ARG2722TER
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<br />
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SNP: rs193919340,
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gnomAD: rs193919340,
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ClinVar: RCV000004181, RCV003313026
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 3 Turkish sisters with Alstrom syndrome (ALMS; 203800), Ozgul et al. (2007) identified a homozygous 8164C-T transition in the ALMS1 gene, resulting in an arg2722-to-ter (R2722X) substitution. The girls had been followed for 20 years and showed typical clinical features of the disorder with some additional unusual findings such as pes planus, tooth enamel discoloration, and structural renal anomalies. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0008 ALSTROM SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ALMS1, 333-BP ALU INS, EX16
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<br />
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ClinVar: RCV000030808
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 cousins with Alstrom syndrome (ALMS; 203800) from a consanguineous Turkish pedigree, Taskesen et al. (2012) identified homozygosity for insertion of a 333-bp Alu Ya5 element in exon 16 of the ALMS1 gene, predicted to cause a frameshift resulting in a premature termination codon. PCR genotyping for the presence of the Alu allele revealed that the wildtype allele produces a 313-bp PCR product, whereas the Alu allele produces a 646-bp PCR product. Taskesen et al. (2012) did not detect a 100% identical sequence anywhere in the human genome assembly, indicating a previously unknown polymorphism of active Alu Ya5 elements. The authors suggested that the truncation of 34 nucleotides at the 5-prime end of the ALMS1(Alu) allele, possibly due to incomplete reverse transcription during transposition, made it likely that this particular element would no longer be transcription- or retroposition-competent. The ALMS1(Alu) allele was detected in 2 (6.9%) of 29 unaffected individuals from the same Turkish village as the affected pedigree, but was not found in 50 unrelated Turkish controls. The severely affected male proband died at 14 years of age of multiple organ failure after an episode of acute gastroenteritis; his 6-year-old female cousin developed vision loss and obesity in early childhood and had hypertriglyceridemia but otherwise normal hepatic, pulmonary, cardiac, and renal function and normal hearing. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0009 ALSTROM SYNDROME</strong>
|
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</span>
|
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ALMS1, GLU3649TER
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<br />
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SNP: rs397514576,
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ClinVar: RCV000032964
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a study of 250 patients with Alstrom syndrome (ALMS; 203800), Marshall et al. (2007) identified 2 alleles carrying a 10945G-T transversion in exon 16 of the ALMS1 gene, resulting in a glu3649-to-ter (E3649X) substitution. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
|
In members of a large consanguineous Saudi Arabian family who had been diagnosed with Leber congenital amaurosis (LCA; see 204000), Wang et al. (2011) identified homozygosity for the E3649X mutation in the ALMS1 gene. The authors stated that no other syndromic features such as hearing loss or obesity had been reported in the Saudi Arabian patients. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>REFERENCES</strong>
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</span>
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</h4>
|
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<div>
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<p />
|
|
</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
|
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Collin, G. B., Cyr, E., Bronson, R., Marshall, J. D., Gifford, E. J., Hicks, W., Murray, S. A., Zheng, Q. Y., Smith, R. S., Nishina, P. M., Naggert, J. K.
|
|
<strong>Alms1-disrupted mice recapitulate human Alstrom syndrome.</strong>
|
|
Hum. Molec. Genet. 14: 2323-2333, 2005.
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[PubMed: 16000322]
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[Full Text: https://doi.org/10.1093/hmg/ddi235]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Collin, G. B., Marshall, J. D., Boerkoel, C. F., Levin, A. V., Weksberg, R., Greenberg, J., Michaud, J. L., Naggert, J. K., Nishina, P. M.
|
|
<strong>Alstrom syndrome: further evidence for linkage to human chromosome 2p13.</strong>
|
|
Hum. Genet. 105: 474-479, 1999.
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[PubMed: 10598815]
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[Full Text: https://doi.org/10.1007/s004390051133]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Collin, G. B., Marshall, J. D., Cardon, L. R., Nishina, P. M.
|
|
<strong>Homozygosity mapping of Alstrom syndrome to chromosome 2p.</strong>
|
|
Hum. Molec. Genet. 6: 213-219, 1997.
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[PubMed: 9063741]
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[Full Text: https://doi.org/10.1093/hmg/6.2.213]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Collin, G. B., Marshall, J. D., Ikeda, A., So, W. V., Russell-Eggitt, I., Maffei, P., Beck, S., Boerkoel, C. F., Sicolo, N., Martin, M., Nishina, P. M., Naggert, J. K.
|
|
<strong>Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome.</strong>
|
|
Nature Genet. 31: 74-78, 2002.
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|
|
[PubMed: 11941369]
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[Full Text: https://doi.org/10.1038/ng867]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Hearn, T., Renforth, G. L., Spalluto, C., Hanley, N. A., Piper, K., Brickwood, S., White, C., Connolly, V., Taylor, J. F. N., Russell-Eggitt, I., Bonneau, D., Walker, M., Wilson, D. I.
|
|
<strong>Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alstrom syndrome.</strong>
|
|
Nature Genet. 31: 79-83, 2002.
|
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|
|
[PubMed: 11941370]
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[Full Text: https://doi.org/10.1038/ng874]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Knorz, V. J., Spalluto, C., Lessard, M., Purvis, T. L., Adigun, F. F., Collin, G. B., Hanley, N. A., Wilson, D. I., Hearn, T.
|
|
<strong>Centriolar association of ALMS1 and likely centrosomal functions of the ALMS motif-containing proteins C10orf90 and KIAA1731.</strong>
|
|
Molec. Biol. Cell 21: 3617-3629, 2010.
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[PubMed: 20844083]
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[Full Text: https://doi.org/10.1091/mbc.E10-03-0246]
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Li, G., Vega, R., Nelms, K., Gekakis, N., Goodnow, C., McNamara, P., Wu, H., Hong, N. A., Glynne, R.
|
|
<strong>A role for Alstrom syndrome protein, Alms1, in kidney ciliogenesis and cellular quiescence.</strong>
|
|
PLoS Genet. 3: e8, 2007. Note: Electronic Article.
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|
|
[PubMed: 17206865]
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|
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[Full Text: https://doi.org/10.1371/journal.pgen.0030008]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Macari, F., Lautier, C., Girardet, A., Dadoun, F., Darmon, P., Dutour, A., Renard, E., Bouvagnet, P., Claustres, M., Oliver, C., Grigorescu, F.
|
|
<strong>Refinement of genetic localization of the Alstrom syndrome on chromosome 2p12-13 by linkage analysis in a North African family.</strong>
|
|
Hum. Genet. 103: 658-661, 1998.
|
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|
|
[PubMed: 9921899]
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[Full Text: https://doi.org/10.1007/s004390050887]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Marshall, J. D., Hinman, E. G., Collin, G. B., Beck, S., Cerqueira, R., Maffei, P., Milan, G., Zhang, W., Wilson, D. I., Hearn, T., Tavares, P., Vettor, R., Veronese, C., Martin, M., So, W. V., Nishina, P. M., Naggert, J. K.
|
|
<strong>Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alstrom syndrome.</strong>
|
|
Hum. Mutat. 28: 1114-1123, 2007.
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|
|
[PubMed: 17594715]
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[Full Text: https://doi.org/10.1002/humu.20577]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Marshall, J. D., Ludman, M. D., Shea, S. E., Salisbury, S. R., Willi, S. M., LaRoche, R. G., Nishina, P. M.
|
|
<strong>Genealogy, natural history, and phenotype of Alstrom syndrome in a large Acadian kindred and three additional families.</strong>
|
|
Am. J. Med. Genet. 73: 150-161, 1997.
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|
|
[PubMed: 9409865]
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[Full Text: https://doi.org/10.1002/(sici)1096-8628(19971212)73:2<150::aid-ajmg9>3.0.co;2-y]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Nagase, T., Ishikawa, K., Nakajima, D., Ohira, M., Seki, N., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O.
|
|
<strong>Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.</strong>
|
|
DNA Res. 4: 141-150, 1997.
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|
[PubMed: 9205841]
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[Full Text: https://doi.org/10.1093/dnares/4.2.141]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Ozgul, R. K., Satman, I., Collin, G. B., Hinman, E. G., Marshall, J. D., Kocaman, O., Tutuncu, Y., Yilmaz, T., Naggert, J. K.
|
|
<strong>Molecular analysis and long-term clinical evaluation of three siblings with Alstrom syndrome.</strong>
|
|
Clin. Genet. 72: 351-356, 2007.
|
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|
|
[PubMed: 17850632]
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|
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[Full Text: https://doi.org/10.1111/j.1399-0004.2007.00848.x]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Taskesen, M., Collin, G. B., Evsikov, A. V., Guzel, A., Ozgul, R. K., Marshall, J. D., Naggert, J. K.
|
|
<strong>Novel Alu retrotransposon insertion leading to Alstrom syndrome.</strong>
|
|
Hum. Genet. 131: 407-413, 2012.
|
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|
|
|
[PubMed: 21877133]
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|
|
[Full Text: https://doi.org/10.1007/s00439-011-1083-9]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Wang, X., Wang, H., Cao, M., Li, Z., Chen, X., Patenia, C., Gore, A., Abboud, E. B., Al-Rajhi, A. A., Lewis, R. A., Lupski, J. R., Mardon, G., Zhang, K., Muzny, D., Gibbs, R. A., Chen, R.
|
|
<strong>Whole-exome sequencing identifies ALMS1, IQCB1, CNGA3, and MYO7A mutations in patients with Leber congenital amaurosis.</strong>
|
|
Hum. Mutat. 32: 1450-1459, 2011.
|
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|
|
|
|
[PubMed: 21901789]
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|
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[Full Text: https://doi.org/10.1002/humu.21587]
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</p>
|
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</li>
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</ol>
|
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<div>
|
|
<br />
|
|
</div>
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</div>
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</div>
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<div>
|
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<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
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<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</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">
|
|
Patricia A. Hartz - updated : 10/18/2017<br>Marla J. F. O'Neill - updated : 11/2/2012<br>Marla J. F. O'Neill - updated : 10/1/2012<br>George E. Tiller - updated : 1/9/2009<br>Cassandra L. Kniffin - updated : 1/8/2008<br>Cassandra L. Kniffin - updated : 11/14/2007<br>Patricia A. Hartz - updated : 8/8/2007
|
|
</span>
|
|
</div>
|
|
</div>
|
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
|
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<div class="row">
|
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
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<span class="text-nowrap mim-text-font">
|
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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">
|
|
Victor A. McKusick : 4/10/2002
|
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</span>
|
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</div>
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</div>
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</div>
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<div>
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<br />
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<div>
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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Edit History:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 11/01/2019<br>carol : 10/31/2019<br>alopez : 10/18/2017<br>carol : 08/17/2015<br>mcolton : 6/11/2015<br>carol : 11/2/2012<br>carol : 10/2/2012<br>terry : 10/1/2012<br>wwang : 1/9/2009<br>wwang : 1/28/2008<br>ckniffin : 1/8/2008<br>wwang : 12/14/2007<br>ckniffin : 11/14/2007<br>mgross : 8/13/2007<br>terry : 8/8/2007<br>terry : 3/24/2004<br>alopez : 6/7/2002<br>alopez : 4/10/2002<br>alopez : 4/10/2002
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